Hormonal Regulation of Glycolysis

HORMONAL REGULATION OF GLYCOLYSIS

The regulation of glycolysis by allosteric activation or inhibition, or the covalent phosphorylation/dephosphorylation of rate-limiting enzymes, is short-term (that is, they influence glucose consumption over periods of minutes or hours). Superimposed on these moment-to-moment effects are slower, and often more profound, hormonal influences on gene expression, or the amount of enzyme protein synthesized. These effects can result in 10-fold to 20-fold increases in enzyme activity that typically occur over hours to days. Although the current focus is on glycolysis, reciprocal changes occur in the rate-limiting enzymes of gluconeogenesis, which are described in Chapter 10. Regular consumption of meals rich in carbohydrate or administration of insulin initiates an increase in the amount of glucokinase , phosphofructokinase, and PK in the liver (Figure 8.23). These changes reflect an increase in gene transcription, resulting in increased enzyme synthesis. High activity of these three enzymes favors the conversion of glucose to pyruvate, a characteristic of the absorptive state. Conversely, gene transcription and synthesis of glucokinase, phosphofructokinase, and PK are decreased when plasma glucagon is high and insulin is low (for example, as seen in fasting or diabetes).

Figure 8.23 Effect of insulin and glucagon on the synthesis of key enzymes of glycolysis in liver. P = phosphate.