Bioenergetic systems

Last updated January 23, 2024

Bioenergetic systems are metabolic processes that relate to the flow of energy in living organisms. Those processes convert energy into adenosine triphosphate (ATP), which is the form suitable for muscular activity. There are two main forms of synthesis of ATP: aerobic, which uses oxygen from the bloodstream, and anaerobic, which does not. Bioenergetics is the field of biology that studies bioenergetic systems.

Overview
Adenosine triphosphate
Coupled reactions
Anaerobic and aerobic metabolism
Anaerobic metabolism
ATP–CP: the phosphagen system
Anaerobic glycolysis
Aerobic metabolism
Aerobic glycolysis
Fatty acid oxidation
Amino acid degradation
Purine nucleotide cycle
Ketolysis
Ethanol metabolism
See also
References
Further reading

Overview

The process that converts the chemical energy of food into ATP (which can release energy) is not dependent on oxygen availability. During exercise, the supply and demand of oxygen available to muscle cells is affected by duration and intensity and by the individual's cardio respiratory fitness level.^[1] It is also affected by the type of activity, for instance, during isometric activity the contracted muscles restricts blood flow (leaving oxygen and blood borne fuels unable to be delivered to muscle cells adequately for oxidative phosphorylation).^[2]^[3] Three systems can be selectively recruited, depending on the amount of oxygen available, as part of the cellular respiration process to generate ATP for the muscles. They are ATP, the anaerobic system and the aerobic system.

Adenosine triphosphate

ATP is the only type of usable form of chemical energy for musculoskeletal activity. It is stored in most cells, particularly in muscle cells. Other forms of chemical energy, such as those available from oxygen and food, must be transformed into ATP before they can be utilized by the muscle cells.^[4]

Coupled reactions

Since energy is released when ATP is broken down, energy is required to rebuild or resynthesize it. The building blocks of ATP synthesis are the by-products of its breakdown; adenosine diphosphate (ADP) and inorganic phosphate (P_i). The energy for ATP resynthesis comes from three different series of chemical reactions that take place within the body. Two of the three depend upon the food eaten, whereas the other depends upon a chemical compound called phosphocreatine. The energy released from any of these three series of reactions is utilized in reactions that resynthesize ATP. The separate reactions are functionally linked in such a way that the energy released by one is used by the other.^[4]^: 8–9

Three processes can synthesize ATP:

ATP–CP system (phosphagen system) – At maximum intensity, this system is used for up to 10–15 seconds.^[5] The ATP–CP system neither uses oxygen nor produces lactic acid if oxygen is unavailable and is thus called alactic anaerobic. This is the primary system behind very short, powerful movements like a golf swing, a 100 m sprint or powerlifting.
Anaerobic system – This system predominates in supplying energy for intense exercise lasting less than two minutes. It is also known as the glycolytic system. An example of an activity of the intensity and duration that this system works under would be a 400 m sprint.
Aerobic system – This is the long-duration energy system. After five minutes of exercise, the O₂ system is dominant. In a 1 km run, this system is already providing approximately half the energy; in a marathon run it provides 98% or more.^[6] Around mile 20 of a marathon, runners typically "hit the wall," having depleted their glycogen reserves they then attain "second wind" which is entirely aerobic metabolism primarily by free fatty acids.^[7]

Aerobic and anaerobic systems usually work concurrently. When describing activity, it is not a question of which energy system is working, but which predominates.^[1]^[8]

Exercise intensity (%W_max) and substrate use in muscle during aerobic activity (cycling)^[1]
		At rest	40%W_max Very low-intensity	55%W_max Low-intensity	75%W_max Moderate-intensity
		Exercise intensity (W_Max)
Percent of substrate contribution to total energy expenditure	Plasma glucose	44%	10%	13%	18%
	Muscle glycogen	-	35%	38%	58%
	Plasma free fatty acids	56%	31%	25%	15%
	Other fat sources (intramuscular andlipoprotein-derived triglycerides)	-	24%	24%	9%
	Total	100%	100%	100%	100%
Total energy expenditure (kJ min⁻¹)		10	50	65	85

Anaerobic and aerobic metabolism

The term metabolism refers to the various series of chemical reactions that take place within the body. Aerobic refers to the presence of oxygen, whereas anaerobic means with a series of chemical reactions that does not require the presence of oxygen. The ATP-CP series and the lactic acid series are anaerobic, whereas the oxygen series is aerobic.^[4]^: 9

Anaerobic metabolism

ATP–CP: the phosphagen system

(A) Phosphocreatine, which is stored in muscle cells, contains a high energy bond. (B) When creatine phosphate is broken down during muscular contraction, energy is released and utilized to resynthesize ATP. ATP-PC.jpg — (A) Phosphocreatine, which is stored in muscle cells, contains a high energy bond. (B) When creatine phosphate is broken down during muscular contraction, energy is released and utilized to resynthesize ATP.

