Inhibition of gluconeogenesis by α-oxo acids

Abstract

DL-Methionine inhibited the synthesis of glucose from lactate and fumarate in rat-kidney-cortex slices. The inhibitory agent proved to be the [alpha]-oxo acid corresponding to methionine ( [gamma] -methylthio-[alpha]-oxobutyrate) formed by D-amino acid oxidase. Marked inhibitions were found with the [alpha]-oxo acids corresponding to phenylalanine and tyrosine. No inhibition occurred in the presence of [alpha]-oxobutyrate, [beta]-methyl-[alpha]-oxobutyrate, [alpha]-oxo-pentanoate and [alpha]-oxohexanoate. Concentrations of [alpha]-oxo acids which strongly inhibited gluconeogenesis (0.2-4 m[image]) had no major effect on the rate of the O uptake. Phenyl-lactate, phenylacetate, cinnamate, benzoate and salicylate (all at 1 m[image]) also inhibited gluconeogenesis from lactate without affecting respiration. L-Phenylalanine had no effect at 10 m[image]. The [alpha]-oxo acids corresponding to glutamate, aspartate, alanine, valine, isoleucine, threonine and norleucine formed glucose in rat-kidney-cortex slices, as expected from the known glucogenic action of the parent amino acids. D-Valine, D-isoleucine and D-alanine formed glucose in kidney-cortex slices whereas the L-forms did not. These differences are presumed to be due to differences in the rate of the conversion of the D-and L-amino acids into the [alpha]-oxo acids.