Inhibition of renal gluconeogenesis and phosphoenolpyruvate carboxykinase activity by 3-mercaptopicolinic acid: Studies in rat, guinea pig, dog, rabbit, and man

The inhibition of gluconeogenesis in isolated kidney tubules by 3-mercaptopicolinate, a specific inhibitor of the phosphoenolpyruvate caroboxykinase reaction, is species specific. At any given concentration of the inhibitor, the degree of inhibition is in the order rat>guinea pig≥man>rabbit≥dog. The intracellular distribution of PEPCK activity (as measured in both the forward and backward directions) supports the conclusion that in the intact cell the cytosolic enzyme is preferentially inhibited. Analysis of the inhibition failed to demonstrate any significant differences between the enzymes, regardless of intracellular or animal source. All enzymes exhibited a similar K(i)(2-10 μM) for 3-mercaptopicolinate when assayed in the forward direction. The observed preferential cytosolic inhibition could be due to either in situ differences in metallic ions concentration or a restriction in mitochondrial permeability for mercaptopicolinate.