Carbohydrate metabolism in muscle -
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Download PDF. Abstract Purpose Carbohydrates CHO are one of the fundamental energy sources during prolonged steady state and intermittent exercise.
Methods Narrative review. Results A number of potential barriers were identified, including gastric emptying, intestinal absorption, blood flow splanchnic and muscle , muscle uptake and oxidation. Conclusion We highlight a number of potential barriers involved with the regulation of both ingested and infused CHO during exercise.
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Introduction Carbohydrates CHO and fats are the two major energy sources that fuel muscle during prolonged steady state and intermittent exercise. Full size image. Insulin and exercise stimulated GLUT4 translocation to the cell membrane in skeletal muscle.
Hormonal response to CHO ingestion and infusion during exercise The complexity and diversity of the entire hormonal response to exercise are too large to be covered in detail here, and so the focus on the metabolic effects of exercise in relation with the endocrine response will be confined to insulin, glucagon, and the sympathoadrenal system.
Oxidation of ingested sources of CHO: dose and type of CHO The progression from CHO ingestion to its oxidation and use as an energy source is a complex process, one which Rosset et al. Oxidation and utilisation of infused glucose The hyperglycaemic glucose clamp technique was devised by DeFronzo et al.
Muscle glucose oxidation during exercise Muscle glycogen is the predominant CHO source during moderate to intense exercise, and the rate of degradation is related to the relative exercise intensity.
Conclusion Ingested CHO sources are not oxidised by skeletal muscle in the same proportion as they are ingested. References Ahlborg G, Felig F Influence of glucose ingestion on fuel-hormone response during prolonged exercise.
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Metabolic and respiratory parameters were measured during the exercise. The respiratory exchange ratio, blood lactate, blood pyruvate, blood glucose and plasma triglycerides were lower than normal following the low CHO diet and higher than normal following the high CHO diet.
Plasma free fatty acids and plasma glycerol were higher than normal after the low CHO diet and lower than normal after the high CHO diet. The contribution of CHO to metabolism was less than normal after the low CHO diet and greater than normal after the high CHO diet.
The altered availability of FFA does not appear to be a result of the variations in the blood lactate content. This is a preview of subscription content, log in via an institution to check access.
Rent this article via DeepDyve. Institutional subscriptions. Armstrong, D. PubMed CAS Google Scholar. Berger, M. Effects of starvation, diabetes, fatty acids, acetoacetate insulin and exercise on glucose uptake and disposition. Bergstrom, J.
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The liver, a storehouse of the sugar-forming glycogen, is not primarily concerned in the hypoglycemic action of insulin, for the characteristic effect of the latter continues even after exclusion of the hepatic tissues. Artificial Intelligence Resource Center.
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Carbohydrate metabolism is the whole of Carbohydrate metabolism in muscle biochemical un responsible Carbohyddrate Carbohydrate metabolism in muscle on formationbreakdownand interconversion metsbolism carbohydrates in living organisms. Carbohydrates are central to many essential metabolic Carbohydrate metabolism in muscle. Humans can consume Peanut butter energy bars variety of muscls, digestion breaks down complex carbohydrates into simple monomers monosaccharides : glucosefructosemannose and galactose. After resorption in the gutthe monosaccharides are transported, through the portal veinto the liver, where all non-glucose monosacharids fructose, galactose are transformed into glucose as well. Glycolysis is the process of breaking down a glucose molecule into two pyruvate molecules, while storing energy released during this process as adenosine triphosphate ATP and nicotinamide adenine dinucleotide NADH. Glycolysis consists of ten steps, split into two phases.
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Blood Glucose Control and Supply to Skeletal Muscle During ExerciseCarbohydrate metabolism in muscle -
The present review addresses the role of exogenous CHO utilisation during exercise, with a focus on potential mechanisms involved, from glucose uptake to glucose delivery and oxidation at the different stages of regulation.
A number of potential barriers were identified, including gastric emptying, intestinal absorption, blood flow splanchnic and muscle , muscle uptake and oxidation. The relocation of glucose transporters plays a key role in the regulation of CHO, particularly in epithelial cells and subsequent transport into the blood.
Limitations are also apparent when CHO is infused, particularly with regards to blood flow and uptake within the muscle. We highlight a number of potential barriers involved with the regulation of both ingested and infused CHO during exercise.
Future work on the influence of longitudinal training within the regulation processes such as the gut is warranted to further understand the optimal type, dose and method of CHO delivery to enhance sporting performance.
Aitor Viribay, Juan M. Alcantara, … Arkaitz Castañeda-Babarro. Mishti Khatri, Robert J. Naughton, … Liam Corr. Emma Moore, Joel T. Fuller, … Clint R. Carbohydrates CHO and fats are the two major energy sources that fuel muscle during prolonged steady state and intermittent exercise.
More recently, Cermack and Loon have explored and collated studies which demonstrate similar overall conclusions. These improvements could be due to a number of factors such as stimulation of CHO receptors in the oral cavity and thereby modulating neural drive and attenuating perceived exertion Carter et al.
In addition, CHO intake during exercise not only increases oxidation but may spare the use of the limited muscle glycogen and thereby improve performance or capacity Stellingwerff et al. Stellingwerff and Cox proposed a likelihood of performance benefits with CHO ingestion when exercise was longer than 2-h but not necessarily if the bout was less than 1-h.
They concluded that the primary mechanism by which CHO enhances endurance performance was due to a high rate of CHO delivery resulting in elevated rates of CHO oxidation.
Consequently, numerous investigations have explored the promotion of CHO delivery to the muscle using high levels of a single source of CHO or by ingesting multiple transportable CHO such as glucose: fructose combinations Newell et al.
The issue with ingesting large amounts of CHO during performance particularly running and cycling to a lesser extent is that the gastrointestinal system is compromised and may lead to unwarranted symptoms such as gut pain, flatulence, diarrhea, and vomiting.
Studies whereby glucose delivery to the muscle during exercise is via infusion invariably results in higher levels of total CHO oxidation i.
This review briefly explores the likely causes of impaired glucose delivery to muscle during exercise from ingested and infused sources, the rates of both total CHO oxidation as well as exogenous glucose oxidation during exercise, before examining some regulatory considerations within muscle.
When CHO are ingested during exercise, the source passes through the mouth, stomach and into the small intestine where digestion is complete and absorption takes place. The monosaccharide that then enters into the hepatic portal system passes through the splanchnic bed and then into general circulation where it arrives at the muscles cells for oxidation.
It is highly unlikely that CHO is absorbed across the mouth and so is unlikely to affect oxidation. Indeed, the so-called mouth rinsing studies have not shown any changes in CHO oxidation during exercise bouts lasting between 60 and 90 min Wright and Davison Previous research has demonstrated that the energy content and osmolality of the ingested solution plays a key role in the rate of gastric emptying Vist and Maughan Solutions of low osmolality empty from the stomach at a faster rate than those with a high osmolality.
Beverages with as little as 2. The amount of CHO delivery to the intestine and the rate of exogenous CHO oxidation increases linearly with increasing CHO concentration despite the decrease in gastric emptying, although only solutions with low or isotonic CHO content should be imbibed during prolonged exercise as they are emptied more rapidly and help hydrate.
