• 14 JAN 14
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    Whole Body Metabolism & Micronutrition 101

    Whole Body Metabolism & Micronutrition 101

    Diet and nutrition is often seen as a contentious subject. The topic is filled with polarised opinions and confusion, often fabricated by over zealous ‘clinical’ nutritionists relying on anecdotal observation or limited clinical evidence at best. The pseudoscientific journalists writing in magazines or online media sponsored by industry giants, trying to sell more advertising space have stirred the pot well. But does everyone involved have a vested financial interested? As an idealist I like to think not, I believe there are people who do actually care and actively share good information because they want to be seen as altruistic pioneers of new paradigms and technology while others use this confusion to their advantage creating an air of mis-trust. You may agree that scientists in general are a strange breed, they see the world as how it could or should be, always challenging themselves to solve problems and answer questions, which usually involves a personal sacrifice whether they are aware of that or not, think the Curies. True invention and innovation rarely escape commercialisation (even if the inventor doesn’t make any money), however this usually requires less promotion than the copycats trying to sell ‘improved’ versions with ever more complicated patents. For many of the scientists I have known, leaving their legacy in print for the future generations on this planet to admire, really is their Holy Grail! There are exceptions to the rule, naturally. The ‘environmental mutations’ I like to call them. Combining commercial success and innovation is an art form in the modern world, and frequently impressive.

    It is difficult to pick the good guys from the bad…but when a billion pound industry is at stake I feel anything is possible. Call me a skeptic if you must…..then we can move on to the reality about whole body metabolism and nutrition.

    Atkins, Zone, Learn, Ornish, Paleo all have rational biochemical theory behind them, favouring micronutrient dense foods in different proportions disputing and discrediting one anothers methods even down to % ratio carbs:protein:fat. But surely you can have the best of both worlds? Which makes total sense, train low- /race hi- carb eating principle has long been an obvious philosophy for extreme endurance athletes, especially marathon runners. These so called ‘revelationary’ ideas are thrust onto the front line in a cyclical manner to only to be undermined by the next ‘school of thought’. The understanding of the science is often diluted to such a great extent even the researchers get lost in their own focus. The problem with the proposals is that they treat everyone as having exactly the same typical physiology and they certainly don’t take into account the dietary requirements of endurance athletes. Our metabolism may function in a similar way, but the controls may be different for everyone.


    We can think of exercising as the same as fasting but with one important difference, the increase in the circulating glucose products (pyruvate and lactate) resulting from enhanced glucose metabolism (glycolysis). Otherwise the pattern of change in plasma substrates is similar to that of fasting, only telescoped in time. Many of these diets do not account for an increased requirement for essential amino acids or total protein, not just for muscle tissue turnover, but immune system function and many other processes in the body.

    Over the last couple of years when I was in Italy, I got wind of Dr.Lemme and his dieting advice, has he been quite controversial? Dr. Lemme suggests, usually by poking his finger at vertically challenged people (good selection bias there) that to lose weight you should eat natural foods until full three times a day only, thats it. I’m probably missing something here, but the rationale behind this approach seems disturbingly normal. Have we deviated from common sense so much that people have forgotten? Does he suggest calling those three meals breakfast, lunch and dinner by any chance of the imagination!? Why is this controversial? If the body is deprived of nutrition it hordes what it can for a later date or if it does not receive the right type of nutrients then it is unable to process the substrates properly and enters a sub-optimal state. Dr. Lemme relies on simple biochemistry that energy substrates aren’t stored to excess if they are available to the body on a frequent basis (as there are plenty of negative feed back loops to prevent storage and the body excretes what it doesn’t need).

