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 126.96.36.199), and debranching enzyme (EC 188.8.131.52) 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 184.108.40.206), 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 220.127.116.11) 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.
Nelson D.L., Cox M.M. Lehninger. Principles of biochemistry. 6th Edition. W.H. Freeman and Company, 2012
Stipanuk M.H., Caudill M.A. Biochemical, physiological, and molecular aspects of human nutrition. 3rd Edition. Elsevier health sciences, 2013 [Google eBooks]
Voet D. and Voet J.D. Biochemistry. 4th Edition. John Wiley J. & Sons, Inc. 2011
The Cori cycle, or glucose-lactate cycle, was discovered by Carl Ferdinand Cori and Gerty Theresa Radnitz, a husband-and-wife team, in the ‘30s and ‘40s of the last century . They demonstrated the existence of a metabolic cooperation between the skeletal muscle working under low oxygen conditions and the liver. This cycle can be summarized as follows:
the conversion of glucose to lactic acid, or lactate, by anaerobic glycolysis in skeletal muscle cells;
the diffusion of lactate from muscle cells into the bloodstream, by which it is transported to the liver;
In addition to skeletal muscle, this metabolic cooperation was also demonstrated between other extrahepatic tissues and liver. Indeed, like the glucose-alanine cycle, the glucose-lactate cycle is active between the liver and all those tissues that do not completely oxidize glucose to CO2 and H2O, in which case pyruvate for conversion to lactate or, by transamination, to alanine would lack (see below).
In addition to skeletal muscle cells, examples of cells that continually produce lactic acid are red blood cells, immune cells in the lymph nodules, proliferating cells in the bone marrow, and epithelial cells in the skin.
Notice that skeletal muscle produces lactate even at rest, although at low rate.
From a biochemical point of view, the Cori cycle links gluconeogenesis with anaerobic glycolysis, using different tissues to compartmentalize opposing metabolic pathways. In fact, in the same cell, regardless of the cell type, these metabolic pathways are not very active simultaneously. Glycolysis is more active when the cell requires ATP; by contrast, when the demand for ATP is low, gluconeogenesis, in those cells where it occurs, is more active.
And it is noteworthy that, although traditionally the metabolic pathways, such as glycolysis, citric acid cycle, or gluconeogenesis, are considered to be confined within individual cells, the Cori cycle, as well as the glucose-alanine cycle, occurs between different cell types.
Finally, it should be underscored that the Cori cycle also involves the renal cortex, particularly the proximal tubules, another site where gluconeogenesis occurs.
The steps of the Cori cycle
The analysis of the steps of the Cori cycle is made considering the lactate produced by red blood cells and skeletal muscle cells. Mature red blood cells are devoid of mitochondria, nucleus and ribosomes, and obtain the necessary energy only by glycolysis. The availability of NAD+ is essential for glycolysis to proceed as well as for its rate: the oxidized form of the coenzyme is required for the oxidation of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate in the reaction catalyzed by glyceraldehyde 3-phosphate dehydrogenase (EC 18.104.22.168).
The accumulation of NADH is avoided by the reduction of pyruvate to lactate, in the reaction catalyzed by lactate dehydrogenase (EC 22.214.171.124), where NADH acts as reducing agent.
Pyruvate + NADH + H+ → Lactate + NAD+
The skeletal muscle, particularly fast-twitch fibers which contain a reduced number of mitochondria, under low oxygen condition, such as during intense exercise, produces significant amounts of lactate. In fact, in such conditions:
the rate of pyruvate production by glycolysis exceeds the rate of its oxidation by the citric acid cycle, so that less than 10% of the pyruvate enters the citric acid cycle;
the rate at which oxygen is taken up by the cells is not sufficient to allow aerobic oxidation of all the NADH produced.
And, like in red blood cells, the reaction catalyzed by lactate dehydrogenase, regenerating NAD+, allows glycolysis to proceed.
However, lactate is an end product of metabolism that must be converted back into pyruvate to be used.
The plasma membrane of most cells is freely permeable to both pyruvate and lactate that can thus reach the bloodstream. And, regarding for example the skeletal muscle, the amount of lactate that leaves the cell is greater than that of pyruvate due to the high NADH/NAD+ ratio in the cytosol and to the catalytic properties of the skeletal muscle isoenzyme of LDH.
