Biosynthesis of Porphyrin Precursors

Bovine liver mitochondria have been found to contain an enzyme which will catalyze the formation of &aminolevulinic acid via a transamination reaction rather than via the condensation of glycine and succinyl coenzyme A. The enzyme, L-alanine:y,bdioxovaleric acid aminotransferase (y,&dioxovalerate transaminase) was isolated and purified to apparent homogeneity. y,&Dioxovalerate transaminase is quite stable, has optimal activity at pH 6.9, requires pyridoxal phosphate as a cofactor and has an apparent molecular weight of 240,000. The enzyme has high specificity for both substrates. The K,,, for L-alanine is 3.7 X 10m3 M and the K,,, for y,bdioxovalerate is 2.4 x 10e4 M. Plots of l/y,&dioxovalerate against l/v at varying alanine concentrations suggested a ping-pong reaction mechanism. Although the enzyme appeared to be a typical transaminase, exhaustive experiments failed to demonstrate reversibility of the reaction. The capacity of y,b-dioxovalerate transaminase to synthesize b-aminolevulinic acid appears to be far greater than the capacity of &aminolevulinic acid synthase from the same source. The possibility that y,& dioxovalerate transaminase plays a role in the biosynthesis of B-aminolevulinic acid in uiuo must be considered.