    Reliance on the thermogenic effect of food (Dietary Induced Thermogenesis, DIT) is seen as an exploitable part of diets. It is, but you need to be very strict to use DIT it in your favour on a long term basis. This doesnt mean that optimal nutrition is necessarily complex, as simple principles maybe applied in a combination of ways. The problem lies with the different phenotype between individuals (the natural physiological variation; sympathetic nervous activity, basal metabolic rate, homeostasis and endocrinology which controls calorific control when at rest or asleep, and response to food intake, degree of absorption, excretion and instant metabolism of carbohydrate, fat and protein substrates). Much of the energy we expend is used by the brain alone, maybe more than 60% of daily energy. Then you would think the muscles use the next largest proportion, when in fact the blood and cellular ion pumps which regulate the distribution of Potassium, Sodium and Calcium need so much ATP (the molecule required for energy transfer) to create electrical activity in the cells before contraction even occurs in cardiac, smooth or skeletal muscle. So much in fact, that the ‘typical’ total amount (128 moles) of ATP produced by your body in one day, would weigh 68kg, a value approaching body weight!

    Science has been my passion as long as I have been cycling and running, I’m not sure which one came first even. We all interact with nature and are fascinated by our existence, and for me it was easy to make it my direction in life, to understand how we can disease proof ourselves and improve our existence.  We are our own unique experiments (n=1), although I don’t advocate extreme self-experimentation as clearly this could be detrimental to health, we unwittingly expose ourselves to numerous chemical and physical stimuli every day. Our own unique physiology can never be replicated by that of a clinical trial capturing mean data and applying it to a ‘typical’ person. Results need to be generalisable (or personalisable) and pragmatic. N=1 is a valid experiment as long as you only generalise your findings to yourself, diet and nutrition is as personal as training, BUT they follow very specific rules if you are to achieve optimal functioning, especially in athletic individuals who strive for top performances on regular occasions.

    My background in nutritional science was initially formed by lectures (among a few others) in the biochemistry of metabolism and Krebs cycle when Prof Jack Salway at Surrey University was still debating the number of ATP produced by 1 molecule of glucose, as well as by the regurgitation of lectures in nutrition by my girlfriend at the time, folic acid this, niacin that….I’m glad I was a good listener. Exciting stuff I here you say! You’re right, it probably wasn’t, but perpetual questioning of research conclusions until overwhelming evidence is established is more or less the fastest way to scientific progression and advances have been stifled unnecessarily because of this. Otherwise a result is taken at face value and subsequent research can easily take the wrong path and lessen the chances of serendipity. A good trait of a researcher is the ability to appraise both positive and negative, and put the result in context of all other research performed to date.  As Thomas Edison holder of over a 1000 US patents said, “I have not failed. I have just found 10,000 ways that won’t work.” There have been few great discoveries since commercial and academic research have been subjected to systematic regulation and financial control mechanisms. This is exactly the point where my cynicism comes into play. Prevention is key.  No longer can we rely on researchers and physicians to provide us with adequate healthcare, as the gap between demand and supply is continuously growing, and fewer doctors are there to pick up the pieces. Nutraceuticals are fast becoming the new pharmaceuticals. In the nutrient depleted athlete, supplements are an acceptable way to restore balance. It is only when these products are sold as extraordinary ergogenic aids that athletes should remain cautious of their integrity.

    Health conscientious folk need complete and perfect information to disease proof themselves (nutrition and dietetics plays a massive role in the development of many cancers, cardiovascular disease and metabolic diseases such as diabetes and obesity), yet are still being duped. Common myths about diet have not been debunked, as fast-food still thrives and obesity continues to rise. Although there will always be a fraction of the population impervious to common sense I hear you say. However, I believe most people who read this post understand why common sugar (sucrose) should be perceived as a potentially toxic compound. Social conditioning over centuries has made us believe that sugar added to food should be tolerated. In a similar way that alcohol and smoking has been previously tolerated and still is to great extent?

    Trans-fats and saturated fats being ‘evil’ perpetrators of cardiovascular disease, as per the six-nation study conducted in the 1970’s which has now, 40 years later, only just been questioned! Grey areas and sliding scales naturally exist in science, but also do hard unchallenged facts which form the backbone of much taught material, you have to be an extreme cynic to question these tenets of science. Imagine if Watson and Cricks discovery of the DNA double helix, was wrong? Metabolic syndrome and how insulin resistance is caused through high sugar/fat diets? Can the science behind essential Poly Unsaturated Fatty Acids (PUFAs) really highlight the importance of the Omega 3:6 ratio, and DHA/EPA and ALA necessary as part of essential fatty acids? How much protein and from which source? The role of cholesterol and LDL/HDL levels and statins the commercial endpoint of successful disease mongering? Low carbohydrate diets? Low carb/ high fat ‘ketogenic’ diets? Is there too much conflict or confusion?

