Kinetics, mechanism, and regulation of rat skeletal muscle hexokinase.

نویسندگان

J D Lueck

H J Fromm

چکیده

Initial rate studies were employed to investigate the kinetic mechanism of action of rat skeletal muscle type II hexokinase (EC 3.7.1.1). These investigations involved the use of substrate analogs which act as competitive inhibitors and product inhibition experiments. The findings indicate that substrates n-glucose and MgATP2add randomly to hexokmase. Both products exhibit noncompetitive inhibition relative to either substrate. The kinetic results are compatible with a Random Bi Bi mechanism of either the rapid equilibrium or the steady state type. The kinetic data are qualitatively identical with those obtained for yeast hexokinase. Although muscle hexokinase does not respond as predicted to the model of adenylate energy charge, it is potently inhibited by levels of glucose-6-P and orthophosphate thought to exist in muscle tissue. The enzyme is inhibited 79% at the approximate intracellular concentrations of substrates, products, and phosphate. This inhibition is increased to 96% when the concentration of these compounds rises to those levels believed to exist during tetanic muscular contraction. The data suggest that the muscle type II hexokinase is not functional during periods of highly active glycogenolysis and glycolysis in rat muscle tissue.

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