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Exercise Biochemistry
496 Pages
Exercise Biochemistry brings an admittedly difficult and technical subject to life. Extremely user- and student-friendly, it is written in conversational style by Vassilis Mougios, who poses and then answers questions as if in conversation with a student. Mougios does an excellent job of making the information interesting by using simple language without compromising scientific accuracy and content. He also uses ample analogies, related works of art, and numerous illustrations to drive home his points for readers.
The result is that Exercise Biochemistry is a highly informative and illuminating text on the effects of exercise on molecular-level functioning. It presents the basics of biochemistry as well as in-depth coverage of exercise biochemistry. The book uses key terms, sidebars, and questions and problems posed at the end of each chapter to facilitate learning. It also covers metabolism, endocrinology, and assessment all in one volume, unlike other exercise biochemistry books.
In exploring all of these topics, Exercise Biochemistry makes the case for exercise biochemistry to have a stand-alone textbook. In fact, this book will encourage more universities to introduce exercise biochemistry courses to their curricula. Having the necessary topics of basic biochemistry in a single volume will facilitate the work of both instructors and students.
Exercise Biochemistry will also be useful to graduate students in sport science who have not been formally introduced to exercise biochemistry during their undergraduate programs. Additionally, it can supplement exercise physiology textbooks with its coverage of the molecular basis of physiological processes. This book is also for physical education and sport professionals who have an interest in how the human body functions during and after exercise. And this book is addressed to health scientists who are interested in the transformations in human metabolism brought about by physical activity.
The book is organized in four parts. Part I introduces readers to biochemistry basics, including chapters on metabolism, proteins, nucleic acids and gene expression, and carbohydrates and lipids. Part II consists of two chapters that explore neural control of movement and muscle contraction. The essence of the book is found in part III, which details exercise metabolism in its six chapters. Included are chapters on carbohydrate, lipid, and protein metabolism in exercise; compounds of high phosphoryl transfer potential; effects of exercise on gene expression; and integration of exercise metabolism. In part IV, the author focuses on biochemical assessment of people who exercise, with chapters on iron status, metabolites, and enzymes and hormones. Simple biochemical tests are provided to assess an athlete's health and performance.
Exercise Biochemistry is a highly readable book that serves as a source for understanding how exercise changes bodily functions. The text is useful for both students and practitioners alike.
Contents
Preface
A Guided Tour for the Student
Part I Biochemistry Basics
Chapter 1 Introduction
-1.1 Chemical Elements
-1.2 Chemical Bonds
-1.3 Molecules
-1.4 Ions
-1.5 Polarity Influences Miscibility
-1.6 Solutions
-1.7 Chemical Reactions and Equilibrium
-1.8 pH
-1.9 Acid-Base Interconversions
-1.10 Classes of Biological Substances
-1.11 Cell Structure
-Problems and Critical Thinking Questions
Chapter 2 Metabolism
-2.1 Free-Energy Changes Earmark Metabolic Reactions
-2.2 Determinants of Free-Energy Change
-2.3 ATP, the Energy Currency of Cells
-2.4 Phases of Metabolism
-2.5 Oxidation-Reduction Reactions
-2.6 Overview of Catabolism
-Problems and Critical Thinking Questions
Chapter 3 Proteins
-3.1 Amino Acids
-3.2 The Peptide Bond
-3.3 Primary Structure of Proteins
-3.4 Secondary Structure
-3.5 Tertiary Structure
-3.6 Denaturation
-3.7 Quaternary Structure
-3.8 Protein Function
-3.9 Oxygen Carriers
-3.10 Myoglobin
-3.11 Hemoglobin
-3.12 The Wondrous Properties of Hemoglobin
-3.13 Enzymes
-3.14 The Active Site
-3.15 Enzymes Affect the Rate but not the Direction of Reactions
-3.16 Factors Affecting the Rate of Enzyme Reactions
-Problems and Critical Thinking Questions
Chapter 4 Nucleic Acids and Gene Expression
-4.1 Introducing Nucleic Acids
-4.2 Flow of Genetic Information
-4.3 Deoxyribonucleotides, the Building Blocks of DNA
-4.4 Primary Structure of DNA
-4.5 The Double Helix of DNA
-4.6 The Genome of Living Organisms
-4.7 DNA Replication
-4.8 Mutations
-4.9 RNA
-4.10 Transcription
-4.11 Genes and Gene Expression
-4.12 Messenger RNA
-4.13 Translation
-4.14 The Genetic Code
-4.15 Transfer RNA
-4.16 Translation Continued
-4.17 In The Beginning, RNA?
-Problems and Critical Thinking Questions
Chapter 5 Carbohydrates and Lipids
-5.1 Carbohydrates
-5.2 Monosaccharides
-5.3 Oligosaccharides
-5.4 Polysaccharides
-5.5 Lipids
-5.6 Fatty Acids
-5.7 Triacylglycerols
-5.8 Phospholipids
-5.9 Steroids
-5.10 Cell Membranes
-Problems and Critical Thinking Questions
Part I Summary
Part II Biochemistry of the Neural and Muscular Processes of Movement
Chapter 6 Neural Control of Movement
-6.1 Nerve Signals Are Transmitted in Two Ways
-6.2 The Resting Potential
-6.3 The Action Potential
-6.4 Propagation of an Action Potential
-6.5 Transmission of a Nerve Impulse from One Neuron to Another
-6.6 Birth of a Nerve Impulse
-6.7 The Neuromuscular Junction
-6.8 A Lethal Arsenal at the Service of Research
-Problems and Critical Thinking Questions
Chapter 7 Muscle Contraction
-7.1 Structure of a Muscle Cell
-7.2 The Sliding-Filament Theory
-7.3 The Wondrous Properties of Myosin
-7.4 Structure of Myosin
-7.5 Actin
-7.6 Sarcomere Architecture
-7.7 Mechanism of Force Generation
-7.8 Myosin Isoforms and Muscle Fiber Types
-7.9 Control of Muscle Contraction
-7.10 Excitation-Contraction Coupling
-Problems and Critical Thinking Questions
Part II Summary
Part III Exercise Metabolism
III.1 Principles of Exercise Metabolism
III.2 Exercise Parameters
III.3 Experimental Models Used to Study Exercise Metabolism
III.4 Five Means of Metabolic Control in Exercise
III.5 Four Classes of Energy Sources in Exercise
Chapter 8 Compounds of High Phosphoryl Transfer Potential
-8.1 The ATP-ADP Cycle
-8.2 The ATP-ADP Cycle in Exercise
-8.3 Creatine Phosphate
-8.4 Window to the Sarcoplasm
-8.5 Loss of AMP by Deamination
-Problems and Critical Thinking Questions
Chapter 9 Carbohydrate Metabolism in Exercise
-9.1 Glycogen Metabolism
-9.2 Exercise Speeds up Glycogenolysis in Muscle
-9.3 The Cyclic-AMP Cascade
-9.4 Recapping the Effect of Exercise on Glycogen Metabolism
-9.5 Glycolysis
-9.6 Exercise Speeds up Glycolysis in Muscle
-9.7 Pyruvate Oxidation
-9.8 Exercise Speeds up Pyruvate Oxidation in Muscle
-9.9 The Citric Acid Cycle
-9.10 Exercise Speeds up the Citric Acid Cycle in Muscle
-9.11 The Electron Transport Chain
-9.12 Oxidative Phosphorylation
-9.13 Energy Yield of the Electron Transport Chain
-9.14 Energy Yield of Carbohydrate Oxidation
-9.15 Exercise Speeds up Oxidative Phosphorylation in Muscle
-9.16 Lactate Production in Muscle During Exercise
-9.17 Features of the Anaerobic Carbohydrate Catabolism
-9.18 Utilizing Lactate
-9.19 Gluconeogenesis
-9.20 Exercise Speeds up Gluconeogenesis in the Liver
-9.21 The Cori Cycle
-9.22 Exercise Speeds up Glycogenolysis in the Liver
-9.23 Control of the Plasma Glucose Concentration in Exercise
-9.24 Blood Lactate Accumulation
-9.25 Blood Lactate Removal
-9.26 “Thresholds”
Problems and Critical Thinking Questions
Chapter 10 Lipid Metabolism in Exercise
-10.1 Triacylglycerol Metabolism in Adipose Tissue
-10.2 Exercise Speeds up Lipolysis
-10.3 Fate of the Lipolytic Products During Exercise
-10.4 Fatty Acid Degradation
-10.5 Energy Yield of Fatty Acid Oxidation
-10.6 Fatty Acid Synthesis
-10.7 Exercise Speeds up Fatty Acid Oxidation in Muscle
-10.8 Changes in the Plasma Fatty Acid Concentration and Profile During Exercise
-10.9 Interconversion of Lipids and Carbohydrates
-10.10 Plasma Lipoproteins
-10.11 A Lipoprotein Odyssey
-10.12 Effects of Exercise on Plasma Triacylglycerols
-10.13 Effects of Exercise on Plasma Cholesterol
-10.14 Exercise Increases Ketone Body Formation
-Problems and Critical Thinking Questions
Chapter 11 Protein Metabolism in Exercise
-11.1 Protein Metabolism
-11.2 Effect of Exercise on Protein Metabolism
-11.3 Amino Acid Metabolism in Muscle During Exercise
-11.4 Amino Acid Metabolism in the Liver During Exercise
-11.5 The Urea Cycle
-11.6 Amino Acid Synthesis
-11.7 Plasma Amino Acid, Ammonia, and Urea Concentrations During Exercise
-11.8 Contribution of Proteins to the Energy Expenditure of Exercise
-11.9 Effects of Training on Protein Metabolism
-Critical Thinking Questions
Chapter 12 Effects of Exercise on Gene Expression
-12.1 Stages in the Control of Gene Expression
-12.2 Which Stages in the Control of Gene Expression Does Exercise Affect?
-12.3 Kinetics of a Gene Product After Exercise
-12.4 Exercise-Induced Changes that May Modify Gene Expression
-12.5 Mechanisms of Exercise-Induced Muscle Hypertrophy
-12.6 Mechanisms of Exercise-Induced Mitochondrial Biogenesis
-Problems and Critical Thinking Questions
Chapter 13 Integration of Exercise Metabolism
-13.1 Interconnections of Metabolic Pathways
-13.2 Energy Systems
-13.3 Energy Sources in Exercise
-13.4 Choice of Energy Sources During Exercise
-13.5 Effect of Exercise Intensity on the Choice of Energy Sources
-13.6 Effect of Exercise Duration on the Choice of Energy Sources
-13.7 Interaction of Duration and Intensity: Energy Sources in Running and Swimming
-13.8 Effect of the Exercise Program on the Choice of Energy Sources
-13.9 Effect of Heredity on the Choice of Energy Sources in Exercise
-13.10 Conversions of Muscle Fiber Types
-13.11 Effect of Nutrition on the Choice of Energy Sources During Exercise
-13.12 Adaptations of the Proportion of Energy Sources During Exercise to Endurance Training
-13.13 How Does Endurance Training Modify the Proportion of Energy Sources During Exercise?
-13.14 Adaptations of Energy Metabolism to Anaerobic Training
-13.15 Effect of Age on the Choice of Energy Sources During Exercise
-13.16 Do Sex and Ambient Temperature Affect the Choice of Energy Sources During Exercise?
-13.17 The Proportion of Fuels Can Be Measured Bloodlessly
-13.18 Hormonal Effects on Exercise Metabolism
-13.19 Fatigue
-13.20 Central Fatigue
-13.21 Peripheral Fatigue
-13.22 Restoration of the Energy State After Exercise
-13.23 Metabolic Changes in Detraining
-Problems and Critical Thinking Questions
Part III Summary
Part IV Biochemical Assessment of Exercising Persons
IV.1 The Blood
IV.2 Aims and Scope of the Biochemical Assessment
IV.3 The Reference Interval
IV.4 Classes of Biochemical Parameters
Chapter 14 Iron Status
-14.1 Hemoglobin
-14.2 Hematologic Parameters
-14.3 Does Sports Anemia Exist?
-14.4 Iron
-14.5 Total Iron-Binding Capacity
-14.6 Transferrin Saturation
-14.7 Soluble Transferrin Receptor
-14.8 Ferritin
-14.9 Iron Deficiency
-Problems and Critical Thinking Questions
Chapter 15 Metabolites
-15.1 Lactate
-15.2 Estimating the Anaerobic Lactic Capacity
-15.3 Programming Training
-15.4 Estimating Aerobic Endurance
-15.5 Glucose
-15.6 Triacylglycerols
-15.7 Cholesterol
-15.8 HDL Cholesterol
-15.9 LDL Cholesterol
-15.10 Recapping Cholesterol
-15.11 Glycerol
-15.12 Urea
-15.13 Ammonia
-15.14 Creatinine
-Problems and Critical Thinking Questions
Chapter 16 Enzymes and Hormones
-16.1 Enzymes
-16.2 Creatine Kinase
-16.3 Aminotransferases
-16.4 Steroid Hormones
-16.5 Cortisol
-16.6 Testosterone
-16.7 Overtraining
-16.8 Epilogue
-Problems and Critical Thinking Questions
Part IV Summary
References
Suggested Readings
Answers to Problems and Critical Thinking Questions
Glossary
Index
About the Author
Vassilis Mougios, PhD, is a professor of exercise biochemistry and director of the Laboratory of Evaluation of Human Biological Performance at the University of Thessaloniki in Greece. A teacher of exercise biochemistry, sport nutrition, and ergogenic aspects of sport for 30 years, Mougios served on the Scientific Committee of the 2004 Pre-Olympic Congress. He has coauthored many articles in international scientific journals and has done research on muscle contraction, exercise metabolism, biochemical assessment of athletes, and sport nutrition.
Mougios is a member of the American College of Sports Medicine and the American Physiological Society. He is a fellow and member of the reviewing panel of the European College of Sport Science. He serves as a topic editor for Frontiers in Physiology and a reviewer for Journal of Applied Physiology, British Journal of Sports Medicine, European Journal of Clinical Nutrition, Acta Physiologica, Annals of Nutrition and Metabolism, Metabolism, and Obesity. In his leisure time, he enjoys rafting, hiking, and photography.