When the requirement is for a greater amount of CHO during strenuous exercise, this can be achieved with a more concentrated CHO source irrespective of the reduced gastric emptying Foster The type of CHO ingested appears immaterial for gastric emptying since osmolality is more important El-Sayed et al.
The majority of CHO drinks ingested during exercise are monosaccharides or so-called simple sugars such as glucose, fructose, and galactose, although disaccharides such as sucrose, and polysaccharides such as maltodextrins and even starch have been employed. The disaccharides and polysaccharides are required to be digested to their respective monosaccharides before absorption across the gut in the small intestine can occur.
Evidence is available that the number of SGLT1 transporters are in abundance when compared with GLUT5 transporters, and is a factor as to why glucose uptake across the intestine is greater and faster than fructose Jeukendrup Indeed, high concentrations of fructose ingested during running-based activities, in particular, have been reported to contribute to increases in gastrointestinal problems — notably diarrhea, abdominal pain, and flatulence Prado de Oliveira et al.
Figure 2 illustrates the uptake of glucose, galactose, and fructose across the intestinal cells and into splanchnic circulation. Although beyond the scope of this review, high CHO dietary intake has been shown to upregulate SGLT1 transporters in mice Ferraris et al.
To date, no studies have explored this within a human cohort. Schematic illustrating the uptake of glucose, galactose, and fructose across the intestinal cells and into splanchnic circulation.
The interplay between exercise, the gut and CHO oxidation was the focus of an interesting paper by Rehrer et al. Drinks were consumed at 0, 20, 40, and 60 min and included water, 4. The CHO drinks were enriched with 13 C to measure exogenous CHO oxidation. Gastric volume was measured at 80 min.
The total amount of CHO ingested over the min were The oxidation of the exogenous CHO accounted for Much of the ingested CHO was not oxidized. The discrepancy between amounts ingested and amounts oxidized could not account for a delay in gastric emptying.
There were large differences in the total amount of CHO being emptied from the stomach with the different treatments, but the differences in total exogenous CHO utilized were small in comparison.
With the 4. They concluded that even in the face of the stimulatory effects of exercise on hepatic glycogenolysis and gluconeogenesis, the liver remains the major site of retention and disposal of an ingested glucose meal.
Fructose is taken up by the liver and undergoes either oxidation or is converted to glucose and lactate, which are then transported from the liver for muscle and other tissue to utilize. During exercise there is a reduction in splanchnic blood flow Knight et al. This is another possible factor to consider vis a vis utilisation of ingested CHO.
Once ingested glucose is in the general circulation, it can be taken up into muscle for oxidation. Glucose does not freely diffuse into muscle, rather it is taken across the plasma membrane using a glucose transporter GLUT4 , which normally resides in intracellular vesicles and is translocated to the plasma membrane as a consequence of signaling mechanisms.
A brief description of glucose transport across the sarcolemma is discussed later in the present review. Consequently, on reflection, the CHO ingested has to empty from the stomach rapidly, be digested and reduced to monosaccharides if in a complex form, get absorbed across the gut wall, pass into the body circulatory system from the splanchnic region, and then get transported across the muscle membrane before oxidation is possible.
Highlighting a magnitude of barriers and potential limiting factors preceding the utilisation of CHO during exercise Rosset et al. The maximal rates of exogenous glucose oxidation during exercise have consistently observed to be approximately 1.
Ingestion of disaccharides and short-chain glucose polysaccharides such as maltose and maltodextrins result in similar maximal oxidation rates as glucose. Since glucose polysaccharides are required to be digested before absorption and yet maximal rates of oxidation are similar to glucose, this would indicate that pre-absorptive factors are not limiting.
This hypothesis was primarily based on multiple intestinal segmentations experiments showing limited absorption of concentrated glucose solutions Shi et al.
Another physiological effect of exercise, decreased splanchnic blood flow, may also limit intestinal absorption capacity. Yet, in absence of invasive direct assessments of glucose flows across the intestinal barrier, the idea that intestinal absorption limits exogenous glucose oxidation during exercise remains a hypothesis.
The plateau in exogenous glucose oxidation may also result from hepatic limitations. The route for ingested CHO is to follow portal circulation to the liver, where they can either be stored, metabolized or pass to the systemic circulation. The liver is also known to play a pivotal role in the maintenance of euglycemia through releasing the precise amount of glucose required to match extrahepatic use Moore et al.
Hence, the factors responsible for the limitation in exogenous glucose oxidation during exercise remain unclear, but probably not restricted to intestinal glucose absorption.
For a more comprehensive treatise on the matter of the CHO intake, the gastrointestinal tract and exercise, it is worth reading Rosset et al. However, infusing glucose directly into a vein disposes of the need for gut transport and other inherent problems. Previous work in which we have been involved using the hyperglycemic glucose clamp technique to observe metabolic changes during intense bouts of exercise, clearly demonstrated that maintained hyperglycemia by glucose infusion resulted in a maximal glucose utilisation rate GUR of 1.
Sites involved in the regulation of muscle glucose uptake during this process include glucose delivery to muscle from the capillary bed and across the interstitium, transport of glucose into the muscle by GLUT4, and phosphorylation of glucose within the muscle by hexokinase II HKII.
Muscle blood flow, capillary recruitment, and transport across the endothelial wall determine glucose movement from the blood to the interstitium, whilst plasma membrane GLUT4 content determines glucose transport into the cell, and muscle HKII activity determines the capacity to phosphorylate glucose and enable cell processing Kusters and Barrett, ; Messina et al.
Figure 3 illustrates the processes of glucose delivery and transport. Since glucose uptake is the product of blood flow and the arteriovenous glucose difference, the increase in blood flow is quantitatively the major contributor to the exercise-induced increase in muscle glucose uptake.
This is particularly apparent since an increase in blood glucose concentration has been demonstrated to equate to a parallel increase in interstitial glucose concentration during exercise, and that skeletal muscle contraction results in an increase in the diffusion coefficient of glucose within the interstitial space MacLean et al.
The authors also found higher lactate concentrations within the interstitial space compared to that within the venous and arterial plasma. This suggests that the diffusion across the interstitial space, particularly during exercise, may be a possible barrier for glucose transport.
In addition to the large increase in flow to contracting skeletal muscle during exercise, there is also recruitment of capillaries which increases the available surface area for glucose delivery towards the interstitium via GLUT1.
The regulation of blood flow to skeletal muscle is tightly coupled to the metabolic demand for oxygen with a change in oxygen requirement leading to a proportional change in blood flow.
The precisely regulated control of blood flow serves to minimize the work of the heart while ensuring adequate oxygen supply to the working muscle. Skeletal muscle blood flow can increase up to fold from rest to intense, dynamic exercise Andersen and Saltin Given the limitation in maximal cardiac output, the heart can only supply a fraction of working muscles with maximal blood flow, and during hard aerobic exercise involving larger muscle mass, vascular conductance has to be well regulated or blood pressure may fall Gleimann et al.
The overall regulation of skeletal muscle blood flow is achieved through a balance between, on one hand, sympathetic vasoconstriction and circulating vasoconstrictors, and on the other hand vasodilators derived from cells in the skeletal muscle tissue.
It is established that elevations in insulin lead to an increase in blood flow and thus glucose uptake Baron ; DeFronzo et al. This process involves endothelium-derived nitric oxide NO which is known to regulate the transport of insulin and uptake of glucose by several tissues including skeletal muscle.