    Many unanswered questions are floating around still and rightly so, although a few credible figures have published elegant reviews of the current stance on the understanding of whole body metabolism and its application to sports nutrition. I leave it up to you to judge the effects they may have on yourself, but to understand their relevance to your unique physiology, the principles behind them need to be put in scientific context. I hope I can help you do that by at least 1% more by providing you with sound information I have assimilated within this post. My aim, purely, is to provide you with the tools to understand your own physiology a little bit better, and how metabolically flexible and adaptable the human body can be.



    At rest (ie. measured just after waking) it can be said that approximately 70% of expended calories come from the oxidation of fats and 30% from carbohydrate stored as glycogen in the muscle and liver. Energy is expended in a myriad of synthetic and degradative chemical reactions, in generating and maintaining gradients of ions and other molecules across cell and organelle membranes, creating and conducting electrical signals, particularly in the nervous system, and in the mechanical work of respiration and circulation of the blood. The brain and red blood cells rely predominantly on glucose broken down from this glycogen which only lasts for about three hours (the pool of glucose is only slightly larger than the output from the liver).  After which  ketone bodies and lactate are become fuels. All of these processes require an intake of oxygen along with coenzymes to provide energy for survival (usually from macronutrients like carbohydrates, fats, and proteins) and expel carbon dioxide, due to processing by the Krebs cycle. The basal metabolic rate is the absolute minimal energy expenditure which dictates the total number of calories used by either fat or carbohydrate metabolism at rest. In the adult human BMR amounts to an average daily expenditure of between 20 to  25 KCal/kg body weight and requires the utilisation of approximately 200 to 250 ml oxygen/minute. 

    BMR is increased by raising environmental temperature which means you are processing more calories for ion regulation but will require fewer calories to sustain greater levels of activity probably due to improved efficiency with temperature. During sleep BMR falls by 10 to 15%. Studies in identical twins and families suggest that some of the variation in BMR is genetically determined. There has been a lot of uncertainty about the relationship of BMR and lean muscle mass, but it seems clearer now that even though more lean mass may not increase BMR significantly, the degree of metabolically active muscle and some unexplained genetic differences will determine the differences of BMR in individuals of similar lean mass. A difference in BMR maybe as much as 700kCal for individuals of the same percentage lean mass. Although this declines with age, partly because lean body mass declines due to inactivity and sedentary lifestyles.



    About 75% of the average total daily energy expenditure in a sedentary human accounts for basal metabolism as explained above. A further 7% can be explained by dietary induced thermogenesis (DIT) or postprandial thermogenesis. Facultative thermogenesis is related to production of body heat when exposed to cold, but not due to shivering or spontaneous activity. Ingestion of food causes a small increase in energy expenditure referred to as dietary induced thermogenesis. The thermic effect of food is the energy required for digestion, absorption, and disposal of ingested nutrients and is a result of the increased rate of reactions involved in the disposition of the ingested calories, such as storage of glucose in the large molecule glycogen and anabolic production of proteins in muscle tissue.  Its magnitude depends on the composition of the food consumed. Different nutritional substrates account for  varying percentages of calorie expenditure after food intake, with differing values dependent on the substrate of fuel; carbohydrate, fat or protein. Protein has the highest thermogenic action of all three, accounting for almost 35% of expended calories after ingestion of a protein based meal.  For example, dietary fat is very easy to process and has very little thermic effect, while protein is hard to process and has a much larger thermic effect.

