The self-inhibitory nature of metabolic networks and its alleviation through compartmentalization.

ABSTRACT: Metabolites can inhibit the enzymes that generate them. To explore the general nature of metabolic self-inhibition, we surveyed enzymological data accrued from a century of experimentation and generated a genome-scale enzyme-inhibition network. Enzyme inhibition is often driven by essential metabolites, affects the majority of biochemical processes, and is executed by a structured network whose topological organization is reflecting chemical similarities that exist between metabolites. Most inhibitory interactions are competitive, emerge in the close neighbourhood of the inhibited enzymes, and result from structural similarities between substrate and inhibitors. Structural constraints also explain one-third of allosteric inhibitors, a finding rationalized by crystallographic analysis of al

SUBMITTER: Alam MT 

PROVIDER: S-EPMC5508129 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature