CONTROL OF ENZYME ACTIVITY BY CONCERTED FEEDBACK INHIBITION

Abstract

The phenomenon of concerted feedback inhibition of enzyme activity is described. This type of feedback control depends on the simultaneous action of two end products of a branched biosynthe-tic pathway. The enzyme studied, viz., [beta]-aspartokinase from the photo-synthetic bacterium Rhodopseudomonas capsulatus, is virtually insensitive to individual end products. The specific combination of L-lysine + L-threonine, however, causes effective inhibition. Concerted inhibition due to these amino acids is nontotal, reversible, and noncompetitive with respect to one of the substrates of the enzymatic reaction, namely, L-aspartate. Evidence is presented for the conclusion that the [beta]-aspartokinase possesses separate "regulatory sites" for L-lysine and L-threonine, which are distinct from the substrate (L-aspartate) sites. The probable role of concerted feedback inhibition in regulation of synthesis of aspartic family amino acids (lysine, threonine, isoleucine, methio-nine) in Rps capsulatus, and in branched pathways in general, is discussed.