    • Carbohydrates: 5 to 15% of its own energy consumed
    • Protein: 20 to 35%
    • Fats: at most 5 to 15 %

    Certain foods are known to have a positive influence on DIT for a variety of reasons, from negative calorific balance (requiring more energy to digest, than is recovered from the food) or the sensitivity of an individual to insulin.While individuals with increasing insulin-resistance as in metabolic syndrome or type II diabetes have little to no effect for DIT. Caffeine and EGCG found in Green tea are thought to increase thermogenesis through the sympathetic nervous systems via the catecholamines and epinephrine. Body building  supplements commonly marketed as thermogenic products ‘fat burners’ containing these active ingredients have entered the main stream dieting industry. These are considered natural fat-burners along with L-Carnitine a protein which chaperones fatty acids and makes them more available for metabolism.  Even better news is the current research on Capsaicin, the active component found in chilli peppers frequently used in curries. A recent study has shown that Capsaicin when combined with medium-chain triglycerides (MCT) increases diet-induced thermogenesis, improves satiety and decreases energy intake. Further, research has found that the thermic effect of food contributes to the fact that calories may not all be equal in terms of weight gain as similar calorific content, processed food vs whole foods result in  greater energy availability after digestion and absorption. Even more good news is that the thermic effect of food is increased by both aerobic endurance training and by anaerobic weight training, which positively effects levels of metabolically active lean mass and therefore BMR.


    The fasting individual is said to be in a state of catabolism because carbohydrate, fat and protein stores are all decreasing. Glucose oxidation in muscle and liver is spared as increasing quantities of free fatty acids become available. The net shift away from glucose and toward fatty acid oxidation lowers the respiratory quotient. The concentrations of glucose and the major gluconeogenic amino acid Alanine decrease, whereas the concentrations of free fatty acids, glycerol and BCAA such as Leucine increase.

    As fasting is prolonged beyond a few days, other important adaptations occur. Total energy expenditure, reflected in the BMR, decreases 10-20% limiting the drain on energy stores. The central nervous system no longer depends entirely on glucose as an energy source and two thirds of its needs are eventually met by the ketoacids.

    In long term fasting body weight diminishes by an average of 300g/day of which two thirds is accounted for by fat and one third by lean tissue of which 25% constitutes protein and 75% intra-cellular water and electrolytes. Of the latter, 25% constitutes protein and 75% intra-cellular water and electrolytes. In long term-term fasting fatty acids provide 90% of the total energy expenditure. About the times fat stores are almost exhausted, protein degradation suddenly accelerates.

    To prevent this glucose reserve from running out, protein amino acids (alanine) and lactate can be reverse-metabolised to glucose through a process called gluconeogenesis and through alanine which is glucogenic, can be metabolised to glucose in the liver) . This pathway relies on fatty acid metabolism to supply energy for the re-conversion. Glucose oxidation in the liver and muscle is spared as increasing quantities of free fatty acids become available.  A portion of fatty acid oxidation yields the keto-acids; B-hydroxybutyrate, acetoacetate and other minor ketoacids, termed ketone bodies, produced by incomplete triglyceride metabolism.

    Fat being the predominant storage form of triglycerides, cannot be converted back to glucose and only enters Beta-oxidation in the muscles or in the liver, and also to B-hydroxybuturate (a ketone molecule which has a similar sub-structure to glucose) which can be used by the brain and blood. Therefore at rest fat metabolism is favoured as to preserve glucose stores and prevent muscles/ tissues from wasting. This can be seen in the resting respiratory quotient or RER (ratio of oxygen inhaled to carbon dioxide exhaled which is lowered).


    Hormone control- Insulin and Glucagon

    When an individual ingests glucose after overnight fasting, approximately 70% of the load is assimilated by peripheral tissues, mainly muscle and about 30% by the liver.

    In liver, glucose availability reinforces those effects of insulin that lead to toward glycogen storage or glycolysis and away from glucose release. The most important effect of insulin in adipose tissue is to stimulate production of alpha-glycerol phosphate from the intermediates of glucose metabolism. This is used to esterify free fatty acids, thus storing them as triglycerides. 70% of glucose isn’t controlled by insulin under conditions of the basal metabolic rate. Secreted or administered insulin decreases the plasma concentrations of glucose, of free fatty acids and ketoacids, and of predominantly the essential branched-chain amino acids (leucine, isoleucine and valine). The major sites of insulin action are the liver, muscle and adipose tissue. Most of the extra glucose uptake occurs in the muscle, with a very small fraction in adipose tissue.