Adaptations of the Vasculature to Training
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol.
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol. On top of these effects, endurance training contributes to lowering the risk of atherosclerosis by increasing HDL cholesterol.
In addition, the increases in blood flow and pressure accompanying exercise cause structural and functional adaptations of the vascular wall that lower the risk of atherosclerosis. These beneficial effects seem to be mediated by the endothelium, the single layer of cells lining the interior surface of the blood vessels, in direct contact with blood on the inside and surrounded by smooth muscle cells on the outside (figure 15.3).
Figure 15.3 How exercise elicits vasodilation. The increase in the pumping activity of the heart during exercise augments the shear stress on the endothelial cells lining the blood vessels. This mechanical stimulus leads to activation of eNOS, which catalyzes the synthesis of NO from arginine. NO diffuses to the smooth muscle cells forming the walls of blood vessels and activates soluble guanylate cyclase, which catalyzes the synthesis of cyclic GMP (cGMP) from GTP. Cyclic GMP activates PKG, leading to a drop in the cytosolic Ca2+ concentration, relaxation of the smooth muscle cells, and vasodilation.
The endothelial cells possess a variety of proteins that convert the mechanical stimulus of the exercise-induced increase in shear stress into chemical signals. In turn, these signals activate endothelial nitrogen oxide synthase (eNOS). This enzyme catalyzes the synthesis of nitric oxide (introduced in section 1.5) from arginine and oxygen in a reaction requiring NADPH as a reductant and yielding citrulline (the intermediate compound of the urea cycle introduced in section 12.9 and figure 12.10) in addition to NO.
NO diffuses out of the endothelial cells and enters neighboring smooth muscle cells, where it activates soluble guanylate cyclase, a cytosolic enzyme that catalyzes the formation of cyclic guanylate, or cyclic GMP (cGMP), from GTP, in a manner analogous to the synthesis of cAMP (section 10.6 and reaction 10.5).
Cyclic GMP, in turn, activates cGMP-dependent protein kinase, or PKG, which promotes smooth muscle relaxation by activating an ion pump that removes Ca2+ from the cytosol, thus preventing the interaction of myosin and actin. (Ca2+ allows myosin binding to actin in smooth muscle cells and skeletal muscle fibers through a series of interactions differing from the one described in section 8.10.) Smooth muscle relaxation results in dilation of the blood vessels, or vasodilation. The capacity of the vessels to dilate in response to increased blood flow, a property termed flow-mediated dilation, is considered an index of cardiovascular health.
As Green and coworkers review, training improves flow-mediated dilation—especially in individuals with or at risk of CVD—and reduces arterial wall stiffness by enhancing the endothelium-dependent signal transduction pathway described earlier. The enhancement includes higher eNOS content or activity. It is also possible that training influences other pathways of flow-mediated dilation. In addition, training increases the diameter of vessels—such as the coronary arteries, as well as arteries that nourish the exercising limbs—thus supplying more blood where it is needed. The stimulus, again, appears to be the increased shear stress imposed by blood on the endothelium with exercise.
Finally, training influences the smaller blood vessels: It increases the amount and diameter of the arterioles (the branches of arteries leading to capillaries) and muscle capillarization. The latter is measured as either the total number of capillaries in a muscle, or the number of capillaries per muscle fiber, or capillary density (defined in section 14.15 as the number of capillaries per unit of muscle cross-sectional area). Increased capillarization enhances the delivery of nutrients and O2 to muscle, as well as the uptake of muscle CO2 by blood.
Training-induced capillarization may be due to increased blood flow or to muscle activity itself. Both factors may promote the release of vascular endothelial growth factor (VEGF), a key angiogenic (that is, vessel-generating) protein, from muscle fibers. VEGF binds to the VEGF receptor in the plasma membrane of endothelial cells and activates a variety of signal transduction pathways, leading to endothelial cell proliferation and, hence, formation of new capillaries.
You can see that training provides more than one way of increasing blood supply to the active muscles. It seems that these beneficial adaptations can be elicited by endurance, resistance, and interval training. Improvements in vascular function with training are evident in both healthy humans and (possibly more evident) humans with or at risk of CVD.
Control of Muscle Activity by Ca2+
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered.
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered. Today we know that Ca2+ controls muscle activity and that it does so by permitting the binding of myosin to F-actin. This action of Ca2+ is not direct but indirect. As the Japanese physiologist Setsuro Ebashi discovered in the 1960s, control is exerted through tropomyosin and troponin, the two proteins that coexist with actin in the thin filaments, constituting about one third of the thin-filament mass. Let's meet them.
Tropomyosin has a molecular mass of 70 kDa and consists of two similar stringlike subunits in -helical conformation. The two subunits wind around each other just as the myosin heavy chains do in the myosin tail. The resulting extremely long tropomyosin molecules join in a row to form fibers. Two such fibers run along each thin filament while following the twisting of the actin monomers (figure 8.11).
Figure 8.11 Thin-filament proteins. A thin filament consists of an F-actin fiber (the double necklace of figure 8.7), two series of tropomyosin molecules, and troponin (Tn) complexes placed at regular intervals. Each troponin complex consists of TnC, which is the Ca2+ acceptor; TnI, which binds to actin; and TnT, which extends by way of a long tail along tropomyosin.
Adapted from L. Smillie and S. Ebashi, Essays in Biochemistry, vol. 10, edited by P.N. Campbell and F. Dickens (Orlando, FL: Academic, 1974), 1-35; C. Cohen Scientific America 233 (1975): 36 - 45. Courtesy of L. Smillie.
Troponin, symbolized as Tn, is a complex of three different subunits: TnC (18 kDa), TnI (24 kDa), and TnT (37 kDa). TnC binds Ca2+, TnI binds to actin, and TnT binds to tropomyosin. Two troponin complexes appear on the two sides of a thin filament every 39 nm, which is approximately the length of a tropomyosin molecule. One troponin complex attached to one tropomyosin molecule controls approximately seven actin monomers.
When a muscle is at rest (relaxed), the cytosol has a very low [Ca2+], approximately 10-7 mol · L-1. Researchers believe that, in this case, interactions among F-actin, TnI, TnT, and tropomyosin hold the latter close to the sites on the actin monomers where the myosin heads bind. Thus, tropomyosin hinders the interaction of thin and thick filaments. As we will see in the next section, muscle excitation by the nervous system results in the release of Ca2+ from an intracellular reservoir called the sarcoplasmic reticulum. This release causes a 100-fold surge in the cytosolic [Ca2+], from 10-7 to 10-5 mol · L-1.
The increased Ca2+ ions encounter TnC, bind to it, and elicit a change in its conformation. As a result, TnC detaches TnI from F-actin. This detachment lets tropomyosin move over the surface of the thin filament, away from the binding sites of myosin on F-actin. Myosin then binds to F-actin, and the muscle contracts. In fact, there is evidence that myosin binding to F-actin is cooperative; that is, the binding of some myosin heads facilitates the binding of additional ones by promoting the displacement of tropomyosin. This effect is reminiscent of the cooperative binding of O2 to hemoglobin (section 3.12).
Muscle activity continues until Ca2+ is sequestered in the sarcoplasmic reticulum (in a manner that we will examine shortly). The actin-TnI-TnT-tropomyosin interaction is then restored. Tropomyosin returns to a position hindering cross-bridge formation, and the muscle relaxes. The chain of events through which Ca2+ controls muscle contraction is summarized in figure 8.12.
Figure 8.12 Control of muscle contraction and relaxation by Ca2+. Ca2+ controls muscle contraction (left) and relaxation (right) through a series of protein interactions triggered by, respectively, Ca2+ release from and sequestration in the sarcoplasmic reticulum and involving troponin, tropomyosin, actin, and myosin.
What are triacylglycerols, and how do they serve us?
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils.
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils. Because of this abundance, they constitute 90% to 95% of dietary fat. In both animals and plants, triacylglycerols serve mainly as energy depots.
A triacylglycerol consists of a glycerol unit and three fatty acid units. Glycerol (figure 5.12), also known as glycerin or glycerine, is a compound of three carbons and three hydroxyl groups, each of which connects with the carboxyl group of a fatty acid to form an ester linkage. Thus, every triacylglycerol (figure 5.12) contains three ester linkages, which makes it a triester.
Figure 5.12 Glycerol and triacylglycerol. Triacylglycerols, the largest energy depot in living organisms, are triesters of glycerol and fatty acids. R1, R2, and R3 represent the aliphatic chains of the fatty acids, which usually differ. Acyl groups are shown in color.
Because there is a great variety of available fatty acids, and because any of them can be linked to any of the hydroxyl groups of glycerol, we end up with an even greater variety of triacylglycerols. Chances are that there will be both saturated and unsaturated fatty acids present in a single triacylglycerol. Therefore, it is not accurate to state that a certain food contains only saturated or unsaturated fat. Instead, one should state that a certain food contains primarily saturated or unsaturated fatty acids.
Triacylglycerols are hydrophobic, which is evident by the immiscibility of fats or oils with water. Moreover, triacylglycerols have low thermal conductivity, rendering the subcutaneous fat of animals an efficient insulator of their internal organs against cold exposure.
The part of a fatty acid connected to an oxygen of glycerol in a triacylglycerol is called an acyl group. This is where the term tri-acyl-glycerol comes from; hence it is more accurate than triglyceride. The acyl groups derive from the ion of a fatty acid by removal of O-, and they bear the name of the fatty acid with the ending -oyl in place of -ate. Thus, the acyl group of palmitate is called the palmitoyl group.
The difference in melting point between saturated and unsaturated fatty acids described in the previous section is reflected in triacylglycerols: The more saturated acyl groups they contain, the higher their melting point is. Triacylglycerols of animal origin have a high content of saturated acyl groups, which is why animal fat is solid at room temperature. Conversely, plant triacylglycerols have a high content of unsaturated acyl groups, which is why vegetable oils are liquid in the same conditions.
Adaptations of the Vasculature to Training
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol.
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol. On top of these effects, endurance training contributes to lowering the risk of atherosclerosis by increasing HDL cholesterol.
In addition, the increases in blood flow and pressure accompanying exercise cause structural and functional adaptations of the vascular wall that lower the risk of atherosclerosis. These beneficial effects seem to be mediated by the endothelium, the single layer of cells lining the interior surface of the blood vessels, in direct contact with blood on the inside and surrounded by smooth muscle cells on the outside (figure 15.3).
Figure 15.3 How exercise elicits vasodilation. The increase in the pumping activity of the heart during exercise augments the shear stress on the endothelial cells lining the blood vessels. This mechanical stimulus leads to activation of eNOS, which catalyzes the synthesis of NO from arginine. NO diffuses to the smooth muscle cells forming the walls of blood vessels and activates soluble guanylate cyclase, which catalyzes the synthesis of cyclic GMP (cGMP) from GTP. Cyclic GMP activates PKG, leading to a drop in the cytosolic Ca2+ concentration, relaxation of the smooth muscle cells, and vasodilation.
The endothelial cells possess a variety of proteins that convert the mechanical stimulus of the exercise-induced increase in shear stress into chemical signals. In turn, these signals activate endothelial nitrogen oxide synthase (eNOS). This enzyme catalyzes the synthesis of nitric oxide (introduced in section 1.5) from arginine and oxygen in a reaction requiring NADPH as a reductant and yielding citrulline (the intermediate compound of the urea cycle introduced in section 12.9 and figure 12.10) in addition to NO.
NO diffuses out of the endothelial cells and enters neighboring smooth muscle cells, where it activates soluble guanylate cyclase, a cytosolic enzyme that catalyzes the formation of cyclic guanylate, or cyclic GMP (cGMP), from GTP, in a manner analogous to the synthesis of cAMP (section 10.6 and reaction 10.5).
Cyclic GMP, in turn, activates cGMP-dependent protein kinase, or PKG, which promotes smooth muscle relaxation by activating an ion pump that removes Ca2+ from the cytosol, thus preventing the interaction of myosin and actin. (Ca2+ allows myosin binding to actin in smooth muscle cells and skeletal muscle fibers through a series of interactions differing from the one described in section 8.10.) Smooth muscle relaxation results in dilation of the blood vessels, or vasodilation. The capacity of the vessels to dilate in response to increased blood flow, a property termed flow-mediated dilation, is considered an index of cardiovascular health.
As Green and coworkers review, training improves flow-mediated dilation—especially in individuals with or at risk of CVD—and reduces arterial wall stiffness by enhancing the endothelium-dependent signal transduction pathway described earlier. The enhancement includes higher eNOS content or activity. It is also possible that training influences other pathways of flow-mediated dilation. In addition, training increases the diameter of vessels—such as the coronary arteries, as well as arteries that nourish the exercising limbs—thus supplying more blood where it is needed. The stimulus, again, appears to be the increased shear stress imposed by blood on the endothelium with exercise.
Finally, training influences the smaller blood vessels: It increases the amount and diameter of the arterioles (the branches of arteries leading to capillaries) and muscle capillarization. The latter is measured as either the total number of capillaries in a muscle, or the number of capillaries per muscle fiber, or capillary density (defined in section 14.15 as the number of capillaries per unit of muscle cross-sectional area). Increased capillarization enhances the delivery of nutrients and O2 to muscle, as well as the uptake of muscle CO2 by blood.
Training-induced capillarization may be due to increased blood flow or to muscle activity itself. Both factors may promote the release of vascular endothelial growth factor (VEGF), a key angiogenic (that is, vessel-generating) protein, from muscle fibers. VEGF binds to the VEGF receptor in the plasma membrane of endothelial cells and activates a variety of signal transduction pathways, leading to endothelial cell proliferation and, hence, formation of new capillaries.
You can see that training provides more than one way of increasing blood supply to the active muscles. It seems that these beneficial adaptations can be elicited by endurance, resistance, and interval training. Improvements in vascular function with training are evident in both healthy humans and (possibly more evident) humans with or at risk of CVD.
Control of Muscle Activity by Ca2+
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered.
