Substrate Activation and Product Inhibition of LDH Activity in Human Skeletal Muscle

Abstract Substrate activation and product inhibition have been studied on LDH activity in both directions in human skeletal muscle. K m for the forward and backward reactions for pyruvate and lactate were found to be 0.8 × 10 ‐4 and 0.9 times 10 ‐2 M, respectively. For increases in concentrations of NAD and NADH the LDH activity was found to increase curvilinearly and no K m value could be obtained. Inhibition of the LDH activity corresponding to 50 % of V max was obtained for the forward reaction with a lactate concentration equal to 0.3 × 10 ‐2 M and for the backward reaction (pyruvate) the corresponding value was 1.0 X10 ‐4 M. With concentrations of lactate and pyruvate approximately corresponding to maximal values observed in skeletal muscle with exercise, the inhibition of LDH activity in both directions was equal to or more than 70 % of V max . It is concluded that in an in vitro system concentrations of lactate and pyruvate similar to what are observed under physiological conditions in human skeletal muscles will induce a significant product inhibition on LDH activity obtained from human skeletal muscles in both reaction directions. It seems reasonable to assume that the present in vitro findings might reflect functions operating in an in situ system. Thus it is possible that the products of the LDH catalysed reactions (lactate or pyruvate) might have a regulatory effect on the anaerobic glycolysis as well as the oxidation of lactate in human skeletal muscle.