and Exercise Metabolism

All brand names and product names used in this book are trade names, service marks, trademarks, or registered trademarks of their respective owners. Summary: "This book will provide them with the basics of the subject presented in a clear and accessible style firmly set within a sporting context" - Provided by the publisher.

Preface

We both feel that we need to provide a textbook dedicated to sports and exercise science students who want to gain a solid (not necessarily comprehensive) understanding of key aspects in biochemistry – especially those related to energy metabolism. In our experience, students of sport and exercise science learn better when their genuine interest in sport and exercise dominates the conversation.

Part One

Basic Muscle Physiology and Energetics

Energy sources for muscular activity

Learning outcomes

Key words

Adenosine triphosphate

• Energy continuum
• Energy supply for muscle contraction
• Energy systems and running speed
• Why can’t a marathon be sprinted?
• Energy sources and muscle
• Can muscle use protein for energy?
• Key points

Another way of expressing the energy continuum is presented in Figure 1.3, which shows the main sources of energy for running events at different distances. In Figure 1.5, you should also note that PCr is rapidly lost during intense exercise and quickly recovered (it may even become depleted if the exercise is sufficiently intense or prolonged).

Figure 1.1 Adenosine triphosphate (ATP)

Skeletal muscle structure and function

• Skeletal muscle structure
• Gross anatomical structure
• The muscle fibre
• Muscle contraction
• Propagation of the action potential In order for muscle fibres to contract, an action
• Excitation-contraction coupling
• The sliding filament mechanism
• Muscle fibre types
• General classification of muscle fibres Generally speaking, human muscle fibres can be
• Muscle fibre distribution
• Muscle fibre recruitment
• Muscles in action
• Types of muscle contraction
• The twitch contraction
• The length-tension relationship
• Tetanus contractions
• Force-velocity relationship
• Muscle fatigue
• Key points

Myofibrils can be considered the contractile apparatus of the muscle fiber as they contain the contractile proteins actin and myosin. As a result, the overall length of the sarcomere is shortened and thus the muscle fiber contracts.

Figure 2.1 Gross anatomical structure of skeletal muscle. (From Tortora and Derrickson, Principles of Anatomy and Physiology, Twelfth Edition, 2009, reproduced by permission of John Wiley & Sons Inc.)

Biochemical concepts

Organization of matter

• Matter and elements
• Atoms and atomic structure
• Atomic number and mass number What makes the atoms of one element different
• Atomic mass
• Ions, molecules, compounds and macronutrients

Rounded to the nearest whole number, the atomic mass of an element generally coincides with the mass number of the predominant isotope of that element (see Figure 3.2). Mass number = number of protons and neutrons in an atom (bold indicates the most common isotope).

Table 3.1 An overview of the body’s main chemical elements and some of their known functions

Chemical bonding

• Ionic bonds
• Covalent bonds
• Molecular formulae and structures In briefly recapping what we have covered so
• Functional groups

When two or more atoms of the same element form a covalent bond, it is always nonpolar. Note that we begin this process by multiplying the atomic mass of the element by the number of atoms present in the compound.

Figure 3.3 The basic flow of matter. Atoms of elements such as oxygen, carbon, hydrogen and nitrogen ultimately combine to make biomolecules, examples of which include the foodstuffs and fluids that we eat and drink in order to fuel our muscles during exerci

Chemical reactions, ATP and energy

• Energy
• Units of energy
• Types of chemical reactions

In such circumstances, the energy produced can then be stored within the covalent bonds of a compound known as adenosine triphosphate (ATP). In this case, the energy is provided by breaking the bonds in compounds such as carbohydrates, fats and proteins.

Figure 3.8 Schematic illustration of the coupling between exergonic (energy-liberating) and endergonic (energy-consuming) chemical reactions

Misconception

Water

• General functions of water
• Water as a solvent

Although, strictly speaking, redox reactions involve the transfer of electrons, the most common form of redox reaction involves the exchange of hydrogen atoms between molecules (where the molecule is oxidized, the reaction can therefore be further classified as a dehydrogenation reaction). This makes water an excellent solvent for other ionic or polar substances (solutes), as the slightly negatively charged oxygen atoms and the slightly positively charged hydrogen atoms are attracted to other charged substances.