Nitric oxide enhances flow-mediated vasodilation and improves the delivery of nutrients such as glucose. Conversely, both high glucose and insulin stimulate the transport of L-arginine and increase NO production in vascular endothelial cells Sobrevia et al.
In addition, insulin has been shown to stimulate skeletal muscle blood flow and enhance vasodilation by increasing NO release Roy et al. Taken together, studies have demonstrated that elevations in insulin concentrations lead to an increase in blood flow which is mediated through NO production, leading to increased glucose uptake.
What has been known for many years is that muscle glucose utilisation increases despite decreased insulin, because exercise causes translocation of GLUT4 glucose transporters from a different pool than insulin, and the exercise-induced signaling of glucose utilisation is independent of insulin signaling.
Furthermore, increased peripheral blood flow augments total insulin delivery to muscle and so compensates at least in part for the decreased plasma insulin concentrations.
This also explains why the insulin and exercise effects are additive Marliss and Vranic Blood glucose concentration is another important determinant of muscle glucose uptake during exercise.
Since glucose uptake across an exercising limb follows saturation kinetics with a Km found to be 10 mM during knee-extension exercise in humans Richter and Hargreaves , changes in plasma glucose concentration translate almost directly into proportional changes in leg glucose uptake.
During prolonged exercise, liver glucose output is reduced and hypoglycemia can limit muscle glucose uptake Felig et al. In contrast, increasing arterial glucose availability, by ingestion of CHO-containing beverages or by infusion, results in increased muscle glucose uptake and oxidation during prolonged exercise Jeukendrup et al.
In terms of high-intensity exercise, Schrader et al. In addition, RER remained significantly higher during the recovery period for the CHO supplementation group. This suggests that elevated insulin and potential increases in blood flow due to higher blood glucose may be important.
It has been known for many years that muscle glucose transport is carrier mediated and that the specific transport proteins responsible for insulin- and contraction-stimulated glucose transport in skeletal muscle have been identified Charron et al.
GLUT1 is generally expressed and is thought to be responsible for the basal uptake of glucose. Hence it is depicted in Fig. GLUT4 on the other hand is expressed most abundantly in adipose tissue and skeletal muscle.
GLUT4 resides in storage vesicles within the cell and are directed to fuse with the plasma membrane through both an increase in circulating blood glucose and exercise per se Richter and Hargreaves In the case of an increase in blood glucose, insulin concentrations are elevated. Insulin binds with its receptor and results in an increase in protein kinase B Akt , thereby promoting GLUT4 translocation.
The GLUT4 translocation process is complex, involving numerous cellular processes Fig. When skeletal muscles are stimulated simultaneously by contraction and insulin treatments, there are additive effects on glucose transport.
Consistent with these findings, the combination of exercise and insulin can have additive effects on GLUT4 translocation to the sarcolemma. These data support the concept that there are different mechanisms leading to the stimulation of muscle glucose transport by exercise and insulin.
However, for a more detailed exploration on this topic it is worth consulting Egan and Zierath , Mul et al. Schematic illustrating the GLUT4 translocation process during both a rest and b exercise. The relationship between GLUT4 and muscle fibre type has been reported and signified that Type1 fibres have a slightly greater content of GLUT4 than Type IIA and Type IIX in the vastus lateralis though not in soleus or triceps brachii Daugaard and Richter These findings show that GLUT4 expression is not dependent on fibre type per se but is muscle dependent, otherwise similar results would accrue between vastus and triceps brachii.
However, what has been definitively shown is that athletes have greater levels of GLUT4 than untrained individuals Andersen et al. These data reflect the low level of activity during training in which predominantly Type I fibres are recruited.
It is possible that a training intensity in which all fibres were recruited could show similar enhancement of GLUT4 across all fibre types. Once inside the muscle cell, glucose is immediately converted to glucosephosphate GP using HKII.
The rapidity of conversion of glucose to GP is a potential barrier to the rate of uptake of glucose. HKII is the second step of glucose utilization in insulin-sensitive tissues and may be considered rate-limiting under conditions where glucose transport is maximally stimulated Katz et al.
Skeletal muscle HKII mRNA levels and enzymatic activity are decreased when insulin is low or when insulin signaling is impaired. Inhibition of HKII is achieved through product inhibition by GP. If GP cannot be removed at a sufficient rate during exercise as in the case of maximal intensity bouts when glycogenolysis is favoured, a build-up of GP results.
The effect is product inhibition of HKII with a resultant attenuation of glucose uptake. At the start of exercise, there is evidence of an elevation of glucose within a muscle which demonstrates inhibition of HKII Richter and Hargreaves This is probably due to preferential use of muscle glycogen at the start of exercise thereby elevating GP; although as the exercise duration increases enhanced glucose uptake is observed.
Consequently, a concomitant reduction in intra-muscle glucose, probably due to reduced GP and hence increased HKII activity, results. It is also worth noting that starting exercise with a high muscle glycogen content produces a reduction in glucose uptake since muscle glycogenolysis is favoured, and as the glycogen levels are reduced with exercise there is an increase in glucose uptake.
It would appear that HKII is a regulatory factor for glucose uptake either during maximal exercise or at the onset of exercise but unlikely at other time points in steady-state exercise. So, which of the processes of delivery, transport, and metabolism are limiting factors for glucose uptake and oxidation in a muscle cell?
The answer appears to be dependent on the level of exercise intensity. At maximal exercise intensity, delivery is clearly an issue due to cardiac output being unable to fully meet the demands, but equally inhibition of HKII by GP would result in a reduced ability of muscle to take up and utilize the exogenous glucose.
During steady-state bouts of exercise, where blood flow matches the oxygen demands of the cell, it is likely that delivery of glucose may be enhanced by increasing insulin through glucose intake and thereby promoting increased capillary flow.
The complexity and diversity of the entire hormonal response to exercise are too large to be covered in detail here, and so the focus on the metabolic effects of exercise in relation with the endocrine response will be confined to insulin, glucagon, and the sympathoadrenal system.
An early but classic description of the hormonal response to exercise was comprehensively reviewed by Galbo , and the findings are still relevant today. The sympathoadrenal system releases the hormones epinephrine, norepinephrine and cortisol, and although norepinephrine is often referred to as a hormone it is more akin to the action of a neurotransmitter.
Increases in sympathetic nervous activity as a function of exercise have been reported to be linked to increased activity of the motor cortex of the brain Jansson and Kaijser ; Victor et al. The effects of exercise on circulating catecholamine release can be summarized as follows: exercise induces an increase in catecholamines that is observed across a wide range of exercise modalities Galbo et al.
The exercise-induced increase in catecholamine concentration is sufficient to stimulate glycogenolysis in both the liver Kjaer et al. During exercise, the effects of increasing plasma epinephrine concentration on the metabolic response in muscle report an increase in CHO utilisation Richter et al.
The effects of adrenergic stimulation on CHO metabolism have also been examined in relationship with glucose uptake by skeletal muscle. Infusion of epinephrine has been reported to decrease glucose uptake Watt et al.
Studies in which a CHO is ingested or glucose infused have demonstrated that catecholamines are somewhat suppressed with increases in blood glucose and insulin MacLaren et al. The greater the blood glucose, the higher the insulin and the lower the catecholamines.