    Under the control of insulin, free fatty acids are converted to triglycerides and stored in adipose tissue when glucose is abundant.The basal rate of free fatty acid inflow to plasma- equivalent to the rate of release from adipose tissue- is decreased by two-thirds by insulin. As a result of this reduction in free fatty acid availability, insulin reduces the basal rate of lipid oxidation more than 90%. Lipids and their products contribute little directly to the insulin response to a meal. Taken together with the fact that the presence of free fatty acids in the circulation suppresses the storage of these fats in adipose tissue.

    The low insulin concentrations that prevail in the overnight fasting state are partly able to restrain and thereby regulate endogenous release of free fatty acids and amino acids. The peak insulin concentrations elicited by a meal greatly stimulate glucose and amino acid uptake by peripheral tissues, especially muscle. The key metabolic role of insulin means that its absence causes a dramatic distortion of homeostasis. Plasma levels of glucose, free fatty acids, and ketoacids rise to extreme heights. This causes plasma pH and bicarbonate to fall. Extreme loss of adipose mass and lean body mass occurs.

     Substrate fluxes are very sensitive to the relative availability of insulin and glucagon. The usual molar a ratio of insulin to glucagon in plasma is about 2.0. Under conditions of fasting or prolonged exercise this ratio drops to around 0.5 as there is both a decrease in insulin and increase in glucagon secretion.

    After a pure carbohydrate load or mixed meal, this ratio rises to 10 or more, mainly because of increased insulin secretion. However after ingesting a pure protein meal, interestingly there is only a small and insignificant change in the insulin/ glucagon ratio. In this situation insulin secretion increases facilitating muscle uptake and there synthesis into proteins. At the same time glucagon also increases. This prevents the immediate decrease in hepatic glucose output and hypoglycaemia that would ensue if the extra insulin action were unopposed. Insulin may act directly to increase satiety signals and dampen hunger when plasma glucose is elevated. However when glucose levels drop below those needed for normal brain metabolism (less than 50g/dl) hunger is stimulated, even if the hypoglycemia was induced by insulin administration.

    As glucose levels are lowered the effects of insulin become attenuated by the secretion of hormones (glucagon, epinephrine, cortisol, growth hormone) with actions antagonistic to insulin.

    You can read more about fructose, high levels of triglycerides and the causes of insulin resistance here.


    Glucagon is an important hormonal regulator of intrahepatic glucose and free fatty acid metabolism, and its release is stimulated (in contrast to insulin) by low glucose levels. Amino acids stimulate glucagon secretion, and glucagon in turn stimulates amino acids conversion to glucose. Free fatty acids also suppress glucagon release. The glucagon response to a protein meal and amino acids, a substrate for glucose production, stimulates glucagon secretion but this response is dampened by concurrent glucose or insulin action through negative feedback loops. As a result the usual mixed meal produces only a small and variable increase in plasma glucagon levels, in contrast to the large and consistent increases in plasma insulin levels. Glucagon maybe the primary hormone that regulates hepatic glucose production (and ketogenesis) with insulin’s main role being that of a glucagon antagonist. Glucagon suppresses glycolysis and promotes gluconeogenesis and increasing hepatic glucose output. The action of glucagon is also to direct incoming free faty acids away from triglyceride synthesis and toward B-oxidation. Thus glucagon is a ketogenic hormone.


    Maximal doses of insulin decrease the rate of inflow of leucine into plasma by almost half. Because the only source of leucine in the basal state is endogenous protein, this action of insulin must be caused by inhibition of proteolysis (muscle breakdown). In addition, insulin decreases the rate of oxidation of leucine. The result of these insulin effects is a net gain in body protein (muscle, cartilage and osseous tissue) and has an important contribution to anabolic growth, tissue regeneration, and to bone remodelling.

