Feedforward inhibition in biosynthetic pathways: inhibition of the aminoacyl-tRNA synthetase by the penultimate product

Abstract

Inhibition of the aminoacyl-tRNA synthetase by the penultimate product of a pathway for the biosynthesis of an amino acid has been reported for several pathways in many different types of organisms. A regulatory role for this mechanism often has been suggested, although there is some conflicting experimental evidence. The significance of such feedforward inhibition is examined here by mathematical analysis. The techniques that have proved successful in the analysis of control by feedback inhibition--showing that the nearly universal pattern of end-product inhibition is an optimal design--indicate that feedforward inhibition by the penultimate product does not contribute significantly to the functional effectiveness of regulation at the level of enzymatic activity. Feedforward inhibition by the penultimate product may have no physiological role, or it may be involved in differential signalling of intra- and extracellular changes and/or in directing the metabolic flow in branched pathways. These possibilities are discussed in light of analytical results presented in this paper and published experimental evidence.