This is considered to be feedback-regulated by signals associated with the increased demand by the exercising muscles, causing responses that increase glucose production to match glucose utilisation.
During exercise, insulin secretion is inhibited below fasting levels by adrenergic receptor activation, both via the sympathetic innervation of the islets and by circulating catecholamines Marliss and Vranic The decrease of insulin secretion is important because it increases glucose production by the liver by sensitizing it to glucagon Zinker et al.
It is established that the decreases in insulin and unchanged or increased glucagon account for the corresponding increases in glucose production Wasserman et al. Thus, the ratio of glucagon to insulin is the major regulator of glucose production during moderate exercise.
Their increase during 40 min of moderate exercise are modest and predicted to have limited effects. In fact, with an infusion of glucose to attain hyperglycaemia, the insulin levels may be elevated fourfold with ingestion MacLaren et al.
Indeed, in our recent publication with insulin infusion a fold increase in insulin concentration was achieved Mohebbi et al. Schrader et al.
The consequence is that CHO oxidation and use is promoted whilst fat oxidation is attenuated, and as mentioned in the previous section could be in some part due to enhanced capillarisation.
The progression from CHO ingestion to its oxidation and use as an energy source is a complex process, one which Rosset et al.
Another study, also using 14 C, found a slightly higher finding of 0. These rather low values of the rate of exogenous oxidation contrast sharply with other reported findings using 13 C isotopes is subsequent years and may have been an anomaly in the techniques applied at that time as well as the lower exercise intensities employed.
The results from some of the earlier studies using 13 C and exercise provided rates of exogenous CHO oxidation between 0. Many subsequent and more recent investigations have produced similar findings to the classical earlier studies i.
that the rates of exogenous CHO oxidation seem to be around 0. However, some types of CHO are more readily oxidized than others Currell and Jeukendrup Clearly, glucose is the yardstick by which other CHO sources may be compared since it requires no digestion and is readily absorbed. Consequently, many investigations have used comparison with glucose as a measure of their efficacy.
There are clear findings that maltose, sucrose, maltodextrins, and glucose polymers result in very similar rates of exogenous oxidation Jeukendrup and Jentjens Even high molecular weight glucose polymers Rowlands et al.
So, it appears that digestion and absorption of these various CHO sources is not an issue, although any highly concentrated form of a CHO may affect gastric emptying and cause GI disturbances.
Fructose, on the other hand, has readily exhibited an inferior rate of oxidation in most reported studies Jandrain et al. This is in part due to the slower absorption of fructose across the intestinal cells due to the diffusion dependent on a concentration gradient, as well as the fact that almost all the fructose is taken up by the liver in a first-pass Tappy and Le The liver then converts the fructose to glucose and lactate for further distribution.
Likewise, galactose has been reported to have a significantly lower rate of oxidation when compared with glucose Leijssen et al. However, a single 75 g bolus of CHO was provided rather than a continuous supply. It is likely that the faster absorption of glucose resulted in the elevated oxidation earlier on whereas the slower uptake of galactose resulted in higher oxidation after 90 min.
It is suggested that by feeding a single CHO source e. glucose, fructose or maltodextrins at high rates, the specific transporter proteins that aid in absorbing that CHO from the intestine become saturated. Once these transporters are saturated, feeding more of that CHO will not result in greater intestinal absorption and increased oxidation rates.
Shi and colleagues suggested that the ingestion of CHO that use different transporters might increase total CHO absorption. Subsequently, a series of studies using different combinations of CHO in effect glucose and fructose at a ratio of to determine their effects on exogenous CHO oxidation were undertaken Jentjens and Jeukendrup However, ingestion of glucose plus fructose resulted in a rate of exogenous CHO oxidation amounting to 1.
With this regimen, exogenous CHO oxidation peaked at 1. More recently, investigations have been conducted on CHO sources which have been encapsulated in a hydrogel. The rationale is that encapsulation of high CHO dose would not compromise gastric emptying and thereby result in reduced GI discomfort.
Although in its infancy, early findings do not appear to show higher rates of exogenous CHO oxidation compared with glucose or maltodextrin Baur et al.
It should be mentioned that these studies did not examine exogenous oxidation but rather total CHO oxidation. There is scope to explore the impact of such encapsulation of a CHO source with labelled 13 C and thereby determine the rates of exogenous oxidation, although to date no such investigation has been reported.
Any factors which purport to enhance intestinal absorption during exercise would seem eminently sensible to pursue. To this end, a recent study examined the potential efficacy of 4 weeks of probiotic supplementation on subsequent oxidation of exogenous maltodextrin Pugh et al.
The results highlighted a small but significant increase in exogenous CHO oxidation after supplementation compared with placebo, although the authors were unable to confirm whether intestinal absorption was a factor. Furthermore, the rates of oxidation after supplementation or placebo were 0.
The hyperglycaemic glucose clamp technique was devised by DeFronzo et al. Although the focus of this technique has been mainly applied to clinical settings in relation to diabetes and metabolic syndrome Vandemeulebroucke et al.
The focus of the studies employing the hyperglycaemic clamp during exercise has been to report total CHO oxidation as well as utilization of the infused glucose. Additionally, the effects on circulating hormones and muscle glycogen use have been reported in some of the investigations.
An important factor to consider with hyperglycaemic clamp studies is that by clamping at glucose concentrations of 10—12 mM there is complete cessation of liver glucose output i. the blood glucose levels are maintained entirely due to exogenous infused CHO and do not arise from the liver output via glycogenolysis or gluconeogenesis Hawley et al.
Therefore, glycolysis generates energy for the cell and creates pyruvate molecules that can be processed further through the aerobic Krebs cycle also called the citric acid cycle or tricarboxylic acid cycle ; converted into lactic acid or alcohol in yeast by fermentation; or used later for the synthesis of glucose through gluconeogenesis.
When oxygen is limited or absent, pyruvate enters an anaerobic pathway. In these reactions, pyruvate can be converted into lactic acid.
In this reaction, lactic acid replaces oxygen as the final electron acceptor. Anaerobic respiration occurs in most cells of the body when oxygen is limited or mitochondria are absent or nonfunctional.
For example, because erythrocytes red blood cells lack mitochondria, they must produce their ATP from anaerobic respiration. This is an effective pathway of ATP production for short periods of time, ranging from seconds to a few minutes. The lactic acid produced diffuses into the plasma and is carried to the liver, where it is converted back into pyruvate or glucose via the Cori cycle.
Similarly, when a person exercises, muscles use ATP faster than oxygen can be delivered to them. They depend on glycolysis and lactic acid production for rapid ATP production.
The NADH and FADH2 pass electrons on to the electron transport chain, which uses the transferred energy to produce ATP. As the terminal step in the electron transport chain, oxygen is the terminal electron acceptor and creates water inside the mitochondria. Figure 3. Click to view a larger image.
The process of anaerobic respiration converts glucose into two lactate molecules in the absence of oxygen or within erythrocytes that lack mitochondria. During aerobic respiration, glucose is oxidized into two pyruvate molecules.
The pyruvate molecules generated during glycolysis are transported across the mitochondrial membrane into the inner mitochondrial matrix, where they are metabolized by enzymes in a pathway called the Krebs cycle Figure 4.
