Carbohydrate metabolism allosteric effects

FIGURE 18.11 Allosteric effects in the control of carbohydrate metabolism. The effect of AMP (0, 10, and 25 aM [micromolar]) on the inhibition of fructose-1,6-fe iphosphatase by fructose-2,6-fe iphosphate. Activity was measured in the presence of 10 pM fructose-1,6-fe sphosphate. (Adapted from Van Schaftingen, E., and H. G. Hers,... 

Ghanges in the availability of substrates are responsible for most changes in metabolism either directly or indirectly acting via changes in hormone secretion. Three mechanisms are responsible for regulating the activity of enzymes in carbohydrate metabolism (1) changes in the rate of enzyme synthesis, (2) covalent modification by reversible phosphorylation, and (3) allosteric effects. 

There are many examples of phosphorylation/dephosphorylation control of enzymes found in carbohydrate, fat and amino acid metabolism and most are ultimately under the control of a hormone induced second messenger usually, cytosolic cyclic AMP (cAMP). PDH is one of the relatively few mitochondrial enzymes to show covalent modification control, but PDH kinase and PDH phosphatase are controlled primarily by allosteric effects of NADH, acetyl-CoA and calcium ions rather than cAMP (see Table 6.6). 

A number of control mechanisms operate in carbohydrate metabolism. They include allosteric effects, covalent modification, substrate cycles, and genetic control. These mechanisms affect key enzymes in different ways with different time responses. 

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