Solutions and concentrations

Another important function of water for exercise metabolism is related to chemical reactions, as water serves as a medium for most chemical reactions in the body (e.g. hydrolysis of ATP) and also participates as a reactant or product in certain reactions (e.g. formation of peptide bonds in protein synthesis ). Another important function of water is to act as a solvent that can dissolve another substance called a solute to make a solution.

Laboratory focus – making concentrated solutions

Acid-base balance

• Acids, bases and salts

Similarly, the atomic mass of water is 18, which means that 1 mole of water is equivalent to 18 grams of water, which is equivalent to 6.023×1023 molecules. Examples of acids in our bodies include hydrochloric acid (HCl), carbonic acid (H2CO3) and lactic acid (C3H6O3), the latter of which we produce in our muscles during high-intensity exercise (Karlsson & Saltin, 1970).

Misconception: lactic acid and lactate are not the same thing!

• pH Scale
• Buffers
• Cell structure
• The plasma membrane
• The nucleus
• Cytoplasm and organelles
• Key points

When two or more tissues are combined, the result is an organ (eg the stomach), which in turn can also. Ultimately, when all the systems (eg, digestive, nervous, cardiovascular, musculoskeletal, etc.) are in place and working together, the result is a living organism—for example, the person reading this book. The intermediate filament desmin is also important as it helps to 'anchor' the contractile proteins and organelles such as the mitochondria and nucleus in place.

Figure 3.10 The pH scale. Note that a pH of 7.0 is referred to as neutral. The normal resting pH of arterial blood is 7.4 and that of muscle is 7.1

Part Two

Fundamentals of Sport and Exercise Biochemistry

Proteins

Protein function

• General protein function

The term proteome refers to all the proteins present in a cell, and many scientists are dedicated to describing the function of all the proteins present in the proteome. For example, when a signal has been triggered (ie the first domino has been knocked over), this leads to a chain of dominoes repeatedly collapsing until the required response is achieved. The importance of the dystrophin protein is evident from a review of patients with Duchenne muscular dystrophy (Kunkel, 1986).

Figure 4.1 Schematic illustration of the diverse functions of proteins

Amino acids

• Amino acid structure

Protein structure

• Primary structure
• Secondary structure
• Tertiary structure
• Quaternary structure

Depending on the number of amino acids present in the peptide chain, we can use prefixes to characterize the number present. Indeed, this combination can exist as 20n alternatives, where n refers to the number of amino acids present in the polypeptide chain. Given the tertiary three-dimensional shape, it is possible for amino acids that are far apart in the primary structure to be in close proximity.

Figure 4.3 The specific structure of each of the 20 amino acids

Proteins as enzymes

• Mechanisms of enzyme action
• Factors affecting rates of enzymatic reactions
• Coenzymes and cofactors
• Classification of enzymes
• Regulation of enzyme activity

In example (a), the enzyme and substrate fit in a similar way to how a key fits in a lock. For example, the enzyme creatine kinase has phosphocreatine (PCr) as a substrate and, as a kinase, transfers a phosphate group to ADP, creating the products ATP and creatine (Cr). Such processes change the conformation of the enzyme and are known as phosphorylation (addition of phosphate) or dephosphorylation (removal of phosphate).

Figure 4.8 Enzyme and substrate binding to form the enzyme substrate complex. In example (a), the enzyme and substrate fit similar as to a how a key fits in a lock.

Protein turnover

• Overview of protein turnover
• DNA structure
• Transcription
• The genetic code
• Translation

For this to happen, the bases in the mRNA molecule are read in groups of three known as codons. Finally, translation will stop when one of the stop codons on the mRNA strand is reached. The sequence of bases in the mRNA strand is identical to that in the sense strand, except that U replaces T.

Figure 4.15 The pathway from DNA to protein

Amino acid metabolism

• Free amino acid pool
• Transamination
• Deamination
• Branched chain amino acids
• Glucose-alanine cycle
• Glutamine
• The urea cycle

This free amino acid pool can also be supplemented by the supply of amino acids catabolized from the breakdown of intracellular proteins. The initial stage of breakdown of amino acids is the removal of nitrogen by removing the α-amino group. Collectively, these amino acids are known as the branched-chain amino acids (BCAAs) and are so named because of their aliphatic side chains (meaning the carbon atoms in their side chain are linked together in branch-like chains).

