Energy yield of glycogen stores under anaerobic conditions
Under anaerobic conditions, the oxidation of glucose to lactate via anaerobic glycolysis yields two molecules of ATP.
Below, the yield of ATP from anaerobic oxidation of glucose released from glycogen by the action of glycogen phosphorylase (EC 184.108.40.206), and debranching enzyme (EC 220.127.116.11) is considered.
Note: glycogen phosphorylase releases about 90% of stored glucose in the form of glucose-1-phoshate (G-1-P), and debranching enzyme the remaining 10% in the form of glucose.
Glycogen phosphorylase and the oxidation of G-1-P under anaerobic conditions
Glycogen synthesis from glucose requires 2 ATP for each molecule of glucose.
The release of glucose-1-phosphate by the action of glycogen phosphorylase allows the recovery of one of the 2 molecules of ATP used in the preparatory phase of glycolysis. The anaerobic oxidation of glucose-6-phosphate, produced from glucose-1-phosphate (G-1-P) by the action of phosphoglucomutase (EC 18.104.22.168), yields therefore three molecules of ATP and not two, because:
one molecule of ATP, instead of two, is used in the preparatory phase of glycolysis, because hexokinase reaction (EC 22.214.171.124) is bypassed;
four molecules of ATP are produced in the payoff phase of glycolysis.
The cost-gain rate is 1/3, namely, there is an energy yield of about 66,7%.
The overall reaction is:
Glycogen(n glucose residues) + 3 ADP + 3 Pi → Glycogen(n-1 glucose residues) + 2 Lactate + 3 ATP
By considering the two molecules of ATP used in the synthesis of glycogen and the anaerobic oxidation of glucose-1-phosphate to lactate, there is a yield of one molecule of ATP for each molecule of glucose stored. The overall reaction is:
Glucose + ADP + Pi → 2 Lactate + ATP
Debranching enzyme and the oxidation of glucose under anaerobic conditions
By considering the glucose released by the action of debranching enzyme, the yield of ATP is zero because:
Glycogen phosphorylase and the oxidation of G-1-P under aerobic condition
The oxidation of glucose-6-phosphate, produced from glucose-1-phosphate by the action of phosphoglucomutase, to CO2 and H2O yields 31 molecules of ATP, and not 30, because only one molecule of ATP is used in the preparatory phase of glycolysis. The cost-gain rate is 1/31, namely, there is an energy yield of about 97%.
The overall reaction is:
Glycogen(n glucose residues) + 31 ADP + 31 Pi → Glycogen(n-1 glucose residues) + 31 ATP + 6 CO2 + 6 H2O
By considering the two molecules of ATP used in the synthesis of glycogen and the aerobic oxidation of glucose-1-phosphate to CO2 and H2O, there is a yield of 29 molecules of ATP for each molecule of glucose stored.
The overall reaction is:
Glucose + 29 ADP + 30 Pi → 29 ATP + 6 CO2 + 6 H2O
Debranching enzyme and the oxidation of glucose under aerobic condition
By considering the glucose released by the action of debranching enzyme, there is a yield of 30 molecules of ATP, because two molecules of ATP are used in the preparatory phase of glycolysis. The cost-gain rate is 2/30, namely, there is an energy yield of about 93,3%.
If we now consider the oxidation to CO2 and H2O of all glucose released from glycogen, there is an energy yield equal to:
Then, under aerobic conditions, there is an energy yield of 96%, hence, glycogen is a extremely efficient storage form of energy, with a gain of 36% compared to anaerobic conditions.
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Glycogen is an homopolysaccharide formed by units of glucose. Chemically similar to amylopectin, and therefore sometimes referred to as animal starch, compared to the latter it is more compact, extensively branched and larger, reaching a molecular weight up to 108 Da corresponding to about 600000 glucose molecules.
As in the amylopectin, glucose units in the main chain and in the lateral chains are linked by α-(1→4) glycosidic bonds. Lateral chains are joined to the main chain by an α-(1→6) glycosidic bond; unlike amylopectin branches are more frequent, approximately every 10 glucose units (rather than every 25-30 as in amylopectin) and are formed by a smaller numbers of glucose units.
Glycogen is located in the cytosol of the cell in the form of hydrated granules of diameter between 1 to 4 µm and forms complexes with regulatory proteins and enzymes responsible for its synthesis and degradation.
Glycogen, discovered in 1857 by French physiologist Claude Bernard, is the storage form of glucose, and therefore of energy, in animals in which it is present in the liver, muscle (skeletal and heart muscle) and in lower amounts in nearly all the other tissues and organs.
In humans it represents less than 1% of the body’s caloric stores (the other form of caloric reserve, much more abundant, is triacylglycerols stored in adipose tissue) and is essential for maintaining normal glycemia too.
