Tag Archives: glycogen synthesis

Glycogen: an efficient storage form of energy in aerobic conditions

What is the net energy yield for the oxidation of a glucose unit from glycogen in aerobic conditions?

Aerobic Conditions: Glycogen Structure
Fig. 1 – Glycogen Structure

In aerobic conditions, the oxidation of a free glucose to CO2 and H2O (glycolysis, Krebs cycle and oxidative phosphorylation) leads to the net production of about 30 molecules of ATP.

Glucose from the action of glycogen phosphorylase: glucose-1-phosphate release (about 90% of the removed units).

Glycogen synthesis from free glucose costs two ATP units for each molecule; a glucose-1-phosphate is released by the action of glycogen phosphorylase with recovering/saving one of the two previous ATP molecules.
Therefore in aerobic condition, the oxidation of glucose starting from glucose-6-phosphate and not from free glucose yields 31 ATP molecules and not 30 (one ATP instead of two is expended in the activation phase, 30 ATP are produced during Krebs cycle and oxidative phosphorylation: 31 ATP gained).
The net rate between cost and yield is 1/31 (an energy conservation 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

If we combine glycogen synthesis, glycogen breakdown and finally the oxidation of glucose to CO2 and H2O we obtain 30 molecules of ATP per stored glucose unit, that is the overall reaction is:

glucose + 29 ADP + 30 Pi → 29 ATP + 6 CO2 + 6 H2O

Glucose from the action of debranching enzyme: free glucose release (about 10% of the removed units).

The net yield in ATP between glycogen synthesis and breakdown is two ATP molecules expended because of free glucose is released.
In this case the oxidation of glucose starts from the not-prephosphorylated molecule so we obtain 30 ATP molecules.
The net rate between cost and yield is 2/30 (a energy conservation of about 93,3%).
Considering the oxidation of the glucose units from glycogen to CO2 and H2O we have an energy conservation of:

1-(((1/31)*0,9)+((2/30)*0,1))=0,9643

Conclusion

In aerobic conditions, there is the conservation of about 97% of energy into the glycogen molecule, an extremely efficient storage form of energy.

References

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

Mahan LK, Escott-Stump S.: “Krause’s foods, nutrition, and diet therapy” 10th ed. 2000

Mariani Costantini A., Cannella C., Tomassi G. “Fondamenti di nutrizione umana”. 1th ed. Il Pensiero Scientifico Editore, 1999

Nelson D.L., M. M. Cox M.M. Lehninger. Principles of biochemistry. 4th Edition. W.H. Freeman and Company, 2004

Stipanuk M.H.. “Biochemical and physiological aspects of human nutrition” W.B. Saunders Company-An imprint of Elsevier Science, 2000

Ingestion of solid, liquid or gel carbohydrates 60 min before exercise

Liquid Carbohydrate Ingestion
Fig. 1 – Liquid Carbohydrate Ingestion

The form of carbohydrates ingested before exercise may have different effects on both metabolism and performance. Moreover, the ingestion of solid foods slows gastric empty, digestion and absorption rates compared with liquid foods and this has a different impact on glycemia.
For these reasons, several studies have investigated the effects of the form of carbohydrates on glycemic responses, oxidation rates and performance.

  • Studies comparing solid versus liquid carbohydrates and solid versus gel carbohydrates have found no difference in glycemic responses between groups.
  • Studies that have investigated difference in performance effects have found no differences.
  • Furthermore, no differences are found in carbohydrate oxidation rates between the carbohydrate ingestion in the three forms during exercise.

Therefore, it seems not to be the form of ingested carbohydrates that can enhance or reduce performance (in addition, even glycogen synthesis doesn’t vary; study conducted with liquid or solid carbohydrates).

Conclusion

It is advisable that athlete ingests whichever form of carbohydrates best suits, based on his experience and cost-effectiveness of the product.

References

Glycogen: an efficient storage form of energy in anaerobic conditions

What is the net energy yield for the oxidation of a glucose unit from glycogen in anaerobic conditions?

In anaerobic conditions, the oxidation of a free glucose to lactate leads to the net production of two molecules of ATP.