Creatine phosphate (CP), like ATP, is stored in muscle cells. When it is broken down, a considerable amount of energy is released. The energy released is coupled to the energy requirement necessary for the resynthesis of ATP.

The total muscular stores of both ATP and CP are small. Thus, the amount of energy obtainable through this system is limited. The phosphagen stored in the working muscles is typically exhausted in seconds of vigorous activity. However, the usefulness of the ATP-CP system lies in the rapid availability of energy rather than quantity. This is important with respect to the kinds of physical activities that humans are capable of performing.^[4]^: 9–11

The phosphagen system (ATP-PCr) occurs in the cytosol (a gel-like substance) of the sarcoplasm of skeletal muscle, and in the myocyte's cytosolic compartment of the cytoplasm of cardiac and smooth muscle.^[9]

During muscle contraction:

H₂O + ATP → H⁺ + ADP + P_i (Mg²⁺ assisted, utilization of ATP for muscle contraction by ATPase)

H⁺ + ADP + CP → ATP + Creatine (Mg²⁺ assisted, catalyzed by creatine kinase, ATP is used again in the above reaction for continued muscle contraction)

2 ADP → ATP + AMP (catalyzed by adenylate kinase/myokinase when CP is depleted, ATP is again used for muscle contraction)

Muscle at rest:

ATP + Creatine → H⁺ + ADP + CP (Mg²⁺ assisted, catalyzed by creatine kinase)

ADP + P_i → ATP (during anaerobic glycolysis and oxidative phosphorylation)

When the phosphagen system has been depleted of phosphocreatine (creatine phosphate), the resulting AMP produced from the adenylate kinase (myokinase) reaction is primarily regulated by the purine nucleotide cycle.^[10]

Anaerobic glycolysis

This system is known as anaerobic glycolysis. "Glycolysis" refers to the breakdown of sugar. In this system, the breakdown of sugar supplies the necessary energy from which ATP is manufactured. When sugar is metabolized anaerobically, it is only partially broken down and one of the byproducts is lactic acid. This process creates enough energy to couple with the energy requirements to resynthesize ATP.

When H⁺ ions accumulate in the muscles causing the blood pH level to reach low levels, temporary muscle fatigue results. Another limitation of the lactic acid system that relates to its anaerobic quality is that only a few moles of ATP can be resynthesized from the breakdown of sugar. This system cannot be relied on for extended periods of time.

The lactic acid system, like the ATP-CP system, is important primarily because it provides a rapid supply of ATP energy. For example, exercises that are performed at maximum rates for between 1 and 3 minutes depend heavily upon the lactic acid system.^[1] In activities such as running 1500 meters or a mile, the lactic acid system is used predominantly for the "kick" at the end of the race.^[4]^: 11–12

Aerobic metabolism

Aerobic glycolysis

Aerobic glycolysis
Glycolysis – The first stage is known as glycolysis, which produces 2 ATP molecules, 2 reduced molecules of nicotinamide adenine dinucleotide (NADH) and 2 pyruvate molecules that move on to the next stage – the Krebs cycle. Glycolysis takes place in the cytoplasm of normal body cells, or the sarcoplasm of muscle cells.
The Krebs cycle – This is the second stage, and the products of this stage of the aerobic system are a net production of one ATP, one carbon dioxide molecule, three reduced NAD⁺ molecules, and one reduced flavin adenine dinucleotide (FAD) molecule. (The molecules of NAD⁺ and FAD mentioned here are electron carriers, and if they are reduced, they have had one or two H⁺ ions and two electrons added to them.) The metabolites are for each turn of the Krebs cycle. The Krebs cycle turns twice for each six-carbon molecule of glucose that passes through the aerobic system – as two three-carbon pyruvate molecules enter the Krebs cycle. Before pyruvate enters the Krebs cycle it must be converted to acetyl coenzyme A. During this link reaction, for each molecule of pyruvate converted to acetyl coenzyme A, a NAD⁺ is also reduced. This stage of the aerobic system takes place in the matrix of the cells' mitochondria.
Oxidative phosphorylation – The last stage of the aerobic system produces the largest yield of ATP – a total of 34 ATP molecules. It is called oxidative phosphorylation because oxygen is the final acceptor of electrons and hydrogen ions (hence oxidative) and an extra phosphate is added to ADP to form ATP (hence phosphorylation).