    All proteins are composed of the same 20 amino acids. Half of these are call essential amino acids because their carbon skeletons, the corresponding alpha-ketoacids, cannot be synthesised by humans and must be supplied in the diet. All 20 amino acids are required for normal protein synthesis, therefore a deficiency of even one essential amino acid disrupts this process. In addition to their incorporation into proteins, many of the amino acids, including some essential ones, are precursors for important molecules, such as those involved in DNA/RNA synthesis; purines, pyrimidines, polyamines, phospholipids, creatine, carnitine, thyroid and catecholamine hormones, and neurotransmitters

    Digestion of protein in a meal yields amino acids, some of which synergise with glucose in stimulating the release of insulin. Which decreases the concentration of the essential branched chain amino acids, leucine, isoleucine and valine as a protective effect and ultimately building up storage in lean muscle mass. Protein constitutes almost 25% of the potential energy reserves, and the component amino acids can contribute to the glucose supply. However, virtually all proteins serve some vital structural and functional role. Therefore their use as a major source of energy is deleterious and only arises as a last resort. Protein can be converted to glucose easily (all glucogenic amino acids except for leucine). This means that excess protein can be processed to fat stores in an abundant presence of glucose or glycogen stores, via acetyl-CoA or malonyl-CoA. Therefore sufficient protein intake will preserve muscle degradation and inhibit mobilisation of glucose from glycogen stores, and thus preserve these precious stores of glucose for brain/ blood and muscle function.

    As the brain neurons and blood cells are only able to utilise glucose, continuous hepatic production of glucose is critical during the fasting state. So, all resources are directed to maintaining this pool, including using protein from muscle degradation in the form of the alanine- glucose cycle which particularly occurs during exercise. Healthy adults who receive balance calorie diets of 0.5 – 1.5g/kg/ day protein (minimal for resting metabolic rate) complete with the essential amino acids and who are in nitrogen balance, synthesise and degrade body protein at a rate of 3 to 4g/kg/day. These values can be significantly higher in individual who undertake heavy exercise, requiring maybe as much as 1.4-1.8g/kg/day. 23% of the energy from the original calories is expended in storing dietary amino acids as protein or in converting them to glycogen.

    Protein sources vary greatly in their biological effectiveness, depending in part on the ratio of essential to non-essential amino acids and their digestibility (see review). Milk and egg proteins are the highest quality in this respect. A score has been assigned to rank food based on the Protein Digestibility Corrected for the Amino Acids (PDCAA). Although the proportion of essential to non-essential amino acids would be more helpful to understand. When the diet is severely deficient in energy, total protein, or one of the essential amino acids, the rate of total body protein synthesis diminishes. In compensation, protein degradation also diminishes, but not to the same extent as synthesis, so that net loss of body protein results.


    During the period of peak absorption of exogenous glucose, hepatic output of the sugar is largely unnecessary and is greatly reduced from basal levels. Approx 25% glycogen is stored in the liver, and 75% in the muscle mass. Liver glycogen can be made available to other tissues whereas muscle glycogen lacking a certain enzyme cannot.

    When dietary glucose is plentiful, glycolysis is increased (the production of energy from glucose) although not necessarily aerobically to produce citrate, a potent activator in the first step of fatty acid synthesis. This produces more glycerol and promotes fatty acid synthesis, but suppresses oxidation of fat. Thus increased carbohydrate utilisation shifts fat metabolism from oxidation to storage.

    This is also regulated by hormonal control, although 70% of glucose is independent of the action of insulin under resting metabolic rate conditions. When the plasma glucose level falls below 60mg/dl, brain uptake of the sugar and brain utilisation of oxygen decrease in parallel. Central nervous system function becomes progressively impaired. Brain accounts for the highest proportion of glucose oxidation at the BMR. The glucose pool in the body is only slightly larger than the total liver output in 1 hour, and is only sufficient to maintain brain oxidation for 3 hrs even if all other glucose utilisation ceased. This emphasises the crucial importance of continuous hepatic production of glucose in the fasting state. Hepatic uptake and utilisation of circulating lactate accounts for more than half the glucose supplied by gluconeogenesis. The remainder is largely accounted for by amino acids namely alanine. The supply of lactate comes from glycolysis in muscle, red blood cells, white blood cells, and a few other tissues. The amino acid precursors come from proteolysis of muscle.

