Inhibition of glutamic-pyruvic transaminase by DL-cycloserine and other compounds

Summary

The author studied changes in glutamic-pyruvic transaminase activity of liver homogenates under the effect of various compounds capable and incapable of forming Schiff bases with phosphopyridoxal.

The following compounds proved effective in inhibiting the glutamic-pyruvic transaminase activity in the homogenates of rat liver: 1) acyclic-containing both amino and hydroxyamino groups, or hydroxyamino group alone (β-aminohydroxyalanine and γ-aminohydroxybutyric acid and their ethyl esters); 2) cyclic-differing from cycloserine by the absence of a free amino group (N-methylcycloserine and isoxazolidone-3); 3) hydroxamic acids (hydroxamic acid of α-alanine and β-chlorpropionhydroxamic acid). All these compounds, except for the ethyl ester of β-aminohydroxyalanine, the efficacy of which equals that of cycloserine, are less effective than cycloserine; their efficacy, however, is greater than that of isoniazide. Possible mechanisms of action of the above inhibitors are discussed.