The action of isoniazid on the transaminases of Mycobacterium tuberculosis (B.C.G.).

One of the proposed mechanisms for the action of iwonicotinic acid hydrazide (isoniazid) has been the inhibition of enzyme systems which require pyridoxal phosphate (Cymerman-Craig, Rubbo, Willis & Edgar, 1955). However, it appeared unlikely that the inhibition of an enzyme system present in many bacteria could account for the highly specific activity of isoniazid in low concentrations against species of Mycobacteriurn. Sakai (1954) found that the aspartic-glutamic acid transaminase of Mycobacterium tuberculoswi B.C.G. strain (B.C.G.) was inhibited 90-100% by 0.01m-isoniazid with an isoniazid-sensitive strain, whereas the transaminase of the resistant B.C.G. was not inhibited. Transamination of asparagine, glycine, phenylalanine, leucine, valine, alanine and aspartic acid by avian tubercle bacilli was described by Ito & Sugano (1954), who also observed the inhibition of the reaction by 0.01M-isoniazid. Yonemura & Iisuka (1955) described the transainination of twenty amino acids in the presence of a-oxoglutarate, by a virulent strain of bovine tubercle bacilli. They found no transamination between any amino acid, other than glutamic acid, and pyruvic or oxaloacetic acid. Yamamoto (1955) found that cysteine desulphydrase of sensitive and resistant strains of B.C.G. was inhibited by isoniazid. The inhibition was partially reversed by pyridoxal and adenosine triphosphate. The results with enzymes of Mycobacterium closely parallel those obtained with organisms naturally insensitive to isoniazid, such as E8cherichia coli, with which it was shown that enzymes requiring pyridoxal phosphate were inhibited by isoniazid at concentrations of the order of O01OM (Yoneda, Kato & Okajima, 1952). The experiments described below were made with the aim of determining whether the inhibition of transaminase in Mycobacterium could account for the highly specific action of isoniazid in low concentrations.