Mechanism of Inactivation of γ-Aminobutyric Acid-α-Ketoglutaric Acid Aminotransferase by 4-Amino-5-halopentanoic Acids

Richard B. Silverman*, Mark A. Levy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

(S)-4-Amino-5-halopentanoic acids were previously shown to irreversibly inhibit pig brain γ-aminobutyric acid- α-ketoglutaric acid aminotransferase, and a mechanism for the inactivation was proposed (Silverman, R. B., & Levy, M. A. (1980) Biochem. Biophys. Res. Commun. 95, 250). Evidence is presented to show that these compounds are mechanism- based inactivators, and experiments are described to elucidate their mechanism of action. The enzyme must be in the pyridoxal phosphate form for inactivation to occur, the proton