This stage of the aerobic system occurs on the cristae (infoldings of the membrane of the mitochondria). The reaction of each NADH in this electron transport chain provides enough energy for 3 molecules of ATP, while reaction of FADH₂ yields 2 molecules of ATP. This means that 10 total NADH molecules allow the regeneration of 30 ATP, and 2 FADH₂ molecules allow for 4 ATP molecules to be regenerated (in total 34 ATP from oxidative phosphorylation, plus 4 from the previous two stages, producing a total of 38 ATP in the aerobic system). NADH and FADH₂ are oxidized to allow the NAD⁺ and FAD to be reused in the aerobic system, while electrons and hydrogen ions are accepted by oxygen to produce water, a harmless byproduct.

Fatty acid oxidation

Triglycerides stored in adipose tissue and in other tissues, such as muscle and liver, release fatty acids and glycerol in a process known as lipolysis. Fatty acids are slower than glucose to convert into acetyl-CoA, as first it has to go through beta oxidation. It takes about 10 minutes for fatty acids to sufficiently produce ATP.^[5] Fatty acids are the primary fuel source at rest and in low to moderate intensity exercise.^[1] Though slower than glucose, its yield is much higher. One molecule of glucose produces through aerobic glycolysis a net of 30-32 ATP;^[11] whereas a fatty acid can produce through beta oxidation a net of approximately 100 ATP depending on the type of fatty acid. For example, palmitic acid can produce a net of 106 ATP.^[12]

Amino acid degradation

Normally, amino acids do not provide the bulk of fuel substrates. However, in times of glycolytic or ATP crisis, amino acids can convert into pyruvate, acetyl-CoA, and citric acid cycle intermediates.^[13] This is useful during strenuous exercise or starvation as it provides faster ATP than fatty acids; however, it comes at the expense of risking protein catabolism (such as the breakdown of muscle tissue) to maintain the free amino acid pool.^[13]

Purine nucleotide cycle

The purine nucleotide cycle is used in times of glycolytic or ATP crisis, such as strenuous exercise or starvation.^[14]^[13] It produces fumarate, a citric acid cycle intermediate, which enters the mitochondrion through the malate-aspartate shuttle, and from there produces ATP by oxidative phosphorylation.

Ketolysis

During starvation or while consuming a low-carb/ketogenic diet, the liver produces ketones. Ketones are needed as fatty acids cannot pass the blood-brain barrier, blood glucose levels are low and glycogen reserves depleted. Ketones also convert to acetyl-CoA faster than fatty acids.^[15]^[16] After the ketones convert to acetyl-CoA in a process known as ketolysis, it enters the citric acid cycle to produce ATP by oxidative phosphorylation.

The longer that the person's glycogen reserves have been depleted, the higher the blood concentration of ketones, typically due to starvation or a low carb diet (βHB 3 - 5 mM). Prolonged high-intensity aerobic exercise, such as running 20 miles, where individuals "hit the wall" can create post-exercise ketosis; however, the level of ketones produced are smaller (βHB 0.3 - 2 mM).^[17]^[18]

Ethanol metabolism

Ethanol (alcohol) is first converted into acetaldehyde, consuming NAD⁺ twice, before being converted into acetate. The acetate is then converted into acetyl-CoA. When alcohol is consumed in small quantities, the NADH/NAD⁺ ratio remains in balance enough for the acetyl-CoA to be used by the Krebs cycle for oxidative phosphorylation. However, even moderate amounts of alcohol (1-2 drinks) results in more NADH than NAD⁺, which inhibits oxidative phosphorylation.^[19]

