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

• DOI: 10.1038/ncomms16018
• Publication Date: 2017-07-10T09:35:58Z
• Authors: Mohammad Tauqeer ...; Viridiana Olin-Sa...; Anna Stincone; Markus A. Keller; Aleksej Zelezniak; Ben F. Luisi; Markus Ralser
• Keywords: Compartmentalization (fire protection); Metabolic network; Metabolome; Metabolic pathway

Metabolites can inhibit the enzymes that generate them. To explore general nature of metabolic self-inhibition, we surveyed enzymological data accrued from a century experimentation and generated genome-scale enzyme-inhibition network. Enzyme inhibition is often driven by essential metabolites, affects majority biochemical processes, executed structured network whose topological organization reflecting chemical similarities exist between metabolites. Most inhibitory interactions are competitive, emerge in close neighbourhood inhibited enzymes, result structural substrate inhibitors. Structural constraints also explain one-third allosteric inhibitors, finding rationalized crystallographic analysis allosterically L-lactate dehydrogenase. Our findings suggest primary cause enzyme not evolution regulatory metabolite-enzyme interactions, but finite diversity prevalent within metabolome. In eukaryotes, compartmentalization minimizes inevitable alleviates self-inhibition places on metabolism.