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered. Today we know that Ca2+ controls muscle activity and that it does so by permitting the binding of myosin to F-actin. This action of Ca2+ is not direct but indirect. As the Japanese physiologist Setsuro Ebashi discovered in the 1960s, control is exerted through tropomyosin and troponin, the two proteins that coexist with actin in the thin filaments, constituting about one third of the thin-filament mass. Let's meet them.
Tropomyosin has a molecular mass of 70 kDa and consists of two similar stringlike subunits in -helical conformation. The two subunits wind around each other just as the myosin heavy chains do in the myosin tail. The resulting extremely long tropomyosin molecules join in a row to form fibers. Two such fibers run along each thin filament while following the twisting of the actin monomers (figure 8.11).
Figure 8.11 Thin-filament proteins. A thin filament consists of an F-actin fiber (the double necklace of figure 8.7), two series of tropomyosin molecules, and troponin (Tn) complexes placed at regular intervals. Each troponin complex consists of TnC, which is the Ca2+ acceptor; TnI, which binds to actin; and TnT, which extends by way of a long tail along tropomyosin.
Adapted from L. Smillie and S. Ebashi, Essays in Biochemistry, vol. 10, edited by P.N. Campbell and F. Dickens (Orlando, FL: Academic, 1974), 1-35; C. Cohen Scientific America 233 (1975): 36 - 45. Courtesy of L. Smillie.
Troponin, symbolized as Tn, is a complex of three different subunits: TnC (18 kDa), TnI (24 kDa), and TnT (37 kDa). TnC binds Ca2+, TnI binds to actin, and TnT binds to tropomyosin. Two troponin complexes appear on the two sides of a thin filament every 39 nm, which is approximately the length of a tropomyosin molecule. One troponin complex attached to one tropomyosin molecule controls approximately seven actin monomers.
When a muscle is at rest (relaxed), the cytosol has a very low [Ca2+], approximately 10-7 mol · L-1. Researchers believe that, in this case, interactions among F-actin, TnI, TnT, and tropomyosin hold the latter close to the sites on the actin monomers where the myosin heads bind. Thus, tropomyosin hinders the interaction of thin and thick filaments. As we will see in the next section, muscle excitation by the nervous system results in the release of Ca2+ from an intracellular reservoir called the sarcoplasmic reticulum. This release causes a 100-fold surge in the cytosolic [Ca2+], from 10-7 to 10-5 mol · L-1.
The increased Ca2+ ions encounter TnC, bind to it, and elicit a change in its conformation. As a result, TnC detaches TnI from F-actin. This detachment lets tropomyosin move over the surface of the thin filament, away from the binding sites of myosin on F-actin. Myosin then binds to F-actin, and the muscle contracts. In fact, there is evidence that myosin binding to F-actin is cooperative; that is, the binding of some myosin heads facilitates the binding of additional ones by promoting the displacement of tropomyosin. This effect is reminiscent of the cooperative binding of O2 to hemoglobin (section 3.12).
Muscle activity continues until Ca2+ is sequestered in the sarcoplasmic reticulum (in a manner that we will examine shortly). The actin-TnI-TnT-tropomyosin interaction is then restored. Tropomyosin returns to a position hindering cross-bridge formation, and the muscle relaxes. The chain of events through which Ca2+ controls muscle contraction is summarized in figure 8.12.
Figure 8.12 Control of muscle contraction and relaxation by Ca2+. Ca2+ controls muscle contraction (left) and relaxation (right) through a series of protein interactions triggered by, respectively, Ca2+ release from and sequestration in the sarcoplasmic reticulum and involving troponin, tropomyosin, actin, and myosin.
What are triacylglycerols, and how do they serve us?
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils.
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils. Because of this abundance, they constitute 90% to 95% of dietary fat. In both animals and plants, triacylglycerols serve mainly as energy depots.
A triacylglycerol consists of a glycerol unit and three fatty acid units. Glycerol (figure 5.12), also known as glycerin or glycerine, is a compound of three carbons and three hydroxyl groups, each of which connects with the carboxyl group of a fatty acid to form an ester linkage. Thus, every triacylglycerol (figure 5.12) contains three ester linkages, which makes it a triester.
Figure 5.12 Glycerol and triacylglycerol. Triacylglycerols, the largest energy depot in living organisms, are triesters of glycerol and fatty acids. R1, R2, and R3 represent the aliphatic chains of the fatty acids, which usually differ. Acyl groups are shown in color.
Because there is a great variety of available fatty acids, and because any of them can be linked to any of the hydroxyl groups of glycerol, we end up with an even greater variety of triacylglycerols. Chances are that there will be both saturated and unsaturated fatty acids present in a single triacylglycerol. Therefore, it is not accurate to state that a certain food contains only saturated or unsaturated fat. Instead, one should state that a certain food contains primarily saturated or unsaturated fatty acids.
Triacylglycerols are hydrophobic, which is evident by the immiscibility of fats or oils with water. Moreover, triacylglycerols have low thermal conductivity, rendering the subcutaneous fat of animals an efficient insulator of their internal organs against cold exposure.
The part of a fatty acid connected to an oxygen of glycerol in a triacylglycerol is called an acyl group. This is where the term tri-acyl-glycerol comes from; hence it is more accurate than triglyceride. The acyl groups derive from the ion of a fatty acid by removal of O-, and they bear the name of the fatty acid with the ending -oyl in place of -ate. Thus, the acyl group of palmitate is called the palmitoyl group.
The difference in melting point between saturated and unsaturated fatty acids described in the previous section is reflected in triacylglycerols: The more saturated acyl groups they contain, the higher their melting point is. Triacylglycerols of animal origin have a high content of saturated acyl groups, which is why animal fat is solid at room temperature. Conversely, plant triacylglycerols have a high content of unsaturated acyl groups, which is why vegetable oils are liquid in the same conditions.
Adaptations of the Vasculature to Training
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol.
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol. On top of these effects, endurance training contributes to lowering the risk of atherosclerosis by increasing HDL cholesterol.
In addition, the increases in blood flow and pressure accompanying exercise cause structural and functional adaptations of the vascular wall that lower the risk of atherosclerosis. These beneficial effects seem to be mediated by the endothelium, the single layer of cells lining the interior surface of the blood vessels, in direct contact with blood on the inside and surrounded by smooth muscle cells on the outside (figure 15.3).
Figure 15.3 How exercise elicits vasodilation. The increase in the pumping activity of the heart during exercise augments the shear stress on the endothelial cells lining the blood vessels. This mechanical stimulus leads to activation of eNOS, which catalyzes the synthesis of NO from arginine. NO diffuses to the smooth muscle cells forming the walls of blood vessels and activates soluble guanylate cyclase, which catalyzes the synthesis of cyclic GMP (cGMP) from GTP. Cyclic GMP activates PKG, leading to a drop in the cytosolic Ca2+ concentration, relaxation of the smooth muscle cells, and vasodilation.
The endothelial cells possess a variety of proteins that convert the mechanical stimulus of the exercise-induced increase in shear stress into chemical signals. In turn, these signals activate endothelial nitrogen oxide synthase (eNOS). This enzyme catalyzes the synthesis of nitric oxide (introduced in section 1.5) from arginine and oxygen in a reaction requiring NADPH as a reductant and yielding citrulline (the intermediate compound of the urea cycle introduced in section 12.9 and figure 12.10) in addition to NO.
NO diffuses out of the endothelial cells and enters neighboring smooth muscle cells, where it activates soluble guanylate cyclase, a cytosolic enzyme that catalyzes the formation of cyclic guanylate, or cyclic GMP (cGMP), from GTP, in a manner analogous to the synthesis of cAMP (section 10.6 and reaction 10.5).
Cyclic GMP, in turn, activates cGMP-dependent protein kinase, or PKG, which promotes smooth muscle relaxation by activating an ion pump that removes Ca2+ from the cytosol, thus preventing the interaction of myosin and actin. (Ca2+ allows myosin binding to actin in smooth muscle cells and skeletal muscle fibers through a series of interactions differing from the one described in section 8.10.) Smooth muscle relaxation results in dilation of the blood vessels, or vasodilation. The capacity of the vessels to dilate in response to increased blood flow, a property termed flow-mediated dilation, is considered an index of cardiovascular health.
As Green and coworkers review, training improves flow-mediated dilation—especially in individuals with or at risk of CVD—and reduces arterial wall stiffness by enhancing the endothelium-dependent signal transduction pathway described earlier. The enhancement includes higher eNOS content or activity. It is also possible that training influences other pathways of flow-mediated dilation. In addition, training increases the diameter of vessels—such as the coronary arteries, as well as arteries that nourish the exercising limbs—thus supplying more blood where it is needed. The stimulus, again, appears to be the increased shear stress imposed by blood on the endothelium with exercise.
Finally, training influences the smaller blood vessels: It increases the amount and diameter of the arterioles (the branches of arteries leading to capillaries) and muscle capillarization. The latter is measured as either the total number of capillaries in a muscle, or the number of capillaries per muscle fiber, or capillary density (defined in section 14.15 as the number of capillaries per unit of muscle cross-sectional area). Increased capillarization enhances the delivery of nutrients and O2 to muscle, as well as the uptake of muscle CO2 by blood.
Training-induced capillarization may be due to increased blood flow or to muscle activity itself. Both factors may promote the release of vascular endothelial growth factor (VEGF), a key angiogenic (that is, vessel-generating) protein, from muscle fibers. VEGF binds to the VEGF receptor in the plasma membrane of endothelial cells and activates a variety of signal transduction pathways, leading to endothelial cell proliferation and, hence, formation of new capillaries.
You can see that training provides more than one way of increasing blood supply to the active muscles. It seems that these beneficial adaptations can be elicited by endurance, resistance, and interval training. Improvements in vascular function with training are evident in both healthy humans and (possibly more evident) humans with or at risk of CVD.
Control of Muscle Activity by Ca2+
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered.
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered. Today we know that Ca2+ controls muscle activity and that it does so by permitting the binding of myosin to F-actin. This action of Ca2+ is not direct but indirect. As the Japanese physiologist Setsuro Ebashi discovered in the 1960s, control is exerted through tropomyosin and troponin, the two proteins that coexist with actin in the thin filaments, constituting about one third of the thin-filament mass. Let's meet them.
Tropomyosin has a molecular mass of 70 kDa and consists of two similar stringlike subunits in -helical conformation. The two subunits wind around each other just as the myosin heavy chains do in the myosin tail. The resulting extremely long tropomyosin molecules join in a row to form fibers. Two such fibers run along each thin filament while following the twisting of the actin monomers (figure 8.11).
Figure 8.11 Thin-filament proteins. A thin filament consists of an F-actin fiber (the double necklace of figure 8.7), two series of tropomyosin molecules, and troponin (Tn) complexes placed at regular intervals. Each troponin complex consists of TnC, which is the Ca2+ acceptor; TnI, which binds to actin; and TnT, which extends by way of a long tail along tropomyosin.
Adapted from L. Smillie and S. Ebashi, Essays in Biochemistry, vol. 10, edited by P.N. Campbell and F. Dickens (Orlando, FL: Academic, 1974), 1-35; C. Cohen Scientific America 233 (1975): 36 - 45. Courtesy of L. Smillie.
Troponin, symbolized as Tn, is a complex of three different subunits: TnC (18 kDa), TnI (24 kDa), and TnT (37 kDa). TnC binds Ca2+, TnI binds to actin, and TnT binds to tropomyosin. Two troponin complexes appear on the two sides of a thin filament every 39 nm, which is approximately the length of a tropomyosin molecule. One troponin complex attached to one tropomyosin molecule controls approximately seven actin monomers.
When a muscle is at rest (relaxed), the cytosol has a very low [Ca2+], approximately 10-7 mol · L-1. Researchers believe that, in this case, interactions among F-actin, TnI, TnT, and tropomyosin hold the latter close to the sites on the actin monomers where the myosin heads bind. Thus, tropomyosin hinders the interaction of thin and thick filaments. As we will see in the next section, muscle excitation by the nervous system results in the release of Ca2+ from an intracellular reservoir called the sarcoplasmic reticulum. This release causes a 100-fold surge in the cytosolic [Ca2+], from 10-7 to 10-5 mol · L-1.
The increased Ca2+ ions encounter TnC, bind to it, and elicit a change in its conformation. As a result, TnC detaches TnI from F-actin. This detachment lets tropomyosin move over the surface of the thin filament, away from the binding sites of myosin on F-actin. Myosin then binds to F-actin, and the muscle contracts. In fact, there is evidence that myosin binding to F-actin is cooperative; that is, the binding of some myosin heads facilitates the binding of additional ones by promoting the displacement of tropomyosin. This effect is reminiscent of the cooperative binding of O2 to hemoglobin (section 3.12).
Muscle activity continues until Ca2+ is sequestered in the sarcoplasmic reticulum (in a manner that we will examine shortly). The actin-TnI-TnT-tropomyosin interaction is then restored. Tropomyosin returns to a position hindering cross-bridge formation, and the muscle relaxes. The chain of events through which Ca2+ controls muscle contraction is summarized in figure 8.12.
Figure 8.12 Control of muscle contraction and relaxation by Ca2+. Ca2+ controls muscle contraction (left) and relaxation (right) through a series of protein interactions triggered by, respectively, Ca2+ release from and sequestration in the sarcoplasmic reticulum and involving troponin, tropomyosin, actin, and myosin.
What are triacylglycerols, and how do they serve us?
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils.
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils. Because of this abundance, they constitute 90% to 95% of dietary fat. In both animals and plants, triacylglycerols serve mainly as energy depots.
A triacylglycerol consists of a glycerol unit and three fatty acid units. Glycerol (figure 5.12), also known as glycerin or glycerine, is a compound of three carbons and three hydroxyl groups, each of which connects with the carboxyl group of a fatty acid to form an ester linkage. Thus, every triacylglycerol (figure 5.12) contains three ester linkages, which makes it a triester.
Figure 5.12 Glycerol and triacylglycerol. Triacylglycerols, the largest energy depot in living organisms, are triesters of glycerol and fatty acids. R1, R2, and R3 represent the aliphatic chains of the fatty acids, which usually differ. Acyl groups are shown in color.