The Krebs cycle is also commonly called the citric acid cycle or the tricarboxylic acid TCA cycle. During the Krebs cycle, high-energy molecules, including ATP, NADH, and FADH2, are created.
NADH and FADH2 then pass electrons through the electron transport chain in the mitochondria to generate more ATP molecules. Figure 4. During the Krebs cycle, each pyruvate that is generated by glycolysis is converted into a two-carbon acetyl CoA molecule. The acetyl CoA is systematically processed through the cycle and produces high- energy NADH, FADH2, and ATP molecules.
The three-carbon pyruvate molecule generated during glycolysis moves from the cytoplasm into the mitochondrial matrix, where it is converted by the enzyme pyruvate dehydrogenase into a two-carbon acetyl coenzyme A acetyl CoA molecule. This reaction is an oxidative decarboxylation reaction. Acetyl CoA enters the Krebs cycle by combining with a four-carbon molecule, oxaloacetate, to form the six-carbon molecule citrate, or citric acid, at the same time releasing the coenzyme A molecule.
The six-carbon citrate molecule is systematically converted to a five-carbon molecule and then a four-carbon molecule, ending with oxaloacetate, the beginning of the cycle.
Along the way, each citrate molecule will produce one ATP, one FADH2, and three NADH. The FADH2 and NADH will enter the oxidative phosphorylation system located in the inner mitochondrial membrane. In addition, the Krebs cycle supplies the starting materials to process and break down proteins and fats.
To start the Krebs cycle, citrate synthase combines acetyl CoA and oxaloacetate to form a six-carbon citrate molecule; CoA is subsequently released and can combine with another pyruvate molecule to begin the cycle again.
The aconitase enzyme converts citrate into isocitrate. In two successive steps of oxidative decarboxylation, two molecules of CO2 and two NADH molecules are produced when isocitrate dehydrogenase converts isocitrate into the five-carbon α-ketoglutarate, which is then catalyzed and converted into the four-carbon succinyl CoA by α-ketoglutarate dehydrogenase.
The enzyme succinyl CoA dehydrogenase then converts succinyl CoA into succinate and forms the high-energy molecule GTP, which transfers its energy to ADP to produce ATP. Succinate dehydrogenase then converts succinate into fumarate, forming a molecule of FADH2.
Oxaloacetate is then ready to combine with the next acetyl CoA to start the Krebs cycle again see Figure 4. For each turn of the cycle, three NADH, one ATP through GTP , and one FADH2 are created.
Each carbon of pyruvate is converted into CO2, which is released as a byproduct of oxidative aerobic respiration. The electron transport chain ETC uses the NADH and FADH 2 produced by the Krebs cycle to generate ATP. Electrons from NADH and FADH 2 are transferred through protein complexes embedded in the inner mitochondrial membrane by a series of enzymatic reactions.
In the presence of oxygen, energy is passed, stepwise, through the electron carriers to collect gradually the energy needed to attach a phosphate to ADP and produce ATP.
The role of molecular oxygen, O 2 , is as the terminal electron acceptor for the ETC. This means that once the electrons have passed through the entire ETC, they must be passed to another, separate molecule. This is the basis for your need to breathe in oxygen.
Without oxygen, electron flow through the ETC ceases. Figure 5. The electrons released from NADH and FADH 2 are passed along the chain by each of the carriers, which are reduced when they receive the electron and oxidized when passing it on to the next carrier.
Each of these reactions releases a small amount. The accumulation of these protons in the space between the membranes creates a proton gradient with respect to the mitochondrial matrix. Also embedded in the inner mitochondrial membrane is an amazing protein pore complex called ATP synthase.
This rotation enables other portions of ATP synthase to encourage ADP and P i to create ATP. In accounting for the total number of ATP produced per glucose molecule through aerobic respiration, it is important to remember the following points:.
Therefore, for every glucose molecule that enters aerobic respiration, a net total of 36 ATPs are produced see Figure 6. Figure 6. Carbohydrate metabolism involves glycolysis, the Krebs cycle, and the electron transport chain. Gluconeogenesis is the synthesis of new glucose molecules from pyruvate, lactate, glycerol, or the amino acids alanine or glutamine.
This process takes place primarily in the liver during periods of low glucose, that is, under conditions of fasting, starvation, and low carbohydrate diets. So, the question can be raised as to why the body would create something it has just spent a fair amount of effort to break down?
Certain key organs, including the brain, can use only glucose as an energy source; therefore, it is essential that the body maintain a minimum blood glucose concentration. When the blood glucose concentration falls below that certain point, new glucose is synthesized by the liver to raise the blood concentration to normal.
Gluconeogenesis is not simply the reverse of glycolysis. There are some important differences Figure 7. Pyruvate is a common starting material for gluconeogenesis. First, the pyruvate is converted into oxaloacetate. Oxaloacetate then serves as a substrate for the enzyme phosphoenolpyruvate carboxykinase PEPCK , which transforms oxaloacetate into phosphoenolpyruvate PEP.
Although there are more reactions in the glycolytic pathway than in PCr hydrolysis, the production of ATP through anaerobic glycolysis is also activated in milliseconds.
Lactate accumulation can be measured in the muscle after only a 1-s contraction, and the contribution of anaerobic energy from PCr and anaerobic glycolysis is essentially equivalent after 6—10 s of intense exercise 4 , 24 , 40 Fig.
The capacity of the PCr energy store is a function of its resting content ~75 mmol per kg dry muscle and can be mostly depleted in 10—15 s of all-out exercise.
The anaerobic glycolytic capacity is approximately threefold higher ~ mmol per kg dry muscle in exercise lasting 30—90 s and is limited not by glycogen availability but instead by increasing intramuscular acidity. During the transition from rest to intense exercise, the substrate for increased aerobic ATP production is also muscle glycogen, and a small amount of the produced pyruvate is transferred into the mitochondria, where it is used to produce acetyl-CoA and the reducing equivalent NADH in the pyruvate dehydrogenase PDH reaction.
A good example is the enzyme PDH, which is kept in inactive form by resting levels of acetyl-CoA and NADH. The power of these resting regulators is weak compared with that of the heavy hitters in exercise. Instead, AMPK activation during exercise may be functionally more important for the postexercise changes in muscle metabolism and insulin sensitivity, and for mediating some of the key adaptive responses to exercise in skeletal muscle, such as mitochondrial biogenesis and enhanced glucose transporter GLUT 4 expression.
Considerable redundancy and complex spatial and temporal interactions among multiple intramuscular signalling pathways are likely to occur during exercise.
In future studies, these approaches should provide new insights into the molecular regulation of skeletal muscle energy metabolism during exercise. In this situation, there is time to mobilize fat and carbohydrate substrates from sources in the muscle as well as from the adipose tissue and liver Fig.
The muscles still rely on anaerobic energy for the initial 1—2 min when transitioning from rest to an aerobic power output, but then aerobic metabolism dominates. To produce the required ATP, the respiratory or electron-transport chain in the mitochondria requires the following substrates: reducing equivalents in the form of NADH and FADH 2 , free ADP, P i and O 2 Fig.
The respiratory and cardiovascular systems ensure the delivery of O 2 to contracting muscles, and the by-products of ATP utilization in the cytoplasm ADP and P i are transported back into the mitochondria for ATP resynthesis.
