Controls of citrate synthase activity

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The inhibition of citrate synthase by a variety of nucleotides and polycarboxylate compounds is not unexpected since many of the compounds are substrate analogs of citrate synthase. These effectors are interesting by virtue of the fact that many of them are intermediates and/or end products in the metabolic path of which citrate synthase can be considered the first committed step. As a consequence, it is possible to propose regulation of citrate synthase by ATP (or phosphorylation potential) by acyl CoA (acylation level) and NADH (redox potential). Aside from these putative controls, it is possible that the major control of citrate synthase activity is by changes in the concentration of its substrates acetyl CoA and oxalacetate. I discuss in this review the many factors that must be considered before one can decide whether or not interactions between metabolites and enzymes observed in an in vitro catalytic situation have metabolic relevance. These factors include 1) the concentrations of substrates at the enzyme site, 2) the concentrations of effectors at the enzyme site, 3) the presence of modifying substances, and 4) the difference in behavior of an enzyme at its concentration in vivo compared to its concentration in vitro. In the case of citrate synthase as is generally true for other enzymes, no accurate knowledge of these factors are available in vitro so that little can be said concerning the in situ control of citrate synthase, which may be the result of all the factors acting in concert. The studies of effectors on enzymes in vitro can only serve as a guideline for parameters to study when techniques are available to study control of enzymes in situ.

Original languageEnglish
Pages (from-to)1695-1710
Number of pages16
JournalLife Sciences
Volume15
Issue number10
DOIs
Publication statusPublished - Nov 15 1974

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this