Because there is a great variety of available fatty acids, and because any of them can be linked to any of the hydroxyl groups of glycerol, we end up with an even greater variety of triacylglycerols. Chances are that there will be both saturated and unsaturated fatty acids present in a single triacylglycerol. Therefore, it is not accurate to state that a certain food contains only saturated or unsaturated fat. Instead, one should state that a certain food contains primarily saturated or unsaturated fatty acids.
Triacylglycerols are hydrophobic, which is evident by the immiscibility of fats or oils with water. Moreover, triacylglycerols have low thermal conductivity, rendering the subcutaneous fat of animals an efficient insulator of their internal organs against cold exposure.
The part of a fatty acid connected to an oxygen of glycerol in a triacylglycerol is called an acyl group. This is where the term tri-acyl-glycerol comes from; hence it is more accurate than triglyceride. The acyl groups derive from the ion of a fatty acid by removal of O-, and they bear the name of the fatty acid with the ending -oyl in place of -ate. Thus, the acyl group of palmitate is called the palmitoyl group.
The difference in melting point between saturated and unsaturated fatty acids described in the previous section is reflected in triacylglycerols: The more saturated acyl groups they contain, the higher their melting point is. Triacylglycerols of animal origin have a high content of saturated acyl groups, which is why animal fat is solid at room temperature. Conversely, plant triacylglycerols have a high content of unsaturated acyl groups, which is why vegetable oils are liquid in the same conditions.
Adaptations of the Vasculature to Training
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol.
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol. On top of these effects, endurance training contributes to lowering the risk of atherosclerosis by increasing HDL cholesterol.
In addition, the increases in blood flow and pressure accompanying exercise cause structural and functional adaptations of the vascular wall that lower the risk of atherosclerosis. These beneficial effects seem to be mediated by the endothelium, the single layer of cells lining the interior surface of the blood vessels, in direct contact with blood on the inside and surrounded by smooth muscle cells on the outside (figure 15.3).
Figure 15.3 How exercise elicits vasodilation. The increase in the pumping activity of the heart during exercise augments the shear stress on the endothelial cells lining the blood vessels. This mechanical stimulus leads to activation of eNOS, which catalyzes the synthesis of NO from arginine. NO diffuses to the smooth muscle cells forming the walls of blood vessels and activates soluble guanylate cyclase, which catalyzes the synthesis of cyclic GMP (cGMP) from GTP. Cyclic GMP activates PKG, leading to a drop in the cytosolic Ca2+ concentration, relaxation of the smooth muscle cells, and vasodilation.
The endothelial cells possess a variety of proteins that convert the mechanical stimulus of the exercise-induced increase in shear stress into chemical signals. In turn, these signals activate endothelial nitrogen oxide synthase (eNOS). This enzyme catalyzes the synthesis of nitric oxide (introduced in section 1.5) from arginine and oxygen in a reaction requiring NADPH as a reductant and yielding citrulline (the intermediate compound of the urea cycle introduced in section 12.9 and figure 12.10) in addition to NO.
NO diffuses out of the endothelial cells and enters neighboring smooth muscle cells, where it activates soluble guanylate cyclase, a cytosolic enzyme that catalyzes the formation of cyclic guanylate, or cyclic GMP (cGMP), from GTP, in a manner analogous to the synthesis of cAMP (section 10.6 and reaction 10.5).
Cyclic GMP, in turn, activates cGMP-dependent protein kinase, or PKG, which promotes smooth muscle relaxation by activating an ion pump that removes Ca2+ from the cytosol, thus preventing the interaction of myosin and actin. (Ca2+ allows myosin binding to actin in smooth muscle cells and skeletal muscle fibers through a series of interactions differing from the one described in section 8.10.) Smooth muscle relaxation results in dilation of the blood vessels, or vasodilation. The capacity of the vessels to dilate in response to increased blood flow, a property termed flow-mediated dilation, is considered an index of cardiovascular health.
As Green and coworkers review, training improves flow-mediated dilation—especially in individuals with or at risk of CVD—and reduces arterial wall stiffness by enhancing the endothelium-dependent signal transduction pathway described earlier. The enhancement includes higher eNOS content or activity. It is also possible that training influences other pathways of flow-mediated dilation. In addition, training increases the diameter of vessels—such as the coronary arteries, as well as arteries that nourish the exercising limbs—thus supplying more blood where it is needed. The stimulus, again, appears to be the increased shear stress imposed by blood on the endothelium with exercise.
Finally, training influences the smaller blood vessels: It increases the amount and diameter of the arterioles (the branches of arteries leading to capillaries) and muscle capillarization. The latter is measured as either the total number of capillaries in a muscle, or the number of capillaries per muscle fiber, or capillary density (defined in section 14.15 as the number of capillaries per unit of muscle cross-sectional area). Increased capillarization enhances the delivery of nutrients and O2 to muscle, as well as the uptake of muscle CO2 by blood.
Training-induced capillarization may be due to increased blood flow or to muscle activity itself. Both factors may promote the release of vascular endothelial growth factor (VEGF), a key angiogenic (that is, vessel-generating) protein, from muscle fibers. VEGF binds to the VEGF receptor in the plasma membrane of endothelial cells and activates a variety of signal transduction pathways, leading to endothelial cell proliferation and, hence, formation of new capillaries.
You can see that training provides more than one way of increasing blood supply to the active muscles. It seems that these beneficial adaptations can be elicited by endurance, resistance, and interval training. Improvements in vascular function with training are evident in both healthy humans and (possibly more evident) humans with or at risk of CVD.
Control of Muscle Activity by Ca2+
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered.
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered. Today we know that Ca2+ controls muscle activity and that it does so by permitting the binding of myosin to F-actin. This action of Ca2+ is not direct but indirect. As the Japanese physiologist Setsuro Ebashi discovered in the 1960s, control is exerted through tropomyosin and troponin, the two proteins that coexist with actin in the thin filaments, constituting about one third of the thin-filament mass. Let's meet them.
Tropomyosin has a molecular mass of 70 kDa and consists of two similar stringlike subunits in -helical conformation. The two subunits wind around each other just as the myosin heavy chains do in the myosin tail. The resulting extremely long tropomyosin molecules join in a row to form fibers. Two such fibers run along each thin filament while following the twisting of the actin monomers (figure 8.11).
Figure 8.11 Thin-filament proteins. A thin filament consists of an F-actin fiber (the double necklace of figure 8.7), two series of tropomyosin molecules, and troponin (Tn) complexes placed at regular intervals. Each troponin complex consists of TnC, which is the Ca2+ acceptor; TnI, which binds to actin; and TnT, which extends by way of a long tail along tropomyosin.
Adapted from L. Smillie and S. Ebashi, Essays in Biochemistry, vol. 10, edited by P.N. Campbell and F. Dickens (Orlando, FL: Academic, 1974), 1-35; C. Cohen Scientific America 233 (1975): 36 - 45. Courtesy of L. Smillie.
Troponin, symbolized as Tn, is a complex of three different subunits: TnC (18 kDa), TnI (24 kDa), and TnT (37 kDa). TnC binds Ca2+, TnI binds to actin, and TnT binds to tropomyosin. Two troponin complexes appear on the two sides of a thin filament every 39 nm, which is approximately the length of a tropomyosin molecule. One troponin complex attached to one tropomyosin molecule controls approximately seven actin monomers.
When a muscle is at rest (relaxed), the cytosol has a very low [Ca2+], approximately 10-7 mol · L-1. Researchers believe that, in this case, interactions among F-actin, TnI, TnT, and tropomyosin hold the latter close to the sites on the actin monomers where the myosin heads bind. Thus, tropomyosin hinders the interaction of thin and thick filaments. As we will see in the next section, muscle excitation by the nervous system results in the release of Ca2+ from an intracellular reservoir called the sarcoplasmic reticulum. This release causes a 100-fold surge in the cytosolic [Ca2+], from 10-7 to 10-5 mol · L-1.
The increased Ca2+ ions encounter TnC, bind to it, and elicit a change in its conformation. As a result, TnC detaches TnI from F-actin. This detachment lets tropomyosin move over the surface of the thin filament, away from the binding sites of myosin on F-actin. Myosin then binds to F-actin, and the muscle contracts. In fact, there is evidence that myosin binding to F-actin is cooperative; that is, the binding of some myosin heads facilitates the binding of additional ones by promoting the displacement of tropomyosin. This effect is reminiscent of the cooperative binding of O2 to hemoglobin (section 3.12).
Muscle activity continues until Ca2+ is sequestered in the sarcoplasmic reticulum (in a manner that we will examine shortly). The actin-TnI-TnT-tropomyosin interaction is then restored. Tropomyosin returns to a position hindering cross-bridge formation, and the muscle relaxes. The chain of events through which Ca2+ controls muscle contraction is summarized in figure 8.12.
Figure 8.12 Control of muscle contraction and relaxation by Ca2+. Ca2+ controls muscle contraction (left) and relaxation (right) through a series of protein interactions triggered by, respectively, Ca2+ release from and sequestration in the sarcoplasmic reticulum and involving troponin, tropomyosin, actin, and myosin.
What are triacylglycerols, and how do they serve us?
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils.
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils. Because of this abundance, they constitute 90% to 95% of dietary fat. In both animals and plants, triacylglycerols serve mainly as energy depots.
A triacylglycerol consists of a glycerol unit and three fatty acid units. Glycerol (figure 5.12), also known as glycerin or glycerine, is a compound of three carbons and three hydroxyl groups, each of which connects with the carboxyl group of a fatty acid to form an ester linkage. Thus, every triacylglycerol (figure 5.12) contains three ester linkages, which makes it a triester.
Figure 5.12 Glycerol and triacylglycerol. Triacylglycerols, the largest energy depot in living organisms, are triesters of glycerol and fatty acids. R1, R2, and R3 represent the aliphatic chains of the fatty acids, which usually differ. Acyl groups are shown in color.
Because there is a great variety of available fatty acids, and because any of them can be linked to any of the hydroxyl groups of glycerol, we end up with an even greater variety of triacylglycerols. Chances are that there will be both saturated and unsaturated fatty acids present in a single triacylglycerol. Therefore, it is not accurate to state that a certain food contains only saturated or unsaturated fat. Instead, one should state that a certain food contains primarily saturated or unsaturated fatty acids.
Triacylglycerols are hydrophobic, which is evident by the immiscibility of fats or oils with water. Moreover, triacylglycerols have low thermal conductivity, rendering the subcutaneous fat of animals an efficient insulator of their internal organs against cold exposure.
The part of a fatty acid connected to an oxygen of glycerol in a triacylglycerol is called an acyl group. This is where the term tri-acyl-glycerol comes from; hence it is more accurate than triglyceride. The acyl groups derive from the ion of a fatty acid by removal of O-, and they bear the name of the fatty acid with the ending -oyl in place of -ate. Thus, the acyl group of palmitate is called the palmitoyl group.
The difference in melting point between saturated and unsaturated fatty acids described in the previous section is reflected in triacylglycerols: The more saturated acyl groups they contain, the higher their melting point is. Triacylglycerols of animal origin have a high content of saturated acyl groups, which is why animal fat is solid at room temperature. Conversely, plant triacylglycerols have a high content of unsaturated acyl groups, which is why vegetable oils are liquid in the same conditions.
Adaptations of the Vasculature to Training
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol.
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol. On top of these effects, endurance training contributes to lowering the risk of atherosclerosis by increasing HDL cholesterol.
In addition, the increases in blood flow and pressure accompanying exercise cause structural and functional adaptations of the vascular wall that lower the risk of atherosclerosis. These beneficial effects seem to be mediated by the endothelium, the single layer of cells lining the interior surface of the blood vessels, in direct contact with blood on the inside and surrounded by smooth muscle cells on the outside (figure 15.3).
Figure 15.3 How exercise elicits vasodilation. The increase in the pumping activity of the heart during exercise augments the shear stress on the endothelial cells lining the blood vessels. This mechanical stimulus leads to activation of eNOS, which catalyzes the synthesis of NO from arginine. NO diffuses to the smooth muscle cells forming the walls of blood vessels and activates soluble guanylate cyclase, which catalyzes the synthesis of cyclic GMP (cGMP) from GTP. Cyclic GMP activates PKG, leading to a drop in the cytosolic Ca2+ concentration, relaxation of the smooth muscle cells, and vasodilation.
The endothelial cells possess a variety of proteins that convert the mechanical stimulus of the exercise-induced increase in shear stress into chemical signals. In turn, these signals activate endothelial nitrogen oxide synthase (eNOS). This enzyme catalyzes the synthesis of nitric oxide (introduced in section 1.5) from arginine and oxygen in a reaction requiring NADPH as a reductant and yielding citrulline (the intermediate compound of the urea cycle introduced in section 12.9 and figure 12.10) in addition to NO.
NO diffuses out of the endothelial cells and enters neighboring smooth muscle cells, where it activates soluble guanylate cyclase, a cytosolic enzyme that catalyzes the formation of cyclic guanylate, or cyclic GMP (cGMP), from GTP, in a manner analogous to the synthesis of cAMP (section 10.6 and reaction 10.5).
Cyclic GMP, in turn, activates cGMP-dependent protein kinase, or PKG, which promotes smooth muscle relaxation by activating an ion pump that removes Ca2+ from the cytosol, thus preventing the interaction of myosin and actin. (Ca2+ allows myosin binding to actin in smooth muscle cells and skeletal muscle fibers through a series of interactions differing from the one described in section 8.10.) Smooth muscle relaxation results in dilation of the blood vessels, or vasodilation. The capacity of the vessels to dilate in response to increased blood flow, a property termed flow-mediated dilation, is considered an index of cardiovascular health.
As Green and coworkers review, training improves flow-mediated dilation—especially in individuals with or at risk of CVD—and reduces arterial wall stiffness by enhancing the endothelium-dependent signal transduction pathway described earlier. The enhancement includes higher eNOS content or activity. It is also possible that training influences other pathways of flow-mediated dilation. In addition, training increases the diameter of vessels—such as the coronary arteries, as well as arteries that nourish the exercising limbs—thus supplying more blood where it is needed. The stimulus, again, appears to be the increased shear stress imposed by blood on the endothelium with exercise.