Anaerobic Conditions: Glycolysis to Lactate
Fig. 1 – Glycolysis to Lactate

Glucose from the action of glycogen phosphorylase: glucose-1-phosphate release (about 90% of the removed units).

Glycogen synthesis from free glucose costs two ATP units for each molecule; a glucose-1-phosphate is released by the action of glycogen phosphorylase, with recovering/saving of one of the two previous ATP molecules.
Therefore the oxidation of glucose to lactate starting from glucose-6-phosphate and not from free glucose yields three ATP molecules and not two (one ATP is expended in the activation stage instead of two, 4 ATP are produced in the third stage: three ATP gained).
The net rate between cost and yield is 1/3 (an energy conservation 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

If we combine glycogen synthesis, glycogen breakdown and finally glycolysis to lactate we obtain only one ATP molecule per stored glucose unit, that is the overall sum is:

glucose + ADP + Pi → 2 lactate + ATP

Glucose from the action of debranching enzyme: free glucose release (about 10% of the removed units).

The net yield in ATP between glycogen synthesis and breakdown is two ATP molecules expended because of free glucose is released.
In this case the oxidation of glucose starts from the not-prephosphorylated molecule and it yields two ATP molecules.
Therefore the net yield in ATP is zero.
Considering the oxidation of the glucose units from glycogen to lactate we have an energy conservation of:

1-(((1/3)*0,9)+((2/2)*0,1))=0,60

Conclusion

In anaerobic conditions, there is the conservation of about 60% of energy into the glycogen molecule, a good storage form of energy.

References

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

Mahan LK, Escott-Stump S.: “Krause’s foods, nutrition, and diet therapy” 10th ed. 2000

Mariani Costantini A., Cannella C., Tomassi G. “Fondamenti di nutrizione umana”. 1th ed. Il Pensiero Scientifico Editore, 1999

Nelson D.L., M. M. Cox M.M. Lehninger. Principles of biochemistry. 4th Edition. W.H. Freeman and Company, 2004

Stipanuk M.H.. “Biochemical and physiological aspects of human nutrition” W.B. Saunders Company-An imprint of Elsevier Science, 2000

Strategies to maximize muscle glycogen resynthesis after exercise

Post-exercise muscle glycogen synthesis

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 glycogen to 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.

Muscle glycogen synthesis after exercise: the first phase

Muscle Glycogen
Fig. 1 – Glycogen Structure

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.

Muscle glycogen synthesis after exercise: 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 of muscle glycogen synthesis: molecular mechanisms

The biphasicity is consequence, in both phases, of an increase in:

  • glucose transport rate into cell;
  • the activity of glycogen synthase, the enzyme that catalyzes glycogen synthesis.

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 (H4)

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.

References

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 [Abstract]

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 [PDF]

Betts J., Williams C., Duffy K., Gunner F. The influence of carbohydrate and protein ingestion during recovery from prolonged exercise on subsequent endurance performance. J Sports Sciences 2007;25(13):1449-60 [Abstract]

Howarth K.R., Moreau N.A., Phillips S.M., and Gibala M.J. Coingestion of protein with carbohydrate during recovery from endurance exercise stimulates skeletal muscle protein synthesis in humans. J Appl Physiol 2009:106;1394–1402  [Abstract]

Jentjens R., Jeukendrup A. E. Determinants of post-exercise glycogen synthesis during short-term recovery. Sports Medicine 2003:33(2);117-144 [Abstract]

Millard-Stafford M., Childers W.L., Conger S.A., Kampfer A.J., Rahnert J.A. Recovery nutrition: timing and composition after endurance exercise. Curr Sports Med Rep 2008;7(4):193-201 [Abstract]

Price T.B., Rothman D.L., Taylor R., Avison M.J., Shulman G.I., Shulman R.G. Human muscle glycogen resynthesis after exercise: insulin-dependent and –independent phases. J App Physiol 1994:76(1);104–111 [Abstract]

van Loon L.J.C., Saris W.H.M., Kruijshoop M., Wagenmakers A.J.M. Maximizing postexercise muscle glycogen synthesis: carbohydrate supplementation and the application of amino acid or protein hydrolysate mixtures. Am J Clin Nutr 2000;72: 106-111 [Abstract]