Once into the bloodstream, lactate reaches the liver, which is its major user, where it is oxidized to pyruvate in the reaction catalyzed by the liver isoenzyme of lactate dehydrogenase.
Lactate + NAD+ → Pyruvate + NADH + H+
In the hepatocyte, this oxidation is favored by the low NADH/NAD+ ratio in the cytosol.
Then, pyruvate enters the gluconeogenesis pathway to be converted into glucose.
Glucose leaves the liver, enters into the bloodstream and is delivered to the muscle, as well as to other tissues and cells that require it, such as red blood cells and neurons, thus closing the cycle.
The enzyme is a tetramer composed of two different types of subunits, designed as:
H subunit (heart) or B chain;
M subunit (muscle) or A chain.
The H subunit predominates in the heart, whereas the M subunit predominates in the skeletal muscle and liver. Typically, tissues in which a predominantly or exclusively aerobic metabolism occurs, such as the heart, synthesize H subunits to a greater extent than M subunits, whereas tissues in which anaerobic metabolism is important, such as skeletal muscle, synthesize M subunits to a greater extent than H subunits.
The two subunits associate in 5 different ways to form homopolymers, that is, macromolecules formed by repeated, identical subunits, or heteropolymers, that is, macromolecules formed by different subunits. Different LDH isoenzymes have different catalytic properties, as well as different distribution in various tissues, as indicated below:
H4, also called type 1, LDH1, or A4, a homopolymer of H subunits, is found in cardiac muscle, kidney, and red blood cells;
H3M1, also called type 2, LDH2, or A3B, has a tissue distribution similar to that of LDH1;
H2M2, also called type 3, LDH3, or A2B2, is found in the spleen, brain, white cells, kidney, and lung;
H1M3, also called type 4, LDH4, or AB3, is found in the spleen, lung, skeletal muscle, lung, red blood cells, and kidney;
M4, also called type 5, LDH5, or B4, a homopolymer of M subunits, is found in the liver, skeletal muscle, and spleen.
The H4 isoenzyme has a higher substrate affinity than the M4 isoenzyme.
The H4 isoenzyme is allosterically inhibited by high levels of pyruvate (its product), whereas the M4 isoenzyme is not.
The other LDH isoenzymes have intermediate properties, depending on the ratio between the two types of subunits.
It is thought that the H4 isoenzyme is the most suitable for catalyzing the oxidation of lactate to pyruvate that, in the heart, due to its exclusively aerobic metabolism, is then completely oxidized to CO2 and H2O. Instead, the M4 isoenzyme is the main isoenzyme found in skeletal muscle, most suitable for catalyzing the reduction of pyruvate to lactate, thus allowing glycolysis to proceed in anaerobic conditions.
Other metabolic fates of lactate
From the above, it is clear that lactate is not a metabolic dead end, a waste product of glucose metabolism.
And it may have a different fate from that entering the Cori cycle.
For example, in skeletal muscle during recovery following an exhaustive exercise, that is, when oxygen is again available, or if the exercise is of low intensity, lactate is re-oxidized to pyruvate, due to NAD+ availability, and then completely oxidized to CO2 and H20, with a greater production of ATP than in anaerobic condition. In such conditions, the energy stored in NADH will be released, yielding on average 2.5 ATP per molecule of NADH.
In addition, lactate can be taken up by exclusively aerobic tissues, such as heart, to be oxidized to CO2 and H20.
Energy cost of the glucose-lactate cycle
The Cori cycle results in a net consumption of 4 ATP.
The gluconeogenic leg of the cycle consumes 2 GTP and 4 ATP per molecule of glucose synthesized, that is, 6 ATP.
The ATP-consuming reactions are catalyzed by:
Since two molecules of lactate are required for the synthesis of one molecule of glucose, the net cost is 2 x 3 = 6 high energy bonds per molecule of glucose.
Conversely, the glycolytic leg of the cycle produces only 2 ATP per molecule of glucose.
Therefore, more energy is required to produce glucose from lactate than that obtained by anaerobic glycolysis in extrahepatic tissues. This explains why the Cori cycle cannot be sustained indefinitely.
Is the Cori cycle a futile cycle?
The continuous breakdown and resynthesis of glucose, feature of the Cori cycle, might seem like a waste of energy. Indeed, this cycle allows the effective functioning of many extrahepatic cells at the expense of the liver and partly of the renal cortex. Below, two examples.
