Substrate and product inhibition of rabbit muscle lactic dehydrogenase heart (H4) and muscle (M4) isozymes.

1. Kinetic data concerning the substrate and product inhibition by pyruvate and L-lactate have been obtained with the Md and Hd fractions separated from crystalline rabbit muscle lactic dehydrogenase. 2. The studies indicate that the product inhibition by L-lactate or by pyruvate is predominantly noncompetitive for both the Mq and Hq isozymes. Ki values for product inhibition by L-lactate were 130 mM for the Mh isozyme and 26.0 mM for the H4 isozyme. Ki values for product inhibition by pyruvate were 0.28 mM for the Md isozyme and 0.18 mM for the Hk isozyme. 3. At the concentrations of pyruvate and L-lactate reported by others in contracting muscle, substrate inhibition does not occur to any significant extent under our experimental conditions. However, there is a marked difference in the extent of product inhibition by L-lactate of pyruvate reduction for the two isozymes, but very little difference in the product inhibition by pyruvate of L-lactate oxidation.