3-Fluoro-3-deoxycitrate

A probe for mechanistic study of citrate-utilizing enzymes

Steven E. Rokita, P. Srere, Christopher T. Walsh

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The interaction of a novel fluorinated analogue of citrate, 3-fluoro-3-deoxycitrate (3-fluorocitrate), with the four known citrate-processing enzymes is described in this report. Three of the citrate-processing enzymes, citrate synthase, ATP citrate lyase, and citrate lyase, catalyze reversible aldol-type condensations. The fate of 3-fluorocitrate with each enzyme is uniquely related to their mechanisms of action. For citrate synthase, 3-fluorocitrate is a competitive inhibitor. 3-Fluorocitrate is a substrate for the carboxylate activation half-reaction catalyzed by ATP citrate lyase and induces a net ATPase action during conversion to 3-fluorocitryl-S-coenzyme A. Because of the unusual mechanism of citrate cleavage catalyzed by bacterial citrate lyase, 3-fluorocitrate is a mechanism-based inhibitor, acting at two points during turnover of the acetyl enzyme. The fourth citrate-processing enzyme, aconitase, does turn over 3-fluorocitrate catalytically. This enzyme, catalyzing a dehydration and rehydration of citrate, also catalyzes the elimination of HF from 3-fluoro-citrate, yielding cis-aconitate and fluoride.

Original languageEnglish
Pages (from-to)3765-3774
Number of pages10
JournalBiochemistry
Volume21
Issue number16
Publication statusPublished - 1982

Fingerprint

Citric Acid
citrate (pro-3S)-lyase
Enzymes
ATP Citrate (pro-S)-Lyase
Citrate (si)-Synthase
Aconitic Acid
Processing
Aconitate Hydratase
Fluid Therapy
Coenzyme A
Dehydration
Fluorides
Adenosine Triphosphatases
Condensation
Chemical activation
Substrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

3-Fluoro-3-deoxycitrate : A probe for mechanistic study of citrate-utilizing enzymes. / Rokita, Steven E.; Srere, P.; Walsh, Christopher T.

In: Biochemistry, Vol. 21, No. 16, 1982, p. 3765-3774.

Research output: Contribution to journalArticle

Rokita, Steven E. ; Srere, P. ; Walsh, Christopher T. / 3-Fluoro-3-deoxycitrate : A probe for mechanistic study of citrate-utilizing enzymes. In: Biochemistry. 1982 ; Vol. 21, No. 16. pp. 3765-3774.
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