Finally, training influences the smaller blood vessels: It increases the amount and diameter of the arterioles (the branches of arteries leading to capillaries) and muscle capillarization. The latter is measured as either the total number of capillaries in a muscle, or the number of capillaries per muscle fiber, or capillary density (defined in section 14.15 as the number of capillaries per unit of muscle cross-sectional area). Increased capillarization enhances the delivery of nutrients and O2 to muscle, as well as the uptake of muscle CO2 by blood.
Training-induced capillarization may be due to increased blood flow or to muscle activity itself. Both factors may promote the release of vascular endothelial growth factor (VEGF), a key angiogenic (that is, vessel-generating) protein, from muscle fibers. VEGF binds to the VEGF receptor in the plasma membrane of endothelial cells and activates a variety of signal transduction pathways, leading to endothelial cell proliferation and, hence, formation of new capillaries.
You can see that training provides more than one way of increasing blood supply to the active muscles. It seems that these beneficial adaptations can be elicited by endurance, resistance, and interval training. Improvements in vascular function with training are evident in both healthy humans and (possibly more evident) humans with or at risk of CVD.
Control of Muscle Activity by Ca2+
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered.
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered. Today we know that Ca2+ controls muscle activity and that it does so by permitting the binding of myosin to F-actin. This action of Ca2+ is not direct but indirect. As the Japanese physiologist Setsuro Ebashi discovered in the 1960s, control is exerted through tropomyosin and troponin, the two proteins that coexist with actin in the thin filaments, constituting about one third of the thin-filament mass. Let's meet them.
Tropomyosin has a molecular mass of 70 kDa and consists of two similar stringlike subunits in -helical conformation. The two subunits wind around each other just as the myosin heavy chains do in the myosin tail. The resulting extremely long tropomyosin molecules join in a row to form fibers. Two such fibers run along each thin filament while following the twisting of the actin monomers (figure 8.11).
Figure 8.11 Thin-filament proteins. A thin filament consists of an F-actin fiber (the double necklace of figure 8.7), two series of tropomyosin molecules, and troponin (Tn) complexes placed at regular intervals. Each troponin complex consists of TnC, which is the Ca2+ acceptor; TnI, which binds to actin; and TnT, which extends by way of a long tail along tropomyosin.
Adapted from L. Smillie and S. Ebashi, Essays in Biochemistry, vol. 10, edited by P.N. Campbell and F. Dickens (Orlando, FL: Academic, 1974), 1-35; C. Cohen Scientific America 233 (1975): 36 - 45. Courtesy of L. Smillie.
Troponin, symbolized as Tn, is a complex of three different subunits: TnC (18 kDa), TnI (24 kDa), and TnT (37 kDa). TnC binds Ca2+, TnI binds to actin, and TnT binds to tropomyosin. Two troponin complexes appear on the two sides of a thin filament every 39 nm, which is approximately the length of a tropomyosin molecule. One troponin complex attached to one tropomyosin molecule controls approximately seven actin monomers.
When a muscle is at rest (relaxed), the cytosol has a very low [Ca2+], approximately 10-7 mol · L-1. Researchers believe that, in this case, interactions among F-actin, TnI, TnT, and tropomyosin hold the latter close to the sites on the actin monomers where the myosin heads bind. Thus, tropomyosin hinders the interaction of thin and thick filaments. As we will see in the next section, muscle excitation by the nervous system results in the release of Ca2+ from an intracellular reservoir called the sarcoplasmic reticulum. This release causes a 100-fold surge in the cytosolic [Ca2+], from 10-7 to 10-5 mol · L-1.
The increased Ca2+ ions encounter TnC, bind to it, and elicit a change in its conformation. As a result, TnC detaches TnI from F-actin. This detachment lets tropomyosin move over the surface of the thin filament, away from the binding sites of myosin on F-actin. Myosin then binds to F-actin, and the muscle contracts. In fact, there is evidence that myosin binding to F-actin is cooperative; that is, the binding of some myosin heads facilitates the binding of additional ones by promoting the displacement of tropomyosin. This effect is reminiscent of the cooperative binding of O2 to hemoglobin (section 3.12).
Muscle activity continues until Ca2+ is sequestered in the sarcoplasmic reticulum (in a manner that we will examine shortly). The actin-TnI-TnT-tropomyosin interaction is then restored. Tropomyosin returns to a position hindering cross-bridge formation, and the muscle relaxes. The chain of events through which Ca2+ controls muscle contraction is summarized in figure 8.12.
Figure 8.12 Control of muscle contraction and relaxation by Ca2+. Ca2+ controls muscle contraction (left) and relaxation (right) through a series of protein interactions triggered by, respectively, Ca2+ release from and sequestration in the sarcoplasmic reticulum and involving troponin, tropomyosin, actin, and myosin.
What are triacylglycerols, and how do they serve us?
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils.
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils. Because of this abundance, they constitute 90% to 95% of dietary fat. In both animals and plants, triacylglycerols serve mainly as energy depots.
A triacylglycerol consists of a glycerol unit and three fatty acid units. Glycerol (figure 5.12), also known as glycerin or glycerine, is a compound of three carbons and three hydroxyl groups, each of which connects with the carboxyl group of a fatty acid to form an ester linkage. Thus, every triacylglycerol (figure 5.12) contains three ester linkages, which makes it a triester.
Figure 5.12 Glycerol and triacylglycerol. Triacylglycerols, the largest energy depot in living organisms, are triesters of glycerol and fatty acids. R1, R2, and R3 represent the aliphatic chains of the fatty acids, which usually differ. Acyl groups are shown in color.
Because there is a great variety of available fatty acids, and because any of them can be linked to any of the hydroxyl groups of glycerol, we end up with an even greater variety of triacylglycerols. Chances are that there will be both saturated and unsaturated fatty acids present in a single triacylglycerol. Therefore, it is not accurate to state that a certain food contains only saturated or unsaturated fat. Instead, one should state that a certain food contains primarily saturated or unsaturated fatty acids.
Triacylglycerols are hydrophobic, which is evident by the immiscibility of fats or oils with water. Moreover, triacylglycerols have low thermal conductivity, rendering the subcutaneous fat of animals an efficient insulator of their internal organs against cold exposure.
The part of a fatty acid connected to an oxygen of glycerol in a triacylglycerol is called an acyl group. This is where the term tri-acyl-glycerol comes from; hence it is more accurate than triglyceride. The acyl groups derive from the ion of a fatty acid by removal of O-, and they bear the name of the fatty acid with the ending -oyl in place of -ate. Thus, the acyl group of palmitate is called the palmitoyl group.
The difference in melting point between saturated and unsaturated fatty acids described in the previous section is reflected in triacylglycerols: The more saturated acyl groups they contain, the higher their melting point is. Triacylglycerols of animal origin have a high content of saturated acyl groups, which is why animal fat is solid at room temperature. Conversely, plant triacylglycerols have a high content of unsaturated acyl groups, which is why vegetable oils are liquid in the same conditions.
Adaptations of the Vasculature to Training
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol.
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol. On top of these effects, endurance training contributes to lowering the risk of atherosclerosis by increasing HDL cholesterol.
In addition, the increases in blood flow and pressure accompanying exercise cause structural and functional adaptations of the vascular wall that lower the risk of atherosclerosis. These beneficial effects seem to be mediated by the endothelium, the single layer of cells lining the interior surface of the blood vessels, in direct contact with blood on the inside and surrounded by smooth muscle cells on the outside (figure 15.3).
Figure 15.3 How exercise elicits vasodilation. The increase in the pumping activity of the heart during exercise augments the shear stress on the endothelial cells lining the blood vessels. This mechanical stimulus leads to activation of eNOS, which catalyzes the synthesis of NO from arginine. NO diffuses to the smooth muscle cells forming the walls of blood vessels and activates soluble guanylate cyclase, which catalyzes the synthesis of cyclic GMP (cGMP) from GTP. Cyclic GMP activates PKG, leading to a drop in the cytosolic Ca2+ concentration, relaxation of the smooth muscle cells, and vasodilation.
The endothelial cells possess a variety of proteins that convert the mechanical stimulus of the exercise-induced increase in shear stress into chemical signals. In turn, these signals activate endothelial nitrogen oxide synthase (eNOS). This enzyme catalyzes the synthesis of nitric oxide (introduced in section 1.5) from arginine and oxygen in a reaction requiring NADPH as a reductant and yielding citrulline (the intermediate compound of the urea cycle introduced in section 12.9 and figure 12.10) in addition to NO.
NO diffuses out of the endothelial cells and enters neighboring smooth muscle cells, where it activates soluble guanylate cyclase, a cytosolic enzyme that catalyzes the formation of cyclic guanylate, or cyclic GMP (cGMP), from GTP, in a manner analogous to the synthesis of cAMP (section 10.6 and reaction 10.5).
Cyclic GMP, in turn, activates cGMP-dependent protein kinase, or PKG, which promotes smooth muscle relaxation by activating an ion pump that removes Ca2+ from the cytosol, thus preventing the interaction of myosin and actin. (Ca2+ allows myosin binding to actin in smooth muscle cells and skeletal muscle fibers through a series of interactions differing from the one described in section 8.10.) Smooth muscle relaxation results in dilation of the blood vessels, or vasodilation. The capacity of the vessels to dilate in response to increased blood flow, a property termed flow-mediated dilation, is considered an index of cardiovascular health.
As Green and coworkers review, training improves flow-mediated dilation—especially in individuals with or at risk of CVD—and reduces arterial wall stiffness by enhancing the endothelium-dependent signal transduction pathway described earlier. The enhancement includes higher eNOS content or activity. It is also possible that training influences other pathways of flow-mediated dilation. In addition, training increases the diameter of vessels—such as the coronary arteries, as well as arteries that nourish the exercising limbs—thus supplying more blood where it is needed. The stimulus, again, appears to be the increased shear stress imposed by blood on the endothelium with exercise.
Finally, training influences the smaller blood vessels: It increases the amount and diameter of the arterioles (the branches of arteries leading to capillaries) and muscle capillarization. The latter is measured as either the total number of capillaries in a muscle, or the number of capillaries per muscle fiber, or capillary density (defined in section 14.15 as the number of capillaries per unit of muscle cross-sectional area). Increased capillarization enhances the delivery of nutrients and O2 to muscle, as well as the uptake of muscle CO2 by blood.
Training-induced capillarization may be due to increased blood flow or to muscle activity itself. Both factors may promote the release of vascular endothelial growth factor (VEGF), a key angiogenic (that is, vessel-generating) protein, from muscle fibers. VEGF binds to the VEGF receptor in the plasma membrane of endothelial cells and activates a variety of signal transduction pathways, leading to endothelial cell proliferation and, hence, formation of new capillaries.
You can see that training provides more than one way of increasing blood supply to the active muscles. It seems that these beneficial adaptations can be elicited by endurance, resistance, and interval training. Improvements in vascular function with training are evident in both healthy humans and (possibly more evident) humans with or at risk of CVD.
Control of Muscle Activity by Ca2+
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered.
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered. Today we know that Ca2+ controls muscle activity and that it does so by permitting the binding of myosin to F-actin. This action of Ca2+ is not direct but indirect. As the Japanese physiologist Setsuro Ebashi discovered in the 1960s, control is exerted through tropomyosin and troponin, the two proteins that coexist with actin in the thin filaments, constituting about one third of the thin-filament mass. Let's meet them.
Tropomyosin has a molecular mass of 70 kDa and consists of two similar stringlike subunits in -helical conformation. The two subunits wind around each other just as the myosin heavy chains do in the myosin tail. The resulting extremely long tropomyosin molecules join in a row to form fibers. Two such fibers run along each thin filament while following the twisting of the actin monomers (figure 8.11).
Figure 8.11 Thin-filament proteins. A thin filament consists of an F-actin fiber (the double necklace of figure 8.7), two series of tropomyosin molecules, and troponin (Tn) complexes placed at regular intervals. Each troponin complex consists of TnC, which is the Ca2+ acceptor; TnI, which binds to actin; and TnT, which extends by way of a long tail along tropomyosin.
Adapted from L. Smillie and S. Ebashi, Essays in Biochemistry, vol. 10, edited by P.N. Campbell and F. Dickens (Orlando, FL: Academic, 1974), 1-35; C. Cohen Scientific America 233 (1975): 36 - 45. Courtesy of L. Smillie.
Troponin, symbolized as Tn, is a complex of three different subunits: TnC (18 kDa), TnI (24 kDa), and TnT (37 kDa). TnC binds Ca2+, TnI binds to actin, and TnT binds to tropomyosin. Two troponin complexes appear on the two sides of a thin filament every 39 nm, which is approximately the length of a tropomyosin molecule. One troponin complex attached to one tropomyosin molecule controls approximately seven actin monomers.
When a muscle is at rest (relaxed), the cytosol has a very low [Ca2+], approximately 10-7 mol · L-1. Researchers believe that, in this case, interactions among F-actin, TnI, TnT, and tropomyosin hold the latter close to the sites on the actin monomers where the myosin heads bind. Thus, tropomyosin hinders the interaction of thin and thick filaments. As we will see in the next section, muscle excitation by the nervous system results in the release of Ca2+ from an intracellular reservoir called the sarcoplasmic reticulum. This release causes a 100-fold surge in the cytosolic [Ca2+], from 10-7 to 10-5 mol · L-1.
The increased Ca2+ ions encounter TnC, bind to it, and elicit a change in its conformation. As a result, TnC detaches TnI from F-actin. This detachment lets tropomyosin move over the surface of the thin filament, away from the binding sites of myosin on F-actin. Myosin then binds to F-actin, and the muscle contracts. In fact, there is evidence that myosin binding to F-actin is cooperative; that is, the binding of some myosin heads facilitates the binding of additional ones by promoting the displacement of tropomyosin. This effect is reminiscent of the cooperative binding of O2 to hemoglobin (section 3.12).
Muscle activity continues until Ca2+ is sequestered in the sarcoplasmic reticulum (in a manner that we will examine shortly). The actin-TnI-TnT-tropomyosin interaction is then restored. Tropomyosin returns to a position hindering cross-bridge formation, and the muscle relaxes. The chain of events through which Ca2+ controls muscle contraction is summarized in figure 8.12.
