Metabolite concentrations and concentration ratios in metabolic regulation

Daniel E. Atkinson, Peter J. Roach, Jean S. Schwedes

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Simple computational and graphic models were used to illustrate necessary design constraints in the evolution of two aspects of metabolic control: regulation at the catalytic site by ratios of metabolic coupling factors such as the ATP/ADP/AMP system and the pyridine nucleotides, and endproduct feedback inhibition. The observed constancy of the ratios of the nucleotide coupling agents, especially of the adenylates, indicates that control in vivo must be exerted primarily by ratios of the components of the pools, and must be insensitive to pool size. Such response of appropriate enzymes has been observed in vitro. The model illustrates by graphs the effects of variation in enzyme affinity fo the nucleotide coupling agents, and of variation in the ratios of these affinities. The graphs demonstrate the previously recognized, but not as formally demonstrated, need for high affinity (low Michaelis constants relative to physiological concentrations) and for higher affinity for the product nucleotide than for the reactant. Similar calculations for enzymes subject to negative feedback control demonstrated that, even if the effect of a modifier on the affinity of binding of substrate is very large, a sensitive response to modifier concentration cannot be attained if the reaction catalyzed is first order with respect to substrate and modifier. The cooperativity that is observed in such cases is thus a necessary design feature without which effective negative feedback could not have evolved.

Original languageEnglish (US)
Pages (from-to)391-411
Number of pages21
JournalAdvances in Enzyme Regulation
Volume13
Issue numberC
DOIs
StatePublished - 1975
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Cancer Research

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