Figure 4.20 A basic overview of amino acid metabolism, showing the continual exchange of amino acids between the amino acid pool and tissues

Key points

As we conclude our study of amino acid metabolism, you should now appreciate that virtually all of the nitrogen that is broken down from the amino groups of α-amino acids is ultimately converted to ammonia in the liver. It is important to note that aspartate is the only amino acid that directly disposes of its amino group in the urea cycle. The free amino acid pool represents the amino acids present in the blood and the extracellular fluid in tissues.

Carbohydrates

Relevance of carbohydrates for sport and exercise

The evidence for the importance of carbohydrates and performance can be seen in Figure 5.1, where the relationship between exercise intensity and muscle glycogen depletion is highlighted. It seems clear that there is a correlation between diet and muscle glycogen content, and also between muscle glycogen content and the ability to exercise for longer periods of time. Muscle glycogen was significantly depleted at half-time, and almost completely at the end of the bout, indicating significant muscle carbohydrate use.

Figure 5.2 Evidence of hypoglycaemia during pro- pro-longed exercise (adapted from Christensen and Hansen, 1936)

Types and structure of carbohydrates

• Monosaccharides
• Disaccharides and polysaccharides When two monosaccharides are attached together,

Examples of the glycosidic bonds for the disaccharides maltose and sucrose are shown in Figure 5.10. Because amylopectin is more branched than amylose, it is the major storage form of carbohydrates in some of the foods we eat, such as potato, rice, wheat and corn (Figure 5.12a and Table 5.2). Glycogen, the storage form of carbohydrates in the muscle and liver of animals, is much more branched than amylopectin (Figure 5.12b).

Figure 5.5 Isomers of glucose

Metabolism of carbohydrates

• Glycogenolysis
• Glycolysis
• Lactate metabolism
• The ‘link’ reaction; production of acetyl-CoA
• The TCA (or Krebs) cycle
• Electron transport chain
• Oxidative phosphorylation
• Calculation of ATP generated in glucose oxidation
• Overview of glucose oxidation
• Fructose metabolism
• Gluconeogenesis
• Glycogenesis

Note that the processes begin in the cytoplasm (so they are called anaerobic, because no oxygen is required) and then complete in the mitochondria (a so-called aerobic process). The combination of the four-carbon OAA and the two-carbon acetyl-CoA results in the formation of the six-carbon citric acid (or citrate). This process results in the conversion of ADP to ATP and is known as oxidative phosphorylation.

Figure 5.10 Glycoside bond in the formation of the disaccharides, maltose and sucrose

Key points

In Chapter 7 we investigate how glycogen synthase is regulated in relation to phosphorylase, the enzyme that breaks down glycogen.

Lipids

• Relevance of lipids for sport and exercise
• Structure of lipids
• Classification of lipids
• Compound lipids
• Derived lipids
• Metabolism of lipids
• Lipolysis
• β-oxidation
• Ketone body formation
• Formation of fatty acids
• Triglyceride synthesis
• Key points

The greater the presence of fatty acid transporters in the membrane, the greater the uptake of fatty acids into the cell. Fatty acid synthesis occurs in the cytoplasm, in contrast to the oxidation of fatty acids (β-oxidation), which takes place in the mitochondria. The synthesis of fatty acids from acetyl-CoA and malonyl-CoA is carried out in the cytoplasm by a large complex enzyme, fatty acid synthase (FAS).

Figure 6.2 demonstrates the importance of lipids as energy sources during exercise of increasing intensity

Part Three

Metabolic Regulation in Sport and Exercise

Principles of metabolic regulation

• How are catabolic and anabolic reactions controlled?
• Hormones
• Peptide hormones, neurotransmitters
• Adrenaline activation of glycogenolysis Adrenaline, a hormone secreted from the adrenal
• Adrenaline activation of lipolysis During exercise, an increase in circulating
• Insulin activation of glycogen synthase During recovery from exercise, and after con-
• Insulin inhibition of lipolysis
• Insulin stimulation of protein synthesis The stimulation of protein synthesis is a classic,
• Steroid hormones and regulation
• Allosteric effectors
• Regulation of glycogen phosphorylase As we have already seen, glycogen phospho-
• Regulation of PFK
• Regulation of PDH
• Regulation of CPT1
• AMPK as a metabolic regulator
• Key points

Most of the enzymes involved in the energy-producing and energy-storing processes exist in two forms, i.e. Consequently, they affect their target cells by attaching to receptors on the surface of the cell membrane and thereby influencing the cell. The binding of insulin to the outer subunits of the receptor causes a conformational change in the membrane-spanning subunit, which is also an enzyme (a tyrosine kinase).