Figure 8.12 Control of muscle contraction and relaxation by Ca2+. Ca2+ controls muscle contraction (left) and relaxation (right) through a series of protein interactions triggered by, respectively, Ca2+ release from and sequestration in the sarcoplasmic reticulum and involving troponin, tropomyosin, actin, and myosin.
What are triacylglycerols, and how do they serve us?
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils.
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils. Because of this abundance, they constitute 90% to 95% of dietary fat. In both animals and plants, triacylglycerols serve mainly as energy depots.
A triacylglycerol consists of a glycerol unit and three fatty acid units. Glycerol (figure 5.12), also known as glycerin or glycerine, is a compound of three carbons and three hydroxyl groups, each of which connects with the carboxyl group of a fatty acid to form an ester linkage. Thus, every triacylglycerol (figure 5.12) contains three ester linkages, which makes it a triester.
Figure 5.12 Glycerol and triacylglycerol. Triacylglycerols, the largest energy depot in living organisms, are triesters of glycerol and fatty acids. R1, R2, and R3 represent the aliphatic chains of the fatty acids, which usually differ. Acyl groups are shown in color.
Because there is a great variety of available fatty acids, and because any of them can be linked to any of the hydroxyl groups of glycerol, we end up with an even greater variety of triacylglycerols. Chances are that there will be both saturated and unsaturated fatty acids present in a single triacylglycerol. Therefore, it is not accurate to state that a certain food contains only saturated or unsaturated fat. Instead, one should state that a certain food contains primarily saturated or unsaturated fatty acids.
Triacylglycerols are hydrophobic, which is evident by the immiscibility of fats or oils with water. Moreover, triacylglycerols have low thermal conductivity, rendering the subcutaneous fat of animals an efficient insulator of their internal organs against cold exposure.
The part of a fatty acid connected to an oxygen of glycerol in a triacylglycerol is called an acyl group. This is where the term tri-acyl-glycerol comes from; hence it is more accurate than triglyceride. The acyl groups derive from the ion of a fatty acid by removal of O-, and they bear the name of the fatty acid with the ending -oyl in place of -ate. Thus, the acyl group of palmitate is called the palmitoyl group.
The difference in melting point between saturated and unsaturated fatty acids described in the previous section is reflected in triacylglycerols: The more saturated acyl groups they contain, the higher their melting point is. Triacylglycerols of animal origin have a high content of saturated acyl groups, which is why animal fat is solid at room temperature. Conversely, plant triacylglycerols have a high content of unsaturated acyl groups, which is why vegetable oils are liquid in the same conditions.
Adaptations of the Vasculature to Training
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol.
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol. On top of these effects, endurance training contributes to lowering the risk of atherosclerosis by increasing HDL cholesterol.
In addition, the increases in blood flow and pressure accompanying exercise cause structural and functional adaptations of the vascular wall that lower the risk of atherosclerosis. These beneficial effects seem to be mediated by the endothelium, the single layer of cells lining the interior surface of the blood vessels, in direct contact with blood on the inside and surrounded by smooth muscle cells on the outside (figure 15.3).
Figure 15.3 How exercise elicits vasodilation. The increase in the pumping activity of the heart during exercise augments the shear stress on the endothelial cells lining the blood vessels. This mechanical stimulus leads to activation of eNOS, which catalyzes the synthesis of NO from arginine. NO diffuses to the smooth muscle cells forming the walls of blood vessels and activates soluble guanylate cyclase, which catalyzes the synthesis of cyclic GMP (cGMP) from GTP. Cyclic GMP activates PKG, leading to a drop in the cytosolic Ca2+ concentration, relaxation of the smooth muscle cells, and vasodilation.
The endothelial cells possess a variety of proteins that convert the mechanical stimulus of the exercise-induced increase in shear stress into chemical signals. In turn, these signals activate endothelial nitrogen oxide synthase (eNOS). This enzyme catalyzes the synthesis of nitric oxide (introduced in section 1.5) from arginine and oxygen in a reaction requiring NADPH as a reductant and yielding citrulline (the intermediate compound of the urea cycle introduced in section 12.9 and figure 12.10) in addition to NO.
NO diffuses out of the endothelial cells and enters neighboring smooth muscle cells, where it activates soluble guanylate cyclase, a cytosolic enzyme that catalyzes the formation of cyclic guanylate, or cyclic GMP (cGMP), from GTP, in a manner analogous to the synthesis of cAMP (section 10.6 and reaction 10.5).
Cyclic GMP, in turn, activates cGMP-dependent protein kinase, or PKG, which promotes smooth muscle relaxation by activating an ion pump that removes Ca2+ from the cytosol, thus preventing the interaction of myosin and actin. (Ca2+ allows myosin binding to actin in smooth muscle cells and skeletal muscle fibers through a series of interactions differing from the one described in section 8.10.) Smooth muscle relaxation results in dilation of the blood vessels, or vasodilation. The capacity of the vessels to dilate in response to increased blood flow, a property termed flow-mediated dilation, is considered an index of cardiovascular health.
As Green and coworkers review, training improves flow-mediated dilation—especially in individuals with or at risk of CVD—and reduces arterial wall stiffness by enhancing the endothelium-dependent signal transduction pathway described earlier. The enhancement includes higher eNOS content or activity. It is also possible that training influences other pathways of flow-mediated dilation. In addition, training increases the diameter of vessels—such as the coronary arteries, as well as arteries that nourish the exercising limbs—thus supplying more blood where it is needed. The stimulus, again, appears to be the increased shear stress imposed by blood on the endothelium with exercise.
Finally, training influences the smaller blood vessels: It increases the amount and diameter of the arterioles (the branches of arteries leading to capillaries) and muscle capillarization. The latter is measured as either the total number of capillaries in a muscle, or the number of capillaries per muscle fiber, or capillary density (defined in section 14.15 as the number of capillaries per unit of muscle cross-sectional area). Increased capillarization enhances the delivery of nutrients and O2 to muscle, as well as the uptake of muscle CO2 by blood.
Training-induced capillarization may be due to increased blood flow or to muscle activity itself. Both factors may promote the release of vascular endothelial growth factor (VEGF), a key angiogenic (that is, vessel-generating) protein, from muscle fibers. VEGF binds to the VEGF receptor in the plasma membrane of endothelial cells and activates a variety of signal transduction pathways, leading to endothelial cell proliferation and, hence, formation of new capillaries.
You can see that training provides more than one way of increasing blood supply to the active muscles. It seems that these beneficial adaptations can be elicited by endurance, resistance, and interval training. Improvements in vascular function with training are evident in both healthy humans and (possibly more evident) humans with or at risk of CVD.
Control of Muscle Activity by Ca2+
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered.
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered. Today we know that Ca2+ controls muscle activity and that it does so by permitting the binding of myosin to F-actin. This action of Ca2+ is not direct but indirect. As the Japanese physiologist Setsuro Ebashi discovered in the 1960s, control is exerted through tropomyosin and troponin, the two proteins that coexist with actin in the thin filaments, constituting about one third of the thin-filament mass. Let's meet them.
Tropomyosin has a molecular mass of 70 kDa and consists of two similar stringlike subunits in -helical conformation. The two subunits wind around each other just as the myosin heavy chains do in the myosin tail. The resulting extremely long tropomyosin molecules join in a row to form fibers. Two such fibers run along each thin filament while following the twisting of the actin monomers (figure 8.11).
Figure 8.11 Thin-filament proteins. A thin filament consists of an F-actin fiber (the double necklace of figure 8.7), two series of tropomyosin molecules, and troponin (Tn) complexes placed at regular intervals. Each troponin complex consists of TnC, which is the Ca2+ acceptor; TnI, which binds to actin; and TnT, which extends by way of a long tail along tropomyosin.
Adapted from L. Smillie and S. Ebashi, Essays in Biochemistry, vol. 10, edited by P.N. Campbell and F. Dickens (Orlando, FL: Academic, 1974), 1-35; C. Cohen Scientific America 233 (1975): 36 - 45. Courtesy of L. Smillie.
Troponin, symbolized as Tn, is a complex of three different subunits: TnC (18 kDa), TnI (24 kDa), and TnT (37 kDa). TnC binds Ca2+, TnI binds to actin, and TnT binds to tropomyosin. Two troponin complexes appear on the two sides of a thin filament every 39 nm, which is approximately the length of a tropomyosin molecule. One troponin complex attached to one tropomyosin molecule controls approximately seven actin monomers.
When a muscle is at rest (relaxed), the cytosol has a very low [Ca2+], approximately 10-7 mol · L-1. Researchers believe that, in this case, interactions among F-actin, TnI, TnT, and tropomyosin hold the latter close to the sites on the actin monomers where the myosin heads bind. Thus, tropomyosin hinders the interaction of thin and thick filaments. As we will see in the next section, muscle excitation by the nervous system results in the release of Ca2+ from an intracellular reservoir called the sarcoplasmic reticulum. This release causes a 100-fold surge in the cytosolic [Ca2+], from 10-7 to 10-5 mol · L-1.
The increased Ca2+ ions encounter TnC, bind to it, and elicit a change in its conformation. As a result, TnC detaches TnI from F-actin. This detachment lets tropomyosin move over the surface of the thin filament, away from the binding sites of myosin on F-actin. Myosin then binds to F-actin, and the muscle contracts. In fact, there is evidence that myosin binding to F-actin is cooperative; that is, the binding of some myosin heads facilitates the binding of additional ones by promoting the displacement of tropomyosin. This effect is reminiscent of the cooperative binding of O2 to hemoglobin (section 3.12).
Muscle activity continues until Ca2+ is sequestered in the sarcoplasmic reticulum (in a manner that we will examine shortly). The actin-TnI-TnT-tropomyosin interaction is then restored. Tropomyosin returns to a position hindering cross-bridge formation, and the muscle relaxes. The chain of events through which Ca2+ controls muscle contraction is summarized in figure 8.12.
Figure 8.12 Control of muscle contraction and relaxation by Ca2+. Ca2+ controls muscle contraction (left) and relaxation (right) through a series of protein interactions triggered by, respectively, Ca2+ release from and sequestration in the sarcoplasmic reticulum and involving troponin, tropomyosin, actin, and myosin.
What are triacylglycerols, and how do they serve us?
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils.
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils. Because of this abundance, they constitute 90% to 95% of dietary fat. In both animals and plants, triacylglycerols serve mainly as energy depots.
A triacylglycerol consists of a glycerol unit and three fatty acid units. Glycerol (figure 5.12), also known as glycerin or glycerine, is a compound of three carbons and three hydroxyl groups, each of which connects with the carboxyl group of a fatty acid to form an ester linkage. Thus, every triacylglycerol (figure 5.12) contains three ester linkages, which makes it a triester.
Figure 5.12 Glycerol and triacylglycerol. Triacylglycerols, the largest energy depot in living organisms, are triesters of glycerol and fatty acids. R1, R2, and R3 represent the aliphatic chains of the fatty acids, which usually differ. Acyl groups are shown in color.
Because there is a great variety of available fatty acids, and because any of them can be linked to any of the hydroxyl groups of glycerol, we end up with an even greater variety of triacylglycerols. Chances are that there will be both saturated and unsaturated fatty acids present in a single triacylglycerol. Therefore, it is not accurate to state that a certain food contains only saturated or unsaturated fat. Instead, one should state that a certain food contains primarily saturated or unsaturated fatty acids.
Triacylglycerols are hydrophobic, which is evident by the immiscibility of fats or oils with water. Moreover, triacylglycerols have low thermal conductivity, rendering the subcutaneous fat of animals an efficient insulator of their internal organs against cold exposure.
The part of a fatty acid connected to an oxygen of glycerol in a triacylglycerol is called an acyl group. This is where the term tri-acyl-glycerol comes from; hence it is more accurate than triglyceride. The acyl groups derive from the ion of a fatty acid by removal of O-, and they bear the name of the fatty acid with the ending -oyl in place of -ate. Thus, the acyl group of palmitate is called the palmitoyl group.
The difference in melting point between saturated and unsaturated fatty acids described in the previous section is reflected in triacylglycerols: The more saturated acyl groups they contain, the higher their melting point is. Triacylglycerols of animal origin have a high content of saturated acyl groups, which is why animal fat is solid at room temperature. Conversely, plant triacylglycerols have a high content of unsaturated acyl groups, which is why vegetable oils are liquid in the same conditions.
Adaptations of the Vasculature to Training
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol.
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol. On top of these effects, endurance training contributes to lowering the risk of atherosclerosis by increasing HDL cholesterol.
In addition, the increases in blood flow and pressure accompanying exercise cause structural and functional adaptations of the vascular wall that lower the risk of atherosclerosis. These beneficial effects seem to be mediated by the endothelium, the single layer of cells lining the interior surface of the blood vessels, in direct contact with blood on the inside and surrounded by smooth muscle cells on the outside (figure 15.3).
Figure 15.3 How exercise elicits vasodilation. The increase in the pumping activity of the heart during exercise augments the shear stress on the endothelial cells lining the blood vessels. This mechanical stimulus leads to activation of eNOS, which catalyzes the synthesis of NO from arginine. NO diffuses to the smooth muscle cells forming the walls of blood vessels and activates soluble guanylate cyclase, which catalyzes the synthesis of cyclic GMP (cGMP) from GTP. Cyclic GMP activates PKG, leading to a drop in the cytosolic Ca2+ concentration, relaxation of the smooth muscle cells, and vasodilation.
The endothelial cells possess a variety of proteins that convert the mechanical stimulus of the exercise-induced increase in shear stress into chemical signals. In turn, these signals activate endothelial nitrogen oxide synthase (eNOS). This enzyme catalyzes the synthesis of nitric oxide (introduced in section 1.5) from arginine and oxygen in a reaction requiring NADPH as a reductant and yielding citrulline (the intermediate compound of the urea cycle introduced in section 12.9 and figure 12.10) in addition to NO.
NO diffuses out of the endothelial cells and enters neighboring smooth muscle cells, where it activates soluble guanylate cyclase, a cytosolic enzyme that catalyzes the formation of cyclic guanylate, or cyclic GMP (cGMP), from GTP, in a manner analogous to the synthesis of cAMP (section 10.6 and reaction 10.5).