    Carbohydrate in the form of the glucose polymer, glycogen, forms less than 1% of total energy reserves. This portion is critical for support of central nervous system metabolism and for short bursts of intense muscle work. The cost of storing glucose as glycogen is only 7% of the original calories. However conversion of carbohydrate to fat uses up 23% of the original calories.

    Interconversion of energy between triglycerides and free fatty acids (adipose fat tissue) and glucose in the liver/muscle- Glucose/Lactate Cori cycle. The stored energy contained within adipose tissue triglycerides is transported as free fatty acids to the liver. There, part of the energy is effectively transferred to glucose molecules, because as fatty acids are oxidised, gluconeogenesis (formation of glucose from lactate or amino acid ketone bodies) is stimulated concurrently. The newly synthesised  glucose molecules in turn can then be transported to muscle tissue, where the energy is released during glycolysis and applied to muscle contraction. If the lactate produced exceeds the ability of the muscle to oxidise it rapidly enough in the citric acid cycle, the lactate can be returned to the liver, where it maybe built back up into glucose molecules, and stored as glycogen in that organ.

    The combustion of carbohydrates, chiefly glucose with lesser amounts of fructose and galactose, include two major phases:

    At the end of an anaerobic phase known as glycolysis, each glucose molecule has yielded two molecules of pyruvate but only 8% of its energy content. Glycolysis can only serve as a sole source of energy only briefly because the supply of glucose is limited, and  because the accumulated pyruvate must be syphoned off by reduction to lactate.

    The aerobic phase, pyruvate enters Krebs cycle and the remaining energy is liberated.


    Fat is the major and most advantageous form of stored fuel. The major component of both dietary and storage fat is triglycerides. These largely consist of long-chain saturated and mono-unsaturated fatty acids esterified to glycerol. As these can be synthesised in the liver and adipose tissue, there is no strict dietary requirement for them. However, about 3-5% of fatty acids are polyunsaturated and cannot be synthesised in the body (linoleic or linolenic) because they are required as precursors for certain phospholipid and glycolipid substances, as well as important intracellular mediators known as prostaglandins and eicosanoids. Another component of fat is the steroid molecule cholesterol which serves as a precursor for bile acids and steroid hormones.

    Triglycerides are formed by esterification of free fatty acids, largely derived of the diet, with alpha-glycerol phosphate from Triose Phosphate metabolism.

    However, free fatty acids can also be synthesised from acetyl CoA derived from oxidation of glucose; thus carbohydrate can be converted to fat in liver and adipose tissue and its energy stored in that more efficient form.

    Dietary fat can contain mono, poly unsat and saturated, trans fat.

    LDLs (Low Density Lipoproteins) are responsible for transferring cholesterol into other cells. Cholesterol uptake also suppresses its own synthesis. HDLs (High Density Lipoproteins) regulate the other lipoproteins. The net effect of HDL is to accelerate clearance of triglycerides from plasma and regulate the ratios of free to esterified cholesterol.

    The plasma concentration of total cholesterol and especially of LDL cholesterol is a very important risk factor for atherosclerosis and death from cardiovascular events. HDL cholesterol exerts a protective effect against cardiovascular disease.

    Fat metabolism

    Insulin facilitates transfer of circulating fat into the adipose cell by increasing the enzyme lipoprotein lipase. Thus dietary fat not needed for immediate energy generation is stored. Of equal or greater importance, insulin profoundly inhibits the reverse reaction (lipolysis of stored triglyceride) by decreasing the necessary enzyme, hormone-sensitive adipose tissue lipase. Free fatty acid is released and delivery to other tissues is greatly suppressed.

    In the liver, insulin promotes fatty acid synthesis and esterification and storage of triglycerides, and reduces fatty acid oxidation. Thus insulin is anti-ketogenic, and the net effect is to increase the fat content of the liver.

