3-mercaptopicolinic acid and energy metabolism in the liver fluke, Fasciola hepatica

Abstract

Mercaptopicolinic acid inhibited 14CO2 uptake and phosphoenolpyruvate carboxykinase activity in intact fluke. Studies with enzyme preparations showed that the inhibition was mixed-competitive with phosphoenolpyruvate and non-competitive with GTP. Inhibition was not reversed by Mn2+. Pyruvate kinase was not inhibited by mercaptopicolinic acid, although under certain circumstances, mercaptopicolinic acid interfered with the pyruvate kinase assay system. Intact flukes incubated with mercaptopicolinic acid showed depressed adenylate energy charge, increased lactic acid production and reduced flow of carbon from phosphoenolpyruvate to the mitochondrial substrate, malate. Additions of glutamate, alanine or aspartate did not reverse these effects even though, in each case, the amino acid was metabolised and considerably more acid end products were formed than in the absence of mercaptopicolinic acid. The changes in the concentrations of metabolites and end products are consistent with the view that, in flukes whose energy metabolism is impaired by mercaptopicolinic acid, pyruvate enters the mitochondrion and is converted to acetic and propionic acids. Show more