Cyclic GMP, in turn, activates cGMP-dependent protein kinase, or PKG, which promotes smooth muscle relaxation by activating an ion pump that removes Ca2+ from the cytosol, thus preventing the interaction of myosin and actin. (Ca2+ allows myosin binding to actin in smooth muscle cells and skeletal muscle fibers through a series of interactions differing from the one described in section 8.10.) Smooth muscle relaxation results in dilation of the blood vessels, or vasodilation. The capacity of the vessels to dilate in response to increased blood flow, a property termed flow-mediated dilation, is considered an index of cardiovascular health.
As Green and coworkers review, training improves flow-mediated dilation—especially in individuals with or at risk of CVD—and reduces arterial wall stiffness by enhancing the endothelium-dependent signal transduction pathway described earlier. The enhancement includes higher eNOS content or activity. It is also possible that training influences other pathways of flow-mediated dilation. In addition, training increases the diameter of vessels—such as the coronary arteries, as well as arteries that nourish the exercising limbs—thus supplying more blood where it is needed. The stimulus, again, appears to be the increased shear stress imposed by blood on the endothelium with exercise.
Finally, training influences the smaller blood vessels: It increases the amount and diameter of the arterioles (the branches of arteries leading to capillaries) and muscle capillarization. The latter is measured as either the total number of capillaries in a muscle, or the number of capillaries per muscle fiber, or capillary density (defined in section 14.15 as the number of capillaries per unit of muscle cross-sectional area). Increased capillarization enhances the delivery of nutrients and O2 to muscle, as well as the uptake of muscle CO2 by blood.
Training-induced capillarization may be due to increased blood flow or to muscle activity itself. Both factors may promote the release of vascular endothelial growth factor (VEGF), a key angiogenic (that is, vessel-generating) protein, from muscle fibers. VEGF binds to the VEGF receptor in the plasma membrane of endothelial cells and activates a variety of signal transduction pathways, leading to endothelial cell proliferation and, hence, formation of new capillaries.
You can see that training provides more than one way of increasing blood supply to the active muscles. It seems that these beneficial adaptations can be elicited by endurance, resistance, and interval training. Improvements in vascular function with training are evident in both healthy humans and (possibly more evident) humans with or at risk of CVD.
Control of Muscle Activity by Ca2+
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered.
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered. Today we know that Ca2+ controls muscle activity and that it does so by permitting the binding of myosin to F-actin. This action of Ca2+ is not direct but indirect. As the Japanese physiologist Setsuro Ebashi discovered in the 1960s, control is exerted through tropomyosin and troponin, the two proteins that coexist with actin in the thin filaments, constituting about one third of the thin-filament mass. Let's meet them.
Tropomyosin has a molecular mass of 70 kDa and consists of two similar stringlike subunits in -helical conformation. The two subunits wind around each other just as the myosin heavy chains do in the myosin tail. The resulting extremely long tropomyosin molecules join in a row to form fibers. Two such fibers run along each thin filament while following the twisting of the actin monomers (figure 8.11).
Figure 8.11 Thin-filament proteins. A thin filament consists of an F-actin fiber (the double necklace of figure 8.7), two series of tropomyosin molecules, and troponin (Tn) complexes placed at regular intervals. Each troponin complex consists of TnC, which is the Ca2+ acceptor; TnI, which binds to actin; and TnT, which extends by way of a long tail along tropomyosin.
Adapted from L. Smillie and S. Ebashi, Essays in Biochemistry, vol. 10, edited by P.N. Campbell and F. Dickens (Orlando, FL: Academic, 1974), 1-35; C. Cohen Scientific America 233 (1975): 36 - 45. Courtesy of L. Smillie.
Troponin, symbolized as Tn, is a complex of three different subunits: TnC (18 kDa), TnI (24 kDa), and TnT (37 kDa). TnC binds Ca2+, TnI binds to actin, and TnT binds to tropomyosin. Two troponin complexes appear on the two sides of a thin filament every 39 nm, which is approximately the length of a tropomyosin molecule. One troponin complex attached to one tropomyosin molecule controls approximately seven actin monomers.
When a muscle is at rest (relaxed), the cytosol has a very low [Ca2+], approximately 10-7 mol · L-1. Researchers believe that, in this case, interactions among F-actin, TnI, TnT, and tropomyosin hold the latter close to the sites on the actin monomers where the myosin heads bind. Thus, tropomyosin hinders the interaction of thin and thick filaments. As we will see in the next section, muscle excitation by the nervous system results in the release of Ca2+ from an intracellular reservoir called the sarcoplasmic reticulum. This release causes a 100-fold surge in the cytosolic [Ca2+], from 10-7 to 10-5 mol · L-1.
The increased Ca2+ ions encounter TnC, bind to it, and elicit a change in its conformation. As a result, TnC detaches TnI from F-actin. This detachment lets tropomyosin move over the surface of the thin filament, away from the binding sites of myosin on F-actin. Myosin then binds to F-actin, and the muscle contracts. In fact, there is evidence that myosin binding to F-actin is cooperative; that is, the binding of some myosin heads facilitates the binding of additional ones by promoting the displacement of tropomyosin. This effect is reminiscent of the cooperative binding of O2 to hemoglobin (section 3.12).
Muscle activity continues until Ca2+ is sequestered in the sarcoplasmic reticulum (in a manner that we will examine shortly). The actin-TnI-TnT-tropomyosin interaction is then restored. Tropomyosin returns to a position hindering cross-bridge formation, and the muscle relaxes. The chain of events through which Ca2+ controls muscle contraction is summarized in figure 8.12.
Figure 8.12 Control of muscle contraction and relaxation by Ca2+. Ca2+ controls muscle contraction (left) and relaxation (right) through a series of protein interactions triggered by, respectively, Ca2+ release from and sequestration in the sarcoplasmic reticulum and involving troponin, tropomyosin, actin, and myosin.
What are triacylglycerols, and how do they serve us?
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils.
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils. Because of this abundance, they constitute 90% to 95% of dietary fat. In both animals and plants, triacylglycerols serve mainly as energy depots.
A triacylglycerol consists of a glycerol unit and three fatty acid units. Glycerol (figure 5.12), also known as glycerin or glycerine, is a compound of three carbons and three hydroxyl groups, each of which connects with the carboxyl group of a fatty acid to form an ester linkage. Thus, every triacylglycerol (figure 5.12) contains three ester linkages, which makes it a triester.
Figure 5.12 Glycerol and triacylglycerol. Triacylglycerols, the largest energy depot in living organisms, are triesters of glycerol and fatty acids. R1, R2, and R3 represent the aliphatic chains of the fatty acids, which usually differ. Acyl groups are shown in color.
Because there is a great variety of available fatty acids, and because any of them can be linked to any of the hydroxyl groups of glycerol, we end up with an even greater variety of triacylglycerols. Chances are that there will be both saturated and unsaturated fatty acids present in a single triacylglycerol. Therefore, it is not accurate to state that a certain food contains only saturated or unsaturated fat. Instead, one should state that a certain food contains primarily saturated or unsaturated fatty acids.
Triacylglycerols are hydrophobic, which is evident by the immiscibility of fats or oils with water. Moreover, triacylglycerols have low thermal conductivity, rendering the subcutaneous fat of animals an efficient insulator of their internal organs against cold exposure.
The part of a fatty acid connected to an oxygen of glycerol in a triacylglycerol is called an acyl group. This is where the term tri-acyl-glycerol comes from; hence it is more accurate than triglyceride. The acyl groups derive from the ion of a fatty acid by removal of O-, and they bear the name of the fatty acid with the ending -oyl in place of -ate. Thus, the acyl group of palmitate is called the palmitoyl group.
The difference in melting point between saturated and unsaturated fatty acids described in the previous section is reflected in triacylglycerols: The more saturated acyl groups they contain, the higher their melting point is. Triacylglycerols of animal origin have a high content of saturated acyl groups, which is why animal fat is solid at room temperature. Conversely, plant triacylglycerols have a high content of unsaturated acyl groups, which is why vegetable oils are liquid in the same conditions.
Adaptations of the Vasculature to Training
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol.
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol. On top of these effects, endurance training contributes to lowering the risk of atherosclerosis by increasing HDL cholesterol.
In addition, the increases in blood flow and pressure accompanying exercise cause structural and functional adaptations of the vascular wall that lower the risk of atherosclerosis. These beneficial effects seem to be mediated by the endothelium, the single layer of cells lining the interior surface of the blood vessels, in direct contact with blood on the inside and surrounded by smooth muscle cells on the outside (figure 15.3).
Figure 15.3 How exercise elicits vasodilation. The increase in the pumping activity of the heart during exercise augments the shear stress on the endothelial cells lining the blood vessels. This mechanical stimulus leads to activation of eNOS, which catalyzes the synthesis of NO from arginine. NO diffuses to the smooth muscle cells forming the walls of blood vessels and activates soluble guanylate cyclase, which catalyzes the synthesis of cyclic GMP (cGMP) from GTP. Cyclic GMP activates PKG, leading to a drop in the cytosolic Ca2+ concentration, relaxation of the smooth muscle cells, and vasodilation.
The endothelial cells possess a variety of proteins that convert the mechanical stimulus of the exercise-induced increase in shear stress into chemical signals. In turn, these signals activate endothelial nitrogen oxide synthase (eNOS). This enzyme catalyzes the synthesis of nitric oxide (introduced in section 1.5) from arginine and oxygen in a reaction requiring NADPH as a reductant and yielding citrulline (the intermediate compound of the urea cycle introduced in section 12.9 and figure 12.10) in addition to NO.
NO diffuses out of the endothelial cells and enters neighboring smooth muscle cells, where it activates soluble guanylate cyclase, a cytosolic enzyme that catalyzes the formation of cyclic guanylate, or cyclic GMP (cGMP), from GTP, in a manner analogous to the synthesis of cAMP (section 10.6 and reaction 10.5).
Cyclic GMP, in turn, activates cGMP-dependent protein kinase, or PKG, which promotes smooth muscle relaxation by activating an ion pump that removes Ca2+ from the cytosol, thus preventing the interaction of myosin and actin. (Ca2+ allows myosin binding to actin in smooth muscle cells and skeletal muscle fibers through a series of interactions differing from the one described in section 8.10.) Smooth muscle relaxation results in dilation of the blood vessels, or vasodilation. The capacity of the vessels to dilate in response to increased blood flow, a property termed flow-mediated dilation, is considered an index of cardiovascular health.
As Green and coworkers review, training improves flow-mediated dilation—especially in individuals with or at risk of CVD—and reduces arterial wall stiffness by enhancing the endothelium-dependent signal transduction pathway described earlier. The enhancement includes higher eNOS content or activity. It is also possible that training influences other pathways of flow-mediated dilation. In addition, training increases the diameter of vessels—such as the coronary arteries, as well as arteries that nourish the exercising limbs—thus supplying more blood where it is needed. The stimulus, again, appears to be the increased shear stress imposed by blood on the endothelium with exercise.
Finally, training influences the smaller blood vessels: It increases the amount and diameter of the arterioles (the branches of arteries leading to capillaries) and muscle capillarization. The latter is measured as either the total number of capillaries in a muscle, or the number of capillaries per muscle fiber, or capillary density (defined in section 14.15 as the number of capillaries per unit of muscle cross-sectional area). Increased capillarization enhances the delivery of nutrients and O2 to muscle, as well as the uptake of muscle CO2 by blood.
Training-induced capillarization may be due to increased blood flow or to muscle activity itself. Both factors may promote the release of vascular endothelial growth factor (VEGF), a key angiogenic (that is, vessel-generating) protein, from muscle fibers. VEGF binds to the VEGF receptor in the plasma membrane of endothelial cells and activates a variety of signal transduction pathways, leading to endothelial cell proliferation and, hence, formation of new capillaries.
You can see that training provides more than one way of increasing blood supply to the active muscles. It seems that these beneficial adaptations can be elicited by endurance, resistance, and interval training. Improvements in vascular function with training are evident in both healthy humans and (possibly more evident) humans with or at risk of CVD.
Control of Muscle Activity by Ca2+
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered.
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered. Today we know that Ca2+ controls muscle activity and that it does so by permitting the binding of myosin to F-actin. This action of Ca2+ is not direct but indirect. As the Japanese physiologist Setsuro Ebashi discovered in the 1960s, control is exerted through tropomyosin and troponin, the two proteins that coexist with actin in the thin filaments, constituting about one third of the thin-filament mass. Let's meet them.
Tropomyosin has a molecular mass of 70 kDa and consists of two similar stringlike subunits in -helical conformation. The two subunits wind around each other just as the myosin heavy chains do in the myosin tail. The resulting extremely long tropomyosin molecules join in a row to form fibers. Two such fibers run along each thin filament while following the twisting of the actin monomers (figure 8.11).
Figure 8.11 Thin-filament proteins. A thin filament consists of an F-actin fiber (the double necklace of figure 8.7), two series of tropomyosin molecules, and troponin (Tn) complexes placed at regular intervals. Each troponin complex consists of TnC, which is the Ca2+ acceptor; TnI, which binds to actin; and TnT, which extends by way of a long tail along tropomyosin.
Adapted from L. Smillie and S. Ebashi, Essays in Biochemistry, vol. 10, edited by P.N. Campbell and F. Dickens (Orlando, FL: Academic, 1974), 1-35; C. Cohen Scientific America 233 (1975): 36 - 45. Courtesy of L. Smillie.
Troponin, symbolized as Tn, is a complex of three different subunits: TnC (18 kDa), TnI (24 kDa), and TnT (37 kDa). TnC binds Ca2+, TnI binds to actin, and TnT binds to tropomyosin. Two troponin complexes appear on the two sides of a thin filament every 39 nm, which is approximately the length of a tropomyosin molecule. One troponin complex attached to one tropomyosin molecule controls approximately seven actin monomers.