It represents about 10% of liver weight and 1% of muscle weight; although it is present in a higher concentration in the liver, the total stores in muscle are much higher thanks to its greater mass (in a non-fasting 70 kg adult male there are about 100 g of glycogen in the liver and 250 g in the muscle).
Liver glycogen stores is a glucose reserve that hepatocyte releases when needed to maintain a normal blood sugar levels: if you consider glucose availability (in a non-fasting 70 kg adult male) there is about 10 grams or 40 kcal in body fluids while hepatic glycogen can supply, also after a fasting night, about 600 kcal.
In skeletal and cardiac muscle, glucose from glycogen stores remains within the cell and is used as an energy source for muscle work.
The brain contains a small amount of glycogen, primarily in astrocytes. It accumulates during sleep and is mobilized upon waking, therefore suggesting its functional role in the conscious brain. These glycogen reserves also provide a moderate degree of protection against hypoglycemia.
It has a specialized role in fetal lung type II pulmonary cells. At about 26 weeks of gestation these cells start to accumulate glycogen and then to synthesize pulmonary surfactant, using it as a major substrate for the synthesis of surfactant lipids, of which dipalmitoylphosphatidylcholine is the major component.
Glycogen and foods
It is absent from almost all foods because after an animal is killed it is rapidly broken down to glucose and then to lactic acid; it should be noted that the acidity consequently to lactic acid production gradually improves the texture and keeping qualities of the meat. The only dietary sources are oysters and other shellfish that are eaten virtually alive: they contain about 5% glycogen.
In humans, accumulation of glycogen is associated with weight gain due to water retention: for each gram of stored glycogen 3 grams of water are retained.
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An important energy source for working muscle is its glycogen store, whose level is correlated with the onset of fatigue.
The highly trained athlete not only has glycogen stores potentially higher but he is also able to synthesize it faster thanks to more efficient enzymes.
To synthesize glycogen it is necessary to ingest carbohydrates; but how many, which, when, and how often?
The two phases of muscle glycogen synthesis after exercise
In order to restore as quickly as possible muscle glycogen depots, it is useful to know that, as a result of training sessions that deplete muscle glycogento values below 75% those at rest and not fasting, glycogen synthesis occurs in two phases.
To know and therefore take advantage of the biphasicity is important for those athletes who are engaged in more daily training sessions, or who otherwise have little time for recovery between a high intensity exercise and the subsequent one (less than 8 hours), in order to maximize glycogen synthesis and achieve the optimal performance during a second close exercise session.
The two phases are characterized by:
a different sensitivity to circulating insulin levels;
a different velocity.
The first phase
The first phase, immediately following the end of an activity and lasting 30-60 minutes, is insulin-independent, i.e. glucose uptake by muscle cell as glycogen synthesis are independent from hormone action.
This phase is characterized by an elevated rate of synthesis that however decreases rapidly if you do not take in carbohydrates: the maximum rate is in the first 30 minutes, then declines to about one fifth in 60 minutes, and to about one ninth in 120 minutes from the end of exercise.
How is it possible to take advantage of this first phase to replenish muscle glycogen stores as much as possible? By making sure that the greatest possible amount of glucose arrives to muscle in the phase immediately following to the end of exercise, best if done within the first 30 minutes.
What to ingest?
High glycemic index, but easy to digest and absorb, carbohydrates.
Therefore, it is advisable to replace foods, even though of high glycemic index, that need some time for digestion and the subsequent absorption, with solutions/gel containing for example glucose and/or sucrose. These solutions ensure the maximal possible absorption rate and resupply of glucose to muscle because of they contain only glucose and are without fiber or anything else that could slow their digestion and the following absorption of the monosaccharide, that is, they are capable of producing high blood glucose levels in a relatively short time.
It is also possible to play on temperature and concentration of the solution to accelerate the gastric transit.
It should be further underlined that the use of these carbohydrate solutions is recommended only when the recovery time from a training/competition session causing significant depletion of muscle glycogen and the following one is short, less than 8 hours.
How many carbohydrates do you need?
Many studies has been conducted to find the ideal amount of carbohydrates to ingest.
If in post-exercise the athlete does not eat, glycogen synthesis rate is very low, while if he ingests adequate amounts of carbohydrates immediately after cessation of exercise, synthesis rate can reach a value over 20 times higher.
From the analysis of scientific literature it seems reasonable to state that, as a result of training sessions that deplete muscle glycogen stores as seen above (<75% of those at rest and not fasting), the maximum synthesis rate is obtained by carbohydrate intake, with high glycemic index and high digestion and absorption rates, equal to about 1.2 g/kg of body weight/h for the next 4-5 hours from the end of exercise.
In this way, the amount of glycogen produced is higher than 150% compared to the ingestion of 0.8 g/kg/h.
