Glucose-phosphorylating isoenzymes

A good example of allosteric inhibition is given by hexokinase (HK) isoenzymes of muscle. The product of the HK reaction, glucose-6-P allosterically inhibits the enzyme, so matching the phosphorylation of glucose to its overall metabolism, helps to regulate... 

Muscle glycogen phosphorylase is one of the most well studied enzymes and was also one of the first enzymes discovered to be controlled by reversible phosphorylation (by E.G. Krebs and E. Fischer in 1956). Phosphorylase is also controlled allosterically by ATP, AMP, glucose and glucose-6-phosphate. Structurally, muscle glycogen phosphorylase is similar to its hepatic isoenzyme counterpart composed of identical subunits each with a molecular mass of approximately 110 kDa. To achieve full activity, the enzyme requires the binding of one molecule of pyridoxal phosphate, the active form of vitamin B6, to each subunit. 

Hexokinases, the enzymes that catalyze the phosphorylation of glucose, are a family of tissue-specific isoenzymes that differ in their kinetic properties. The isoenzyme found in liver and p cells of the pancreas has a much higher than other hexokinases and is called glucokinase. In many cells, some of the hexokinase is bound to porins in the outer mitochondrial membrane (voltage-dependent anion channels see Chapter 21), which gives these enzymes first access to newly synthesized ATP as it exits the mitochondria. 

A non-phosphorylated form of glycogen phosphorylase B (EC 2.4.1.1) has been isolated from rabbit liver.Co-operative interactions between the substrate-binding sites become more pronounced in the presence of inhibitors, ATP, and D-glucose, and less pronounced in the presence of the activator AMP. Isoenzymes of glycogen phosphorylase and glycogen synthetase are preserved in chick embryo liver and in the liver of adult chicken. The changes which were observed in the ratio between phosphorylases a and b, on the one hand, and glycogen synthetases I and D on the other, do not fit into the Hers scheme for the liver of adult mammals. 

Heart muscle contains a different PFK-2/FBPase-2 isoenzyme, whose phosphorylation activates rather than inhibits PFK-2. Thus any hormone that promotes increased cAMP synthesis also causes an increase in the level of heart muscle F2,6P, leading to an increase in the rates of both glycogenolysis and glycolysis, so that glycogenolysis is followed by glycolysis and not by glucose secretion. 

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