The processes that move ATP out of the mitochondria and ADP and P i back into the mitochondria are being intensely studied and appear to be more heavily regulated than previously thought 52 , In the presence of ample O 2 and ADP and P i in the mitochondria, the increase in ADP concentration with exercise is believed to activate the respiratory chain to produce ATP In terms of the metabolic pathways, the tricarboxylic acid TCA cycle in the mitochondria specializes in producing reducing equivalents and accepts acetyl-CoA mainly from carbohydrate and fat and other fuels to do so.
Substrate accumulation and local regulators fine-tune the flux through the dehydrogenases, and a third enzyme, citrate synthase, controls TCA-cycle flux. Additional NADH is produced both in the glycolytic pathway, after which it is shuttled from the cytoplasm into the mitochondria, and in the PDH reaction, which occurs in the mitochondria.
The transport protein GLUT4 facilitates the influx of glucose into cells, and increases in glucose delivery, secondary to enhanced muscle blood flow, and intramuscular glucose metabolism ensure that the gradient for glucose diffusion is maintained during exercise Translocation of GLUT4 is a fundamental event in exercise-induced muscle glucose uptake, and its regulation has been well studied Transport proteins for fat are also translocated to the muscle membrane mainly plasma membrane fatty acid—binding protein and mitochondrial membranes mainly fatty acid translocase FAT, also known as CD36 , where they transport fatty acids into cells and mitochondria 59 , The fatty acids that are transported into the cytoplasm of the cell and released from IMTG must also be transported across the mitochondrial membranes with the help of the carnitine palmitoyl transferase CPT I system and fat-transport proteins, mainly FAT CD36 61 , Once inside the mitochondria, fat enters the β-oxidation pathway, which produces acetyl-CoA and reducing equivalents NADH and FADH 2 , and the long-chain nature of fatty acids results in generation of large amounts of aerobic ATP Box 1.
In these situations, fuel use shifts to carbohydrate, and reliance on fat is decreased Fig. However, if the endurance event is extended, the liver and skeletal muscle glycogen stores may become exhausted, thereby requiring athletes to slow down.
Researchers have now identified several sites where fat metabolism is downregulated at high aerobic exercise intensities, including decreased fatty acid release from adipose tissue and therefore less fatty acid transport into cells; decreased activation of hormone-sensitive lipase and possibly adipose triglyceride lipase; less IMTG breakdown; and inhibition of CPT I activity as a result of small decreases in muscle pH, decreased CPT I sensitivity to carnitine and possibly low levels of cytoplasmic carnitine-reducing mitochondrial-membrane transport 37 , In many team sports, a high aerobic ability is needed for players to move about the field or playing surface, whereas sprints and anaerobic ATP , as dictated by the game, are added to the contribution of aerobic ATP.
This scenario is repeated many times during a game, and carbohydrate provides most of the aerobic fuel and much of the anaerobic fuel. Unsurprisingly, almost every regulatory aspect of carbohydrate metabolism is designed for rapid provision of ATP. Carbohydrate is the only fuel that can be used for both aerobic and anaerobic ATP production, and both systems are activated very quickly during transitions from rest to exercise and from one power output to a higher power output.
In addition, the processes that provide fatty acids to the muscles and the pathways that metabolize fat and provide ATP in muscles are slower than the carbohydrate pathways. However, in events requiring long periods of exercise at submaximal power outputs, fat can provide energy for long periods of time and has a much larger ATP-generating capacity than carbohydrate.
Fat oxidation also contributes energy in recovery from exercise or rest periods between activity. Another important aspect of metabolism in stop-and-go sports is the ability to rapidly resynthesize PCr when the exercise intensity falls to low levels or athletes rest.
In these situations, continued aerobic production of ATP fuels the regeneration of PCr such that it can be completely recovered in 60— s ref. This production is extremely important for the ability to repeatedly sprint in stop-and-go or intermittent sports.
Recovery from prolonged sprinting 20—s and sustained high glycolytic flux is slower, because the associated muscle acidity requires minutes, not seconds, to recover and can limit performance 4 , Importantly, other fuels can provide aerobic energy in cells during exercise, including amino acids, acetate, medium-chain triglycerides, and the ketones β-hydroxybutyrate and acetoacetic acid.
Although these fuels can be used to spare the use of fat and carbohydrate in some moderate-intensity exercise situations, they lack the rate of energy provision needed to fuel intense aerobic exercise, because the metabolic machinery for these fuels is not designed for rapid energy provision.
Alternative fuels cannot match carbohydrate in terms of the rate of aerobic energy provision 9 , and these fuels cannot be used to produce anaerobic energy in the absence of oxygen.
Sex may have roles in the regulation of skeletal muscle metabolism. Males and females are often assumed to respond similarly to acute exercise and exercise training, but most of the work cited in this Review involved male participants. Clear differences exist between males and females—including haemoglobin concentrations, muscle mass and reproductive-hormone levels—and have been shown to affect metabolism and exercise performance, thus making perfect comparisons between males and females very difficult.
The potential sex differences in metabolism are briefly mentioned in Box 3 , and more detailed discussion can be found in a review by Kiens One issue in the study of the regulation of exercise metabolism in skeletal muscle is that much of the available data has been derived from studies on males.
Although the major principles controlling the regulation of metabolism appear to hold true for both females and males, some differences have been noted.
Although one might argue that completely matching males and females is impossible when studying metabolism, early work with well-trained track athletes has reported no differences in skeletal muscle enzyme activity, fibre-type composition and fat oxidation between men and women , However, more recent work has reported that a larger percentage of whole-body fuel use is derived from fat in females exercising at the same relative submaximal intensity, and this effect is likely to be related to circulating oestrogen levels , , , , , In addition, supplementation with oestrogen in males decreases carbohydrate oxidation and increases fat oxidation during endurance exercise These results suggest that females may be better suited to endurance exercise than males.
Another area that has been investigated is the effects of menstrual phase and menstrual status on the regulation of skeletal muscle metabolism. Generally, studies examining exercise in the luteal and follicular phases have reported only minor or no changes in fat and carbohydrate metabolism at various exercise intensities , , , Additional work examining the regulation of metabolism in well-trained female participants in both phases of the menstrual cycle, and with varied menstrual cycles, during exercise at the high aerobic and supramaximal intensities commensurate with elite sports, is warranted.
Sports performance is determined by many factors but is ultimately limited by the development of fatigue, such that the athletes with the greatest fatigue resistance often succeed.
However, there can be a fine line between glory and catastrophe, and the same motivation that drives athletes to victory can at times push them beyond their limits.
Fatigue is the result of a complex interplay among central neural regulation, neuromuscular function and the various physiological processes that support skeletal muscle performance 1.
It manifests as a decrease in the force or power-producing capacity of skeletal muscle and an inability to maintain the exercise intensity needed for ultimate success.
Over the years, considerable interest has been placed on the relative importance of central neural and peripheral muscle factors in the aetiology of fatigue. All that I am, I am because of my mind.
Perhaps the two major interventions used to enhance fatigue resistance are regular training and nutrition 70 , and the interactions between them have been recognized We briefly review the effects of training and nutrition on skeletal muscle energy metabolism and exercise performance, with a focus on substrate availability and metabolic end products.
In relation to dietary supplements, we have limited our discussion to those that have been reasonably investigated for efficacy in human participants Regular physical training is an effective strategy for enhancing fatigue resistance and exercise performance, and many of these adaptations are mediated by changes in muscle metabolism and morphology.