    Limited entry points or convergence into glucose metabolism for net formation from acetyl –CoA or other glucogenic substrates. Net glucose synthesis cannot occur from acetyl CoA. Thus fat can only contribute to carbohydrate stores by way of the 3 carbon glycerol moiety of triglycerides, a minor source.

    75% of energy reserves are in the form of fat as triglycerides stored in adipose tissue. Fat stores can supply energy needs for up to 2 months in totally fasted individuals of normal weight.

    Combustion (conversion into ATP and FADH/NADH forms of energy) of fatty acids proceeds through a repetitive biochemical process called Beta-oxidation in both the muscles and the liver.



    The oxidative system (aerobic) is the primary source of ATP supplied to the body at rest and during low intensity activities, and uses primarily carbohydrates and fats as substrates. Protein is not normally metabolized to a great extent, except during long term starvation and long bouts of exercise (greater than 90 minutes.) At rest approximately 70% of the ATP produced is derived from fats and 30% from carbohydrates. Following the onset of activity, as the intensity of the exercise increases, there is a shift in substrate preference from fats to carbohydrates. During high intensity aerobic exercise, almost 100% of the energy is derived from carbohydrates, if an adequate supply is available. The body can blend the three macronutrients (fat, carbohydrate and protein) and based on the mitochondrial density, a preferred ratio can be established which determines how much fuel is utilized in which packets for work accomplished by the muscles. Protein catabolism (breakdown) has been estimated to supply 10% to 15% of the total energy requirement during a two-hour aerobic training session. This process could severely degrade the protein structures needed to maintain survival such as contractile properties of proteins in the heart, cellular mitochondria, myoglobin storage, and metabolic enzymes within muscles.

    The metabolic response to exercising resembles the response to fasting , in that the mobilisation and generation of fuels for oxidation are dominant factors. The type and amounts of substrate vary with the intensity and duration of the exercise. For very intense, short-term exercise (eg a 30-60 second sprint, stored creatine phosphate and ATP provide the energy at a rate of approximately 50kcal/min. When these stores are depleted, additional intensive exercise for up to 2 minutes can be sustained by breakdown of muscle glycogen to glucose-6-phosphate, with glycolysis yielding the necessary energy. This anaerobic phase is not limited by depletion of muscle glycogen at this point, but rather by the accumulation of lactate and drop in pH (rise in acidity) in the exercising muscles and the circulation.

    After several minutes of exhaustive anaerobic exercise, an oxygen debt of 10 to 12L can be built up, Excess Post-exercise Oxygen Consumption (EPOC). This must be repaid before the exercise can be repeated.

    From 6 to 8L are required either to rebuild the accumulated lactic acid back into glucose in the liver or oxidise it to CO2, About 2L are required to replenish normal muscle ATP and creatine phosphate content. A further 2L will replenish the oxygen present in the lungs and body fluids and oxygen bound to myoglobin and haemoglobin.

    For less intense but longer periods of exercise, aerobic oxidation of substrates is required to produce the necessary energy. Substrates from the circulation are added to muscle glycogen. Glucose uptake increases dramatically. To offset this drain, and provide glucose for the brain and blood cells, hepatic glucose production increases up to 5 fold. Once glycogen stores are depleted, glucose levels are sustained from a reverse process called gluconeogenesis which which relies on circulating lactate from enhanced glycolysis (anaerobic) or alanine and other amino acids released by muscle proteolysis. Eventually, fatty acids, liberated from adipose tissue triglyceride, form the predominant substrate, supplying two thirds of the energy needs during sustained exercise.



    Congratulations if you made this far, still awake! Sitting through lectures on physiology and nutrition are a lot harder. Thats why, after trawling You Tube, I have posted the video link below of this animated fitness practitioner in the US. I believe he provides an excellent rendition and summary of the mechanisms behind achieving a stable and robust metabolism incorporating fat loss (without too much boring sciency biochemistry) and how these may be exploited, a key step towards improving power-to-weight in any endurance sport. Here’s also a decent list of low-carb foods to get you motivated and firing-up that fat burning metabolic furnace!




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