Red blood cells
These cells, lacking a nucleus, ribosomes, and mitochondria, are smaller than most other cells. Their small size allows them to pass through tiny capillaries. However, the lack of mitochondria makes them completely dependent on anaerobic glycolysis for ATP production. Then, the lactate is partly disposed of by the liver and renal cortex.
Its cells, and particularly fast-twitch fibers contracting under low oxygen conditions, such as during intense exercise, produce much lactate.
In such conditions, anaerobic glycolysis leads to the production of 2 ATP per molecule of glucose, 3 if the glucose comes from muscle glycogen, therefore, much lower than the 29-30 ATP produced by the complete oxidation of the monosaccharide. However, the rate of ATP production by anaerobic glycolysis is greater than that produced by the complete oxidation of glucose. Therefore, to meet the energy requirements of contracting muscle, anaerobic glycolysis is an effective means of ATP production. But this could lead to an intracellular accumulation of lactate, and a consequent reduction in intracellular pH. Obviously, such accumulation does not occur, due also to the Cori cycle, in which the liver pays the cost of the disposal of a large part of the muscle lactate, thereby allowing the muscle to use ATP for the contraction.
And the oxygen debt, which always occurs after a strenuous exercise, is largely due to the increased oxygen demand of the hepatocytes, in which the oxidation of fatty acids, their main fuel, provides the ATP required for gluconeogenesis from lactate.
During trauma, sepsis, burns, or after major surgery, an intense cell proliferation occurs in the wound, that is a hypoxic tissue, and in bone marrow. This in turn results in greater production of lactate, an increase in the flux through the Cori cycle and an increase in ATP consumption in the liver, which, as previously said, is supported by an increase in fatty acid oxidation. Hence, the nutrition plan provided to these patients must be taken into account this increase in energy consumption.
A similar condition seems to occur also in cancer patients with progressive weight loss.
The Cori cycle is also important during overnight fasting and starvation.
The Cori cycle and glucose-alanine cycle
These cycles are metabolic pathways that contribute to ensure a continuous delivery of glucose to tissues for which the monosaccharide is the primary source of energy.
The main difference between the two cycles consists in the three carbon intermediate which is recycled: in the Cori cycle, carbon returns to the liver in the form of pyruvate, whereas in the glucose-alanine cycle in the form of alanine.
For more information, see: glucose-alanine cycle.
Bender D.A. Introduction to nutrition and metabolism. 3rd Edition. Taylor & Francis, 2004
Berg J.M., Tymoczko J.L., and Stryer L. Biochemistry. 5th Edition. W. H. Freeman and Company, 2002
One of the main functions of the liver is to participate in the maintaining of blood glucose levels within well defined range (in the healthy state before meals 60-100 mg/dL or 3.33-5.56 mmol/L). To do it the liver releases glucose into the bloodstream in:
during physical activity.
Blood glucose levels and role of hepatic glucose-6-phosphatase
In the liver, glycogen is the storage form of glucose which is released from the molecule not as such, but in the phosphorylated form i.e. with charge, the glucose-1-phosphate (this process is called glycogenolysis). The phosphorylated molecule can’t freely diffuse from the cell, but in the liver it is present the enzyme glucose-6-phosphatase that hydrolyzes glucose-6-phosphate, produced from glucose-1-phosphate in the reaction catalyzed by phosphoglucomutase, to glucose (an irreversible dephosphorylation).
Then, glucose can diffuse from the hepatocyte, via a transporter into the plasma membrane called GLUT2, into the bloodstream to be delivered to extra-hepatic cells, in primis neurons and red blood cells for which it is the main, and for red blood cells the only energy source (neurons, with the exception of those in some brain areas that can use only glucose as energy source, can derive energy from another source, the ketone bodies, which becomes predominant during periods of prolonged fasting).
Note: the liver obtains most of the energy required from the oxidation of fatty acids , not from glucose.
Glucose-6-phosphatase is present also in the kidney and gut but not in the muscle and brain; therefore in these tissues glucose-6-phosphate can’t be released from the cell.
Glucose-6-phosphatase plays an important role also in gluconeogenesis.