Such training is also associated with the cardiovascular and metabolic benefits often observed with traditional endurance training One hallmark adaptation to endurance exercise training is increased oxygen-transport capacity, as measured by VO 2 max 78 , thus leading to greater fatigue resistance and enhanced exercise performance The other is enhanced skeletal muscle mitochondrial density 80 , a major factor contributing to decreased carbohydrate utilization and oxidation and lactate production 81 , 82 , increased fat oxidation and enhanced endurance exercise performance The capacity for muscle carbohydrate oxidation also increases, thereby enabling maintenance of a higher power output during exercise and enhanced performance Finally, resistance training results in increased strength, neuromuscular function and muscle mass 85 , effects that can be potentiated by nutritional interventions, such as increased dietary protein intake The improved performance is believed to be due to enhanced ATP resynthesis during exercise as a result of increased PCr availability.
Some evidence also indicates that creatine supplementation may increase muscle mass and strength during resistance training No major adverse effects of creatine supplementation have been observed in the short term, but long-term studies are lacking.
Creatine remains one of the most widely used sports-related dietary supplements. The importance of carbohydrate for performance in strenuous exercise has been recognized since the early nineteenth century, and for more than 50 years, fatigue during prolonged strenuous exercise has been associated with muscle glycogen depletion 13 , Muscle glycogen is critical for ATP generation and supply to all the key ATPases involved in excitation—contraction coupling in skeletal muscle Recently, prolonged exercise has been shown to decrease glycogen in rodent brains, thus suggesting the intriguing possibility that brain glycogen depletion may contribute to central neural fatigue Muscle glycogen availability may also be important for high-intensity exercise performance Blood glucose levels decline during prolonged strenuous exercise, because the liver glycogen is depleted, and increased liver gluconeogenesis is unable to generate glucose at a rate sufficient to match skeletal muscle glucose uptake.
Maintenance of blood glucose levels at or slightly above pre-exercise levels by carbohydrate supplementation maintains carbohydrate oxidation, improves muscle energy balance at a time when muscle glycogen levels are decreased and delays fatigue 20 , 97 , Glucose ingestion during exercise has minimal effects on net muscle glycogen utilization 97 , 99 , but increases muscle glucose uptake and markedly decreases liver glucose output , , because the gut provides most glucose to the bloodstream.
Importantly, although carbohydrate ingestion delays fatigue, it does not prevent fatigue, and many factors clearly contribute to fatigue during prolonged strenuous exercise. Because glucose is the key substrate for the brain, central neural fatigue may develop during prolonged exercise as a consequence of hypoglycaemia and decreased cerebral glucose uptake Carbohydrate ingestion exerts its benefit by increasing cerebral glucose uptake and maintaining central neural drive NH 3 can cross the blood—brain barrier and has the potential to affect central neurotransmitter levels and central neural fatigue.
Of note, carbohydrate ingestion attenuates muscle and plasma NH 3 accumulation during exercise , another potential mechanism through which carbohydrate ingestion exerts its ergogenic effect.
Enhanced exercise performance has also been observed from simply having carbohydrate in the mouth, an effect that has been linked to activation of brain centres involved in motor control Increased plasma fatty acid availability decreases muscle glycogen utilization and carbohydrate oxidation during exercise , , High-fat diets have also been proposed as a strategy to decrease reliance on carbohydrate and improve endurance performance.
Other studies have demonstrated increased fat oxidation and lower rates of muscle glycogen use and carbohydrate oxidation after adaptation to a short-term high-fat diet, even with restoration of muscle glycogen levels, but no effect on endurance exercise performance , If anything, high-intensity exercise performance is impaired on the high-fat diet , apparently as a result of an inability to fully activate glycogenolysis and PDH during intense exercise Furthermore, a high-fat diet has been shown to impair exercise economy and performance in elite race walkers A related issue with high-fat, low carbohydrate diets is the induction of nutritional ketosis after 2—3 weeks.
However, when this diet is adhered to for 3 weeks, and the concentrations of ketone bodies are elevated, a decrease in performance has been observed in elite race walkers The rationale for following this dietary approach to optimize performance has been called into question Although training on a high-fat diet appears to result in suboptimal adaptations in previously untrained participants , some studies have reported enhanced responses to training with low carbohydrate availability in well-trained participants , Over the years, endurance athletes have commonly undertaken some of their training in a relatively low-carbohydrate state.
However, maintaining an intense training program is difficult without adequate dietary carbohydrate intake Furthermore, given the heavy dependence on carbohydrate during many of the events at the Olympics 9 , the most effective strategy for competition would appear to be one that maximizes carbohydrate availability and utilization.
Nutritional ketosis can also be induced by the acute ingestion of ketone esters, which has been suggested to alter fuel preference and enhance performance The metabolic state induced is different from diet-induced ketosis and has the potential to alter the use of fat and carbohydrate as fuels during exercise.
However, published studies on trained male athletes from at least four independent laboratories to date do not support an increase in performance. Acute ingestion of ketone esters has been found to have no effect on 5-km and km trial performance , , or performance during an incremental cycling ergometer test A further study has reported that ketone ester ingestion decreases performance during a The rate of ketone provision and metabolism in skeletal muscle during high-intensity exercise appears likely to be insufficient to substitute for the rate at which carbohydrate can provide energy.
Early work on the ingestion of high doses of caffeine 6—9 mg caffeine per kg body mass 60 min before exercise has indicated enhanced lipolysis and fat oxidation during exercise, decreased muscle glycogen use and increased endurance performance in some individuals , , These effects appear to be a result of caffeine-induced increases in catecholamines, which increase lipolysis and consequently fatty acid concentrations during the rest period before exercise.
After exercise onset, these circulating fatty acids are quickly taken up by the tissues of the body 10—15 min , fatty acid concentrations return to normal, and no increases in fat oxidation are apparent.
Importantly, the ergogenic effects of caffeine have also been reported at lower caffeine doses ~3 mg per kg body mass during exercise and are not associated with increased catecholamine and fatty acid concentrations and other physiological alterations during exercise , This observation suggests that the ergogenic effects are mediated not through metabolic events but through binding to adenosine receptors in the central and peripheral nervous systems.
Caffeine has been proposed to increase self-sustained firing, as well as voluntary activation and maximal force in the central nervous system, and to decrease the sensations associated with force, pain and perceived exertion or effort during exercise in the peripheral nervous system , The ingestion of low doses of caffeine is also associated with fewer or none of the adverse effects reported with high caffeine doses anxiety, jitters, insomnia, inability to focus, gastrointestinal unrest or irritability.
Contemporary caffeine research is focusing on the ergogenic effects of low doses of caffeine ingested before and during exercise in many forms coffee, capsules, gum, bars or gels , and a dose of ~ mg caffeine has been argued to be optimal for exercise performance , The potential of supplementation with l -carnitine has received much interest, because this compound has a major role in moving fatty acids across the mitochondrial membrane and regulating the amount of acetyl-CoA in the mitochondria.
The need for supplemental carnitine assumes that a shortage occurs during exercise, during which fat is used as a fuel. Although this outcome does not appear to occur during low-intensity and moderate-intensity exercise, free carnitine levels are low in high-intensity exercise and may contribute to the downregulation of fat oxidation at these intensities.