When a muscle is at rest (relaxed), the cytosol has a very low [Ca2+], approximately 10-7 mol · L-1. Researchers believe that, in this case, interactions among F-actin, TnI, TnT, and tropomyosin hold the latter close to the sites on the actin monomers where the myosin heads bind. Thus, tropomyosin hinders the interaction of thin and thick filaments. As we will see in the next section, muscle excitation by the nervous system results in the release of Ca2+ from an intracellular reservoir called the sarcoplasmic reticulum. This release causes a 100-fold surge in the cytosolic [Ca2+], from 10-7 to 10-5 mol · L-1.
The increased Ca2+ ions encounter TnC, bind to it, and elicit a change in its conformation. As a result, TnC detaches TnI from F-actin. This detachment lets tropomyosin move over the surface of the thin filament, away from the binding sites of myosin on F-actin. Myosin then binds to F-actin, and the muscle contracts. In fact, there is evidence that myosin binding to F-actin is cooperative; that is, the binding of some myosin heads facilitates the binding of additional ones by promoting the displacement of tropomyosin. This effect is reminiscent of the cooperative binding of O2 to hemoglobin (section 3.12).
Muscle activity continues until Ca2+ is sequestered in the sarcoplasmic reticulum (in a manner that we will examine shortly). The actin-TnI-TnT-tropomyosin interaction is then restored. Tropomyosin returns to a position hindering cross-bridge formation, and the muscle relaxes. The chain of events through which Ca2+ controls muscle contraction is summarized in figure 8.12.
Figure 8.12 Control of muscle contraction and relaxation by Ca2+. Ca2+ controls muscle contraction (left) and relaxation (right) through a series of protein interactions triggered by, respectively, Ca2+ release from and sequestration in the sarcoplasmic reticulum and involving troponin, tropomyosin, actin, and myosin.
What are triacylglycerols, and how do they serve us?
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils.
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils. Because of this abundance, they constitute 90% to 95% of dietary fat. In both animals and plants, triacylglycerols serve mainly as energy depots.
A triacylglycerol consists of a glycerol unit and three fatty acid units. Glycerol (figure 5.12), also known as glycerin or glycerine, is a compound of three carbons and three hydroxyl groups, each of which connects with the carboxyl group of a fatty acid to form an ester linkage. Thus, every triacylglycerol (figure 5.12) contains three ester linkages, which makes it a triester.
Figure 5.12 Glycerol and triacylglycerol. Triacylglycerols, the largest energy depot in living organisms, are triesters of glycerol and fatty acids. R1, R2, and R3 represent the aliphatic chains of the fatty acids, which usually differ. Acyl groups are shown in color.
Because there is a great variety of available fatty acids, and because any of them can be linked to any of the hydroxyl groups of glycerol, we end up with an even greater variety of triacylglycerols. Chances are that there will be both saturated and unsaturated fatty acids present in a single triacylglycerol. Therefore, it is not accurate to state that a certain food contains only saturated or unsaturated fat. Instead, one should state that a certain food contains primarily saturated or unsaturated fatty acids.
Triacylglycerols are hydrophobic, which is evident by the immiscibility of fats or oils with water. Moreover, triacylglycerols have low thermal conductivity, rendering the subcutaneous fat of animals an efficient insulator of their internal organs against cold exposure.
The part of a fatty acid connected to an oxygen of glycerol in a triacylglycerol is called an acyl group. This is where the term tri-acyl-glycerol comes from; hence it is more accurate than triglyceride. The acyl groups derive from the ion of a fatty acid by removal of O-, and they bear the name of the fatty acid with the ending -oyl in place of -ate. Thus, the acyl group of palmitate is called the palmitoyl group.
The difference in melting point between saturated and unsaturated fatty acids described in the previous section is reflected in triacylglycerols: The more saturated acyl groups they contain, the higher their melting point is. Triacylglycerols of animal origin have a high content of saturated acyl groups, which is why animal fat is solid at room temperature. Conversely, plant triacylglycerols have a high content of unsaturated acyl groups, which is why vegetable oils are liquid in the same conditions.
Adaptations of the Vasculature to Training
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol.
Training benefits the blood vessels as well as the heart. As discussed in sections 11.21 and 11.22, endurance and resistance training can lower the risk of atherosclerosis by decreasing plasma triacylglycerols, total cholesterol, and LDL cholesterol. On top of these effects, endurance training contributes to lowering the risk of atherosclerosis by increasing HDL cholesterol.
In addition, the increases in blood flow and pressure accompanying exercise cause structural and functional adaptations of the vascular wall that lower the risk of atherosclerosis. These beneficial effects seem to be mediated by the endothelium, the single layer of cells lining the interior surface of the blood vessels, in direct contact with blood on the inside and surrounded by smooth muscle cells on the outside (figure 15.3).
Figure 15.3 How exercise elicits vasodilation. The increase in the pumping activity of the heart during exercise augments the shear stress on the endothelial cells lining the blood vessels. This mechanical stimulus leads to activation of eNOS, which catalyzes the synthesis of NO from arginine. NO diffuses to the smooth muscle cells forming the walls of blood vessels and activates soluble guanylate cyclase, which catalyzes the synthesis of cyclic GMP (cGMP) from GTP. Cyclic GMP activates PKG, leading to a drop in the cytosolic Ca2+ concentration, relaxation of the smooth muscle cells, and vasodilation.
The endothelial cells possess a variety of proteins that convert the mechanical stimulus of the exercise-induced increase in shear stress into chemical signals. In turn, these signals activate endothelial nitrogen oxide synthase (eNOS). This enzyme catalyzes the synthesis of nitric oxide (introduced in section 1.5) from arginine and oxygen in a reaction requiring NADPH as a reductant and yielding citrulline (the intermediate compound of the urea cycle introduced in section 12.9 and figure 12.10) in addition to NO.
NO diffuses out of the endothelial cells and enters neighboring smooth muscle cells, where it activates soluble guanylate cyclase, a cytosolic enzyme that catalyzes the formation of cyclic guanylate, or cyclic GMP (cGMP), from GTP, in a manner analogous to the synthesis of cAMP (section 10.6 and reaction 10.5).
Cyclic GMP, in turn, activates cGMP-dependent protein kinase, or PKG, which promotes smooth muscle relaxation by activating an ion pump that removes Ca2+ from the cytosol, thus preventing the interaction of myosin and actin. (Ca2+ allows myosin binding to actin in smooth muscle cells and skeletal muscle fibers through a series of interactions differing from the one described in section 8.10.) Smooth muscle relaxation results in dilation of the blood vessels, or vasodilation. The capacity of the vessels to dilate in response to increased blood flow, a property termed flow-mediated dilation, is considered an index of cardiovascular health.
As Green and coworkers review, training improves flow-mediated dilation—especially in individuals with or at risk of CVD—and reduces arterial wall stiffness by enhancing the endothelium-dependent signal transduction pathway described earlier. The enhancement includes higher eNOS content or activity. It is also possible that training influences other pathways of flow-mediated dilation. In addition, training increases the diameter of vessels—such as the coronary arteries, as well as arteries that nourish the exercising limbs—thus supplying more blood where it is needed. The stimulus, again, appears to be the increased shear stress imposed by blood on the endothelium with exercise.
Finally, training influences the smaller blood vessels: It increases the amount and diameter of the arterioles (the branches of arteries leading to capillaries) and muscle capillarization. The latter is measured as either the total number of capillaries in a muscle, or the number of capillaries per muscle fiber, or capillary density (defined in section 14.15 as the number of capillaries per unit of muscle cross-sectional area). Increased capillarization enhances the delivery of nutrients and O2 to muscle, as well as the uptake of muscle CO2 by blood.
Training-induced capillarization may be due to increased blood flow or to muscle activity itself. Both factors may promote the release of vascular endothelial growth factor (VEGF), a key angiogenic (that is, vessel-generating) protein, from muscle fibers. VEGF binds to the VEGF receptor in the plasma membrane of endothelial cells and activates a variety of signal transduction pathways, leading to endothelial cell proliferation and, hence, formation of new capillaries.
You can see that training provides more than one way of increasing blood supply to the active muscles. It seems that these beneficial adaptations can be elicited by endurance, resistance, and interval training. Improvements in vascular function with training are evident in both healthy humans and (possibly more evident) humans with or at risk of CVD.
Control of Muscle Activity by Ca2+
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered.
For more than 130 years (since 1883), it has been known that muscles cannot contract in the absence of calcium cations. However, 80 years had to pass before the exact role of Ca2+ was discovered. Today we know that Ca2+ controls muscle activity and that it does so by permitting the binding of myosin to F-actin. This action of Ca2+ is not direct but indirect. As the Japanese physiologist Setsuro Ebashi discovered in the 1960s, control is exerted through tropomyosin and troponin, the two proteins that coexist with actin in the thin filaments, constituting about one third of the thin-filament mass. Let's meet them.
Tropomyosin has a molecular mass of 70 kDa and consists of two similar stringlike subunits in -helical conformation. The two subunits wind around each other just as the myosin heavy chains do in the myosin tail. The resulting extremely long tropomyosin molecules join in a row to form fibers. Two such fibers run along each thin filament while following the twisting of the actin monomers (figure 8.11).
Figure 8.11 Thin-filament proteins. A thin filament consists of an F-actin fiber (the double necklace of figure 8.7), two series of tropomyosin molecules, and troponin (Tn) complexes placed at regular intervals. Each troponin complex consists of TnC, which is the Ca2+ acceptor; TnI, which binds to actin; and TnT, which extends by way of a long tail along tropomyosin.
Adapted from L. Smillie and S. Ebashi, Essays in Biochemistry, vol. 10, edited by P.N. Campbell and F. Dickens (Orlando, FL: Academic, 1974), 1-35; C. Cohen Scientific America 233 (1975): 36 - 45. Courtesy of L. Smillie.
Troponin, symbolized as Tn, is a complex of three different subunits: TnC (18 kDa), TnI (24 kDa), and TnT (37 kDa). TnC binds Ca2+, TnI binds to actin, and TnT binds to tropomyosin. Two troponin complexes appear on the two sides of a thin filament every 39 nm, which is approximately the length of a tropomyosin molecule. One troponin complex attached to one tropomyosin molecule controls approximately seven actin monomers.
When a muscle is at rest (relaxed), the cytosol has a very low [Ca2+], approximately 10-7 mol · L-1. Researchers believe that, in this case, interactions among F-actin, TnI, TnT, and tropomyosin hold the latter close to the sites on the actin monomers where the myosin heads bind. Thus, tropomyosin hinders the interaction of thin and thick filaments. As we will see in the next section, muscle excitation by the nervous system results in the release of Ca2+ from an intracellular reservoir called the sarcoplasmic reticulum. This release causes a 100-fold surge in the cytosolic [Ca2+], from 10-7 to 10-5 mol · L-1.
The increased Ca2+ ions encounter TnC, bind to it, and elicit a change in its conformation. As a result, TnC detaches TnI from F-actin. This detachment lets tropomyosin move over the surface of the thin filament, away from the binding sites of myosin on F-actin. Myosin then binds to F-actin, and the muscle contracts. In fact, there is evidence that myosin binding to F-actin is cooperative; that is, the binding of some myosin heads facilitates the binding of additional ones by promoting the displacement of tropomyosin. This effect is reminiscent of the cooperative binding of O2 to hemoglobin (section 3.12).
Muscle activity continues until Ca2+ is sequestered in the sarcoplasmic reticulum (in a manner that we will examine shortly). The actin-TnI-TnT-tropomyosin interaction is then restored. Tropomyosin returns to a position hindering cross-bridge formation, and the muscle relaxes. The chain of events through which Ca2+ controls muscle contraction is summarized in figure 8.12.
Figure 8.12 Control of muscle contraction and relaxation by Ca2+. Ca2+ controls muscle contraction (left) and relaxation (right) through a series of protein interactions triggered by, respectively, Ca2+ release from and sequestration in the sarcoplasmic reticulum and involving troponin, tropomyosin, actin, and myosin.
What are triacylglycerols, and how do they serve us?
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils.
Triacylglycerols, or triglycerides, are the most abundant lipid category. They are the main components of animal (including human) fat, most of which is concentrated in adipose tissue; they are also the main components of vegetable oils. Because of this abundance, they constitute 90% to 95% of dietary fat. In both animals and plants, triacylglycerols serve mainly as energy depots.
A triacylglycerol consists of a glycerol unit and three fatty acid units. Glycerol (figure 5.12), also known as glycerin or glycerine, is a compound of three carbons and three hydroxyl groups, each of which connects with the carboxyl group of a fatty acid to form an ester linkage. Thus, every triacylglycerol (figure 5.12) contains three ester linkages, which makes it a triester.
Figure 5.12 Glycerol and triacylglycerol. Triacylglycerols, the largest energy depot in living organisms, are triesters of glycerol and fatty acids. R1, R2, and R3 represent the aliphatic chains of the fatty acids, which usually differ. Acyl groups are shown in color.
Because there is a great variety of available fatty acids, and because any of them can be linked to any of the hydroxyl groups of glycerol, we end up with an even greater variety of triacylglycerols. Chances are that there will be both saturated and unsaturated fatty acids present in a single triacylglycerol. Therefore, it is not accurate to state that a certain food contains only saturated or unsaturated fat. Instead, one should state that a certain food contains primarily saturated or unsaturated fatty acids.
Triacylglycerols are hydrophobic, which is evident by the immiscibility of fats or oils with water. Moreover, triacylglycerols have low thermal conductivity, rendering the subcutaneous fat of animals an efficient insulator of their internal organs against cold exposure.
The part of a fatty acid connected to an oxygen of glycerol in a triacylglycerol is called an acyl group. This is where the term tri-acyl-glycerol comes from; hence it is more accurate than triglyceride. The acyl groups derive from the ion of a fatty acid by removal of O-, and they bear the name of the fatty acid with the ending -oyl in place of -ate. Thus, the acyl group of palmitate is called the palmitoyl group.
The difference in melting point between saturated and unsaturated fatty acids described in the previous section is reflected in triacylglycerols: The more saturated acyl groups they contain, the higher their melting point is. Triacylglycerols of animal origin have a high content of saturated acyl groups, which is why animal fat is solid at room temperature. Conversely, plant triacylglycerols have a high content of unsaturated acyl groups, which is why vegetable oils are liquid in the same conditions.
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