When the NADH/NAD⁺ ratio is disrupted (far more NADH than NAD⁺), this is called pseudohypoxia. The Krebs cycle needs NAD⁺ as well as oxygen, for oxidative phosphorylation. Without sufficient NAD⁺, the impaired aerobic metabolism mimics hypoxia (insufficient oxygen), resulting in excessive use of anaerobic glycolysis and a disrupted pyruvate/lactate ratio (low pyruvate, high lactate). The conversion of pyruvate into lactate produces NAD⁺, but only enough to maintain anaerobic glycolysis. In chronic excessive alcohol consumption (alcoholism), the microsomal ethanol oxidizing system (MEOS) is used in addition to alcohol dehydrogenase.^[19]

Related Research Articles

Adenosine triphosphate (ATP) is a nucleotide that provides energy to drive and support many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of life, ATP is often referred to as the "molecular unit of currency" of intracellular energy transfer. When consumed in metabolic processes, it converts either to adenosine diphosphate (ADP) or to adenosine monophosphate (AMP). Other processes regenerate ATP. It is also a precursor to DNA and RNA, and is used as a coenzyme. A human adult processes around 50 kg of ATP daily.

The citric acid cycle—also known as the Krebs cycle, Szent-Györgyi-Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of biochemical reactions to release the energy stored in nutrients through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. The chemical energy released is available under the form of ATP. The Krebs cycle is used by organisms that respire (as opposed to organisms that ferment) to generate energy, either by anaerobic respiration or aerobic respiration. In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, that are used in numerous other reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest components of metabolism. Even though it is branded as a 'cycle', it is not necessary for metabolites to follow only one specific route; at least three alternative segments of the citric acid cycle have been recognized.

Glycolysis is the metabolic pathway that converts glucose into pyruvate and, in most organisms, occurs in the liquid part of cells. The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). Glycolysis is a sequence of ten reactions catalyzed by enzymes.

Pyruvic acid (IUPAC name: 2-oxopropanoic acid, also called acetoic acid) (CH₃COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH₃COCOO⁻, is an intermediate in several metabolic pathways throughout the cell.

Adenosine diphosphate (ADP), also known as adenosine pyrophosphate (APP), is an important organic compound in metabolism and is essential to the flow of energy in living cells. ADP consists of three important structural components: a sugar backbone attached to adenine and two phosphate groups bonded to the 5 carbon atom of ribose. The diphosphate group of ADP is attached to the 5’ carbon of the sugar backbone, while the adenine attaches to the 1’ carbon.

<span class="mw-page-title-main">Cellular respiration</span> Process to convert glucose to ATP in cells

Cellular respiration is the process by which biological fuels are oxidized in the presence of an inorganic electron acceptor, such as oxygen, to drive the bulk production of adenosine triphosphate (ATP), which contains energy. Cellular respiration may be described as a set of metabolic reactions and processes that take place in the cells of organisms to convert chemical energy from nutrients into ATP, and then release waste products.

Acetyl-CoA is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle to be oxidized for energy production.

Anaerobic glycolysis is the transformation of glucose to lactate when limited amounts of oxygen (O₂) are available. Anaerobic glycolysis is an effective means of energy production only during short, intense exercise, providing energy for a period ranging from 10 seconds to 2 minutes. This is much faster than aerobic metabolism. The anaerobic glycolysis (lactic acid) system is dominant from about 10–30 seconds during a maximal effort. It replenishes very quickly over this period and produces 2 ATP molecules per glucose molecule, or about 5% of glucose's energy potential (38 ATP molecules). The speed at which ATP is produced is about 100 times that of oxidative phosphorylation.

Digestion is the breakdown of carbohydrates to yield an energy-rich compound called ATP. The production of ATP is achieved through the oxidation of glucose molecules. In oxidation, the electrons are stripped from a glucose molecule to reduce NAD+ and FAD. NAD+ and FAD possess a high energy potential to drive the production of ATP in the electron transport chain. ATP production occurs in the mitochondria of the cell. There are two methods of producing ATP: aerobic and anaerobic. In aerobic respiration, oxygen is required. Using oxygen increases ATP production from 4 ATP molecules to about 30 ATP molecules. In anaerobic respiration, oxygen is not required. When oxygen is absent, the generation of ATP continues through fermentation. There are two types of fermentation: alcohol fermentation and lactic acid fermentation.

Carbohydrate metabolism is the whole of the biochemical processes responsible for the metabolic formation, breakdown, and interconversion of carbohydrates in living organisms.