Because further increases, up to 1.6 g/kg/h, do not lead to further rise in glycogen synthesis rate, the carbohydrate amount equal to 1.2 g/kg/h can be considered optimum to maximize the resynthesis rate of muscle glycogen stores during post-exercise.
And the frequency of carbohydrate ingestion?
It was observed that if carbohydrates are ingested frequently, every 15-30 minutes, it seems there is a further stimulation of muscle glucose uptake as of muscle glycogen replenishment compared with ingestion at 2-hours intervals. Particularly, ingestions in the first post-exercise hours seem to optimize glycogen levels.
The second phase
The second phase begins from the end of the first, lasts until the start of the last meal before the next exercise (hence, from several hours to days), and is insulin-dependent i.e. muscle glucose uptake and glycogen synthesis are sensitive to circulating hormone levels.
Moreover, you observe a significant reduction in muscle glycogen synthesis rate: with adequate carbohydrate intake the synthesis rate is at a value of about 10-30% lower than that observed during the first phase.
This phase can last for several hours, but tends to be shorter if:
In order to optimize the resynthesis rate of glycogen, experimental data indicate that meals with high glycemic index carbohydrates are more effective than those with low glycemic index carbohydrates; but if between a training/competition session and the subsequent one days and not hours spend, the evidences do not favor high glycemic index carbohydrates as compared to low glycemic index ones as long as an adequate amount is taken in.
Muscle glycogen synthesis rate and ingestion of carbohydrates and proteins
The combined ingestion of carbohydrates and proteins (or free insulinotropic amino acids) allows to obtain post-exercise glycogen synthesis rate that does not significantly differ from that obtained with larger amounts of carbohydrates alone. This could be an advantage for the athlete who may ingest smaller amount of carbohydrates, therefore reducing possible gastrointestinal complications commons during training/competition afterward to their great consumption.
From the analysis of scientific literature it seems reasonable to affirm that, after an exercise that depletes at least 75% of muscle glycogen stores, you can obtain a glycogen synthesis rate similar to that reached with 1.2 g/kg/h of carbohydrates alone (the maximum obtainable) with the coingestion of 0.8 g/kg/h of carbohydrates and 0.4 g/kg /h of proteins, maintaining the same frequency of ingestion, therefore every 15-30 minutes during the first 4-5 hours of post-exercise.
The two phases: molecular mechanisms
The biphasicity is consequence, in both phases, of an increase in:
However, the molecular mechanisms underlying these changes are different.
In the first phase, the increase in glucose transport rate, independent from insulin presence, is mediated by the translocation, induced by the contraction, of glucose transporters, called GLUT4, on the cytoplasmatic membrane of the muscle cell.
In addition, the low glycogen levels also stimulate glucose transport as it is believed that a large portion of transporter-containing vesicles are bound to glycogen, and therefore they may become available when its levels are depleted.
Finally, the low muscle glycogen levels stimulate glycogen synthase activity too: it has been demonstrated that these levels are a regulator of enzyme activity far more potent than insulin.
In the second phase, the increase in muscle glycogen synthesis is due to insulin action on glucose transporters and on glycogen synthase activity of muscle cell. This sensibility to the action of circulating insulin, that can persist up to 48 hours, depending on carbohydrate intake and the amount of resynthesized muscle glycogen, has attracted much attention: it is in fact possible, through appropriate nutritional intervention, to increase the secretion in order to improve glycogen synthesis itself, but also protein anabolism, reducing at the same time the protein-breakdown rate.
Glycogen synthesis rate and insulin
The coingestion of carbohydrates and proteins (or free amino acids) increases postprandial insulin secretion compared to carbohydrates alone (in some studies there was an increase in hormone secretion 2-3 times higher compared to carbohydrates alone).
It was speculated that, thanks to the higher circulating insulin concentrations, further increases in post-exercise glycogen synthesis rate could be obtained compared to those observed with carbohydrates alone, but in reality it does not seem so. In fact, if carbohydrate intake is increased to 1.2 g/kg/h plus 0.4 g/kg/h of proteins no further increases in glycogen synthesis rate are observed if compared to those obtained with the ingestion of carbohydrates alone in the same amount (1,2 g/kg/h, that, as mentioned above, like the coingestion of 0,8 g/kg/h of carbohydrates and 0,4 g/kg/h of proteins, allows to attain the maximum achievable rate in post-exercise) or in isoenergetic quantities, that is, 1.6 g/kg (proteins and carbohydrates contain the same calorie/g)
Insulin and preferential carbohydrate storage
The greater circulating insulin levels reached with the coingestion of carbohydrates and proteins (or free amino acids) might stimulate the accumulation of ingested carbohydrates in tissues most sensitive to its action, such as liver and previously worked muscle, thus resulting in a more efficient storage, for the purposes of sport activity, of the same carbohydrates.
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Biochemistry, Metabolism, and Nutrition