8 Glycogen metabolism
8.1 Glycogen synthesis
8.2 Glycogen degradation
8.3 Glycogen storage diseases
8.4 Regulation of glycogen metabolism
Glycogen is a polymeric storage form of glucose (Figure 8-1). It is very similar to amylopectin, the branched polyglucose molecule found in starch (Figure 1.5.2-1); the only difference is that glycogen is more highly branched. It is synthesized from glucose in times of plenty, i.e. after a meal rich in carbohydrates, and converted back to glucose when the later is in demand. It is found in many tissues, but only two of these are quantitatively important:
- The liver stores glycogen for the purpose of releasing the glucose contained in it into the circulation; glycogen stored here therefore serves the entire organism. The glycogen content of a fully stocked liver amounts to as much as 10% of its wet weight, i.e. about 150-200 grams. Since glycogen is so similar in structure to starch, this is comparable to 200 grams of dry spaghetti.
- According to the books, the skeletal muscle stores glycogen only for
'selfish' reasons. Glucose released from glycogen in the muscle is not
released into the blood but consumed then and there. The concentration in
muscle tissue is lower than in the liver, but because of the large mass
of sceletal muscle the amount of glycogen stored in muscle is actually
about twice that found in the liver.
The alleged inability of skeletal muscle to release glucose would result from a lack of the enzyme glucose-6-phosphatase, without which free glucose cannot be obtained from glycogen. However, recent work has shown that this enzyme is indeed expressed at appreciable levels in the muscle also1. This raises the interesting possibility that contrary to traditional belief skeletal muscle does function as a reservoir of glucose. Of course, an accurate understanding of blood glucose regulation and homeostasis is essential in the treatment of diabetes mellitus.
Why do organisms store glucose in polymeric rather than in free form? Free glucose would cause an inacceptably high osmotic pressure inside the cell. The osmotic pressure associated with a solute follows the gas equation:
pV = nRT ⇔ p = n/V × RT
This means that the osmotic pressure is proportional to the number of molecules per volume, or the molar concentration. Consider the amount of glycogen stored in the liver: 10% equals 100g per liter. Considering that each glucose residue in glycogen has a molar weight of 162 Da, this amounts to roughly 0.6 moles/l. This is approximately twice as high as the total concentration of small solutes inside the liver cell. Therefore, if all the glycogen were converted to glucose, the osmotic pressure would triple, and the liver cell would suck water like a delirious camel and burst. Thus, polymerization of glucose makes storage of large amounts of glucose 'bio-compatible'.
1: Shee et al., J. Biol. Chem. 279:26215-9 (2004) and references cited therein