The term amphibolic is used to describe a biochemical pathway that involves both catabolism and anabolism. Catabolism is a degradative phase of metabolism in which large molecules are converted into smaller and simpler molecules, which involves two types of reactions. First, hydrolysis reactions, in which catabolism is the breaking apart of molecules into smaller molecules to release energy. Examples of catabolic reactions are digestion and cellular respiration, where sugars and fats are broken down for energy. Breaking down a protein into amino acids, or a triglyceride into fatty acids, or a disaccharide into monosaccharides are all hydrolysis or catabolic reactions. Second, oxidation reactions involve the removal of hydrogens and electrons from an organic molecule. Anabolism is the biosynthesis phase of metabolism in which smaller simple precursors are converted to large and complex molecules of the cell. Anabolism has two classes of reactions. The first are dehydration synthesis reactions; these involve the joining of smaller molecules together to form larger, more complex molecules. These include the formation of carbohydrates, proteins, lipids and nucleic acids. The second are reduction reactions, in which hydrogens and electrons are added to a molecule. Whenever that is done, molecules gain energy.

Anaerobic exercise is a type of exercise that breaks down glucose in the body without using oxygen; anaerobic means "without oxygen". In practical terms, this means that anaerobic exercise is more intense, but shorter in duration than aerobic exercise.

Fatty acid metabolism consists of various metabolic processes involving or closely related to fatty acids, a family of molecules classified within the lipid macronutrient category. These processes can mainly be divided into (1) catabolic processes that generate energy and (2) anabolic processes where they serve as building blocks for other compounds.

The Cori cycle, named after its discoverers, Carl Ferdinand Cori and Gerty Cori, is a metabolic pathway in which lactate, produced by anaerobic glycolysis in muscles, is transported to the liver and converted to glucose, which then returns to the muscles and is cyclically metabolized back to lactate.

Substrate-level phosphorylation is a metabolism reaction that results in the production of ATP or GTP supported by the energy released from another high-energy bond that leads to phosphorylation of ADP or GDP to ATP or GTP (note that the reaction catalyzed by creatine kinase is not considered as "substrate-level phosphorylation"). This process uses some of the released chemical energy, the Gibbs free energy, to transfer a phosphoryl (PO₃) group to ADP or GDP. Occurs in glycolysis and in the citric acid cycle.

The Pasteur effect describes how available oxygen inhibits ethanol fermentation, driving yeast to switch toward aerobic respiration for increased generation of the energy carrier adenosine triphosphate (ATP). More generally, in the medical literature, the Pasteur effect refers to how the cellular presence of oxygen causes in cells a decrease in the rate of glycolysis and also a suppression of lactate accumulation. The effect occurs in animal tissues, as well as in microorganisms belonging to the fungal kingdom.

The lactate shuttle hypothesis describes the movement of lactate intracellularly and intercellularly. The hypothesis is based on the observation that lactate is formed and utilized continuously in diverse cells under both anaerobic and aerobic conditions. Further, lactate produced at sites with high rates of glycolysis and glycogenolysis can be shuttled to adjacent or remote sites including heart or skeletal muscles where the lactate can be used as a gluconeogenic precursor or substrate for oxidation. The hypothesis was proposed by professor George Brooks of the University of California at Berkeley.

Pseudohypoxia refers to a condition that mimics hypoxia, by having sufficient oxygen yet impaired mitochondrial respiration due to a deficiency of necessary co-enzymes, such as NAD⁺ and TPP. The increased cytosolic ratio of free NADH/NAD⁺ in cells (more NADH than NAD⁺) can be caused by diabetic hyperglycemia and by excessive alcohol consumption. Low levels of TPP results from thiamine deficiency.

Pyruvate decarboxylation or pyruvate oxidation, also known as the link reaction, is the conversion of pyruvate into acetyl-CoA by the enzyme complex pyruvate dehydrogenase complex.

<span class="mw-page-title-main">Citrate–malate shuttle</span>

The citrate-malate shuttle is a series of chemical reactions, commonly referred to as a biochemical cycle or system, that transports acetyl-CoA in the mitochondrial matrix across the inner and outer mitochondrial membranes for fatty acid synthesis. Mitochondria are enclosed in a double membrane. As the inner mitochondrial membrane is impermeable to acetyl-CoA, the shuttle system is essential to fatty acid synthesis in the cytosol. It plays an important role in the generation of lipids in the liver.

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