However, oral supplementation with carnitine alone leads to only small increases in plasma carnitine levels and does not increase the muscle carnitine content An insulin level of ~70 mU l —1 is required to promote carnitine uptake by the muscle However, to date, there is no evidence that carnitine supplementation can improve performance during the higher exercise intensities common to endurance sports.
NO is an important bioactive molecule with multiple physiological roles within the body. It is produced from l -arginine via the action of nitric oxide synthase and can also be formed by the nonenzymatic reduction of nitrate and nitrite. The observation that dietary nitrate decreases the oxygen cost of exercise has stimulated interest in the potential of nitrate, often ingested in the form of beetroot juice, as an ergogenic aid during exercise.
Indeed, several studies have observed enhanced exercise performance associated with lower oxygen cost and increased muscle efficiency after beetroot-juice ingestion , , The effect of nitrate supplementation appears to be less apparent in well-trained athletes , , although results in the literature are varied Dietary nitrate supplementation may have beneficial effects through an improvement in excitation—contraction coupling , , because supplementation with beetroot juice does not alter mitochondrial efficiency in human skeletal muscle , and the results with inorganic nitrate supplementation have been equivocal , Lactate is not thought to have a major negative effect on force and power generation and, as mentioned earlier, is an important metabolic intermediate and signalling molecule.
Of greater importance is the acidosis arising from increased muscle metabolism and strong ion fluxes. In humans, acidosis does not appear to impair maximal isometric-force production, but it does limit the ability to maintain submaximal force output , thus suggesting an effect on energy metabolism and ATP generation Ingestion of oral alkalizers, such as bicarbonate, is often associated with increased high-intensity exercise performance , , partly because of improved energy metabolism and ionic regulation , As previously mentioned, high-intensity exercise training increases muscle buffer capacity 74 , A major determinant of the muscle buffering capacity is carnosine content, which is higher in sprinters and rowers than in marathon runners or untrained individuals Ingestion of β-alanine increases muscle carnosine content and enhances high-intensity exercise performance , During exercise, ROS, such as superoxide anions, hydrogen peroxide and hydroxyl radicals, are produced and have important roles as signalling molecules mediating the acute and chronic responses to exercise However, ROS accumulation at higher levels can negatively affect muscle force and power production and induce fatigue 68 , Exercise training increases the levels of key antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase , and non-enzymatic antioxidants reduced glutathione, β-carotene, and vitamins C and E can counteract the negative effects of ROS.
Whether dietary antioxidant supplementation can improve exercise performance is equivocal , although ingestion of N -acetylcysteine enhances muscle oxidant capacity and attenuates muscle fatigue during prolonged exercise Some reports have suggested that antioxidant supplementation may potentially attenuate skeletal muscle adaptation to regular exercise , , Overall, ROS may have a key role in mediating adaptations to acute and chronic exercise but, when they accumulate during strenuous exercise, may exert fatigue effects that limit exercise performance.
The negative effects of hyperthermia are potentiated by sweating-induced fluid losses and dehydration , particularly decreased skeletal muscle blood flow and increased muscle glycogen utilization during exercise in heat Increased plasma catecholamines and elevated muscle temperatures also accelerate muscle glycogenolysis during exercise in heat , , Strategies to minimize the negative effects of hyperthermia on muscle metabolism and performance include acclimation, pre-exercise cooling and fluid ingestion , , , To meet the increased energy needs of exercise, skeletal muscle has a variety of metabolic pathways that produce ATP both anaerobically requiring no oxygen and aerobically.
These pathways are activated simultaneously from the onset of exercise to precisely meet the demands of a given exercise situation. Although the aerobic pathways are the default, dominant energy-producing pathways during endurance exercise, they require time seconds to minutes to fully activate, and the anaerobic systems rapidly in milliseconds to seconds provide energy to cover what the aerobic system cannot provide.
Anaerobic energy provision is also important in situations of high-intensity exercise, such as sprinting, in which the requirement for energy far exceeds the rate that the aerobic systems can provide. This situation is common in stop-and-go sports, in which transitions from lower-energy to higher-energy needs are numerous, and provision of both aerobic and anaerobic energy contributes energy for athletic success.
Together, the aerobic energy production using fat and carbohydrate as fuels and the anaerobic energy provision from PCr breakdown and carbohydrate use in the glycolytic pathway permit Olympic athletes to meet the high energy needs of particular events or sports.
The various metabolic pathways are regulated by a range of intramuscular and hormonal signals that influence enzyme activation and substrate availability, thus ensuring that the rate of ATP resynthesis is closely matched to the ATP demands of exercise. Regular training and various nutritional interventions have been used to enhance fatigue resistance via modulation of substrate availability and the effects of metabolic end products.
The understanding of exercise energy provision, the regulation of metabolism and the use of fat and carbohydrate fuels during exercise has increased over more than years, on the basis of studies using various methods including indirect calorimetry, tissue samples from contracting skeletal muscle, metabolic-tracer sampling, isolated skeletal muscle preparations, and analysis of whole-body and regional arteriovenous blood samples.
However, in virtually all areas of the regulation of fat and carbohydrate metabolism, much remains unknown. The introduction of molecular biology techniques has provided opportunities for further insights into the acute and chronic responses to exercise and their regulation, but even those studies are limited by the ability to repeatedly sample muscle in human participants to fully examine the varied time courses of key events.
The ability to fully translate findings from in vitro experiments and animal studies to exercising humans in competitive settings remains limited. The field also continues to struggle with measures specific to the various compartments that exist in the cell, and knowledge remains lacking regarding the physical structures and scaffolding inside these compartments, and the communication between proteins and metabolic pathways within compartments.
A clear example of these issues is in studying the events that occur in the mitochondria during exercise. One area that has not advanced as rapidly as needed is the ability to non-invasively measure the fuels, metabolites and proteins in the various important muscle cell compartments that are involved in regulating metabolism during exercise.
Although magnetic resonance spectroscopy has been able to measure certain compounds non-invasively, measuring changes that occur with exercise at the molecular and cellular levels is generally not possible. Some researchers are investigating exercise metabolism at the whole-body level through a physiological approach, and others are examining the intricacies of cell signalling and molecular changes through a reductionist approach.
New opportunities exist for the integrated use of genomics, proteomics, metabolomics and systems biology approaches in data analyses, which should provide new insights into the molecular regulation of exercise metabolism.
Many questions remain in every area of energy metabolism, the regulation of fat and carbohydrate metabolism during exercise, optimal training interventions and the potential for manipulation of metabolic responses for ergogenic benefits.
Exercise biology will thus continue to be a fruitful research area for many years as researchers seek a greater understanding of the metabolic bases for the athletic successes that will be enjoyed and celebrated during the quadrennial Olympic festival of sport.
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Carbohyddate you for visiting nature. You are Carbohydrate metabolism in muscle Nutrient absorption in the duodenum browser version Carbohydrate metabolism in muscle limited support for CSS. Carbohydate obtain the best experience, we recommend you use a Carbohydrate metabolism in muscle up nuscle Carbohydrate metabolism in muscle browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. An Author Correction to this article was published on 10 September The continual supply of ATP to the fundamental cellular processes that underpin skeletal muscle contraction during exercise is essential for sports performance in events lasting seconds to several hours.
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