Glucose-6-phosphatase is present into the membrane of endoplasmic reticulum and the hydrolysis of glucose-6-phosphate occurs into its lumen (therefore this reaction is separated from the process of glycolysis). The presence of a specific transporter, the glucose-6-phosphate translocase, is required to transport the phosphorylated molecule from citosol into the lumen of endoplasmic reticulum. Although a glucose transporter is present into the membrane of endoplasmic reticulum, most of the released glucose is not transported back into the cytosol of the cell but is secreted into the bloodstream. Finally, an ion transporter transports back into the cytosol the inorganic phosphate released into the endoplasmic reticulum.
Arienti G. “Le basi molecolari della nutrizione”. Seconda edizione. Piccin, 2003
Cozzani I. and Dainese E. “Biochimica degli alimenti e della nutrizione”. Piccin Editore, 2006
Giampietro M. “L’alimentazione per l’esercizio fisico e lo sport”. Il Pensiero Scientifico Editore, 2005
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.
Arienti G. “Le basi molecolari della nutrizione”. Seconda edizione. Piccin, 2003
Cozzani I. and Dainese E. “Biochimica degli alimenti e della nutrizione”. Piccin Editore, 2006
Giampietro M. “L’alimentazione per l’esercizio fisico e lo sport”. Il Pensiero Scientifico Editore, 2005
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.
Beelen M., Burke L.M., Gibala M.J., van Loon J.C. Nutritional strategies to promote postexercise recovery. Int J Sport Nutr Exerc Metab 2010:20(6);515-32 doi:10.1123/ijsnem.20.6.515
Berardi J.M., Noreen E.E., Lemon P.W.R. Recovery from a cycling time trial is enhanced with carbohydrate-protein supplementation vs. isoenergetic carbohydrate supplementation. J Intern Soc Sports Nutrition 2008;5:24 doi:10.1186/1550-2783-5-24
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Invert sugar (also known as inverted sugar) is sucrose partially or totally cleaved into fructose and glucose (also known dextrose) and, apart from the chemical process used (see below), the obtained solution has the same amount of the two monosaccharides.
Moreover, according to the product, not cleaved sucrose may also be present.
Invert sugar production
The breakdown of sucrose may happen in a reaction catalyzed by enzymes, such as:
sucrase, active at our own intestinal level;
invertase, an enzyme secreted by honeybees into the honey and used industrially to obtain invert sugar.
Another process applies acid action, as it happens partly in our own stomach and as it happened in the old times, and still happens, at home-made and industrial level. Sulfuric and hydrochloric acids was used, heating the solution with caution for some time; in fact the reaction is as fast as the solution is acid, regardless of the type of acid used, and as higher the temperature is. The acidity is then reduced or neutralized with alkaline substances, as soda or sodium bicarbonate.
A chemical process as described occurs when acid foods are prepared; i.e. in the preparation of jams and marmalades, where both conditions of acidity, naturally, and high temperatures, by heating, are present. The situation is analogous when fruit juices are sweetened with sucrose.
The reaction develops at room temperature as well, obviously more slowly.
What is the practical outcome of that?
It means that, during storage, also sweets and acid foods, even those just seen, go towards a slow reaction of inversion of contained/residue sucrose, with consequent modification of the sweetness, since invert sugar at low temperatures is sweeter (due to the presence of fructose), and assumption of a different taste profile.
Properties and uses
It is principally utilized in confectionery and ice-cream industries thanks to some peculiar characteristics.
It has an higher affinity for water (hydrophilicity) than sucrose (see fructose) therefore it keeps food more humid: e.g. cakes made with invert sugar dry up less easily.
It avoids or slows down crystal formation (dextrose and fructose form less crystals than sucrose), property useful in confectionery industries for icings and coverage.
It has a lower freezing point.
It increases, just a bit, the sweetness of the product in which it has been added, as it is sweeter than an equal amount of sucrose (the sweetness of fructose depends on the temperature in which it is present).
It may take part to Maillard reaction (sucrose can’t do it) thus contributing to the color and taste of several bakery products.
It should be noted that honey, lacking in sucrose, has almost the same composition in fructose and glucose of the 100% invert sugar (fructose is slightly more abundant than glucose). So, diluted honey, better if not much aromatic, may replace industrial invert sugar.
Belitz .H.-D., Grosch W., Schieberle P. “Food Chemistry” 4th ed. Springer, 2009
Bender D.A. “Benders’ Dictionary of Nutrition and Food Technology”. 8th Edition. Woodhead Publishing. Oxford, 2006