Table 7.1 Hormones, the major tissue secreted from, their target tissue, and their effect on various biochemical processes

High-intensity exercise

• Overview of energy production and metabolic regulation in
• Definition of high-intensity exercise High-intensity exercise (HIE) can be defined as
• Energy production during high-intensity exercise
• Evidence of energy sources used in HIE An early study using electrical stimulation and
• Metabolic regulation during high-intensity exercise
• Effects of exercise duration
• Effects of nutritional status
• Can nutritional ergogenic aids help HIE?
• Effects of training
• Mechanisms of fatigue
• Reduced ATP
• Reduced PCr
• Increased P i
• Lactate and H +
• Key points

Indirect estimates of the anaerobic and aerobic contributions to intense 30-second isolated knee extension exercise are 80% and 20%, respectively (Bangsbo et al., 1990). Although the evidence seems promising, Ball et al. 1996) found that correction of the acidotic state does not normalize performance. HIE exercise in trained subjects elevates the expression of the Na + /K + pump subunits (Iaia & Bangsbo, 2011).

Figure 8.1 Oxygen deficit during steady state exercise

Endurance exercise

Overview of energy production and metabolic regulation in

• Definition and models of endurance exercise
• Energy production in endurance exercise
• Overview of metabolic regulation in endurance exercise

Both fuel sources can be provided by extra-muscular sources such as plasma FFAs (derived from adipose tissue lipolysis) or plasma glucose (provided by liver glycogen or glucose originating from the gastrointestinal tract). Alternatively, substrates can be provided from intramuscular sources such as muscle glycogen or intramuscular triglycerides. A schematic overview of the main sources and pathways involved in CHO and lipid metabolism is shown in Figure 9.1.

Figure 9.1 Schematic overview of energy producing pathways in skeletal muscle related to CHO and lipid metabolism

Effects of exercise intensity

• CHO metabolism
• Lipid metabolism

However, the percentage of phosphorylase in the more active form does not appear to increase with exercise intensity and is in fact reduced after just ten minutes of intense exercise (see Figure 9.3), which may be related to the reduced pH. associated with intensive exercise (Howlett et al., 1998). Although glucose uptake is also regulated by GLUT4 levels, it is unlikely that GLUT4 plays a role in this situation, as GLUT4 translocation to the plasma membrane does not increase with exercise intensity (Kraniou et al., 2006). In a follow-up study, Romijn et al. 1995) tested the hypothesis that the reduced availability of free fatty acids in plasma is limited to the lipid oxidation rate during intensive exercise by intravenous infusion of lipids and heparin during exercise at 85% VO2max.

Effects of exercise duration

Furthermore, there is a strong positive and negative correlation with the concentration of acetyl carnitine and RER and the rate of fat oxidation, respectively, as shown in Figure 9.10. Based on these data, a proposed model for carnitine-mediated regulation of lipid oxidation is depicted in Figure 9.11. The down-regulation of PDH activity as the duration of exercise progresses (see Figure 9.14) may be due to reduced pyruvate flux, thereby reducing production of the substrate required for the PDH reaction.

Effects of nutritional status

• CHO-loading and muscle glycogen availability
• Fat-loading strategies
• Pre-exercise and during-exercise CHO ingestion
• Pre-exercise FFA availability

VO2max starts with low (LCHO) or high pre-exercise glycogen (HCHO) concentrations, CL indicates citrate lyase (adapted from Roepstorffet al., 2005). Consequently, lipid oxidation during exercise is higher with LGI CHO intake, compared to HGI intake, and muscle glycogen utilization is reduced (Weeet al., 2005). However, whether or not caffeine increases lipid oxidation during exercise remains a controversial issue, and interested readers are directed to relevant reviews in the area (Grahamet al., 2008).

Effects of training status

• CHO metabolism
• Lipid metabolism

Furthermore, exercise performance (a 10 km time trial performed after the 90 min of steady state exercise) was not enhanced by the high-fat meal compared to an isoenergetic high-CHO meal. Athletes should also be careful about choosing high-fat meals before exercise because of the problems associated with digestion after consuming meals that consist largely of long-chain triglycerides (Horowitz & Klein, 2000).