Glycogen utilization

In the fasting state, glycogen is broken down by the removal of glucose units one at a time from the many ends of the molecule. As shown in Figure 5.9, the reaction is a phosphorolysis - cleavage of the glycoside link between two glucose molecules by the introduction of phosphate. The product is glucose 1-phosphate, which is then isomerized to glucose 6-phosphate. In the liver glucose 6-phosphatase catalyses the hydrolysis of glucose 6-phosphate to free glucose, which is exported for use especially by the brain and red blood cells.

Muscle cannot release free glucose from the breakdown of glycogen, because it lacks glucose 6-phosphatase. However, muscle glycogen can be an indirect source of blood glucose in the fasting state. Glucose 6-phosphate from muscle glycogen undergoes glycolysis to pyruvate (see Figure 5.10), which is then transaminated to alanine. Alanine is exported from muscle and taken up by the liver for use as a substrate for gluconeogenesis (section 5.7).

Glycogen phosphorylase stops cleaving a1^4 links four glucose residues from a branch point, and a debranching enzyme catalyses the transfer of a three glucosyl unit from one chain to the free end of another chain. The a 1^6 link is then hydrolysed by a glucosidase, releasing glucose.

The branched structure of glycogen means that there are a great many points at which glycogen phosphorylase can act; in response to stimulation by adrenaline (section 10.3) there can be a very rapid release of glucose 1-phosphate from glycogen.

Endurance athletes require a slow release of glucose 1-phosphate from glycogen over a period of hours, rather than a rapid release. There is some evidence that this is achieved better from glycogen that is less branched, and therefore has fewer points at which glycogen phosphorylase can act. The formation of branch points in glycogen synthesis is slower than the formation of a 1^4 links, and this has been exploited in the process of 'carbohydrate loading' in preparation for endurance athletic events. The athlete exercises to exhaustion, when muscle glycogen is more or less completely depleted, then consumes a high-carbohydrate meal, which stimulates rapid synthesis of glycogen with fewer branch points than normal. There is little evidence to show whether or not this improves endurance performance; such improvement as has been reported may be the result of knowing that one has made an effort to improve performance rather than any real metabolic effect.

Because the brain is largely dependent on glucose as its metabolic fuel (and red blood cells are entirely so) there is a need to maintain the blood concentration of glucose between about 3 and 5 mmol/L in the fasting state. If the plasma concentration of glucose falls below about 2 mmol/L there is a loss of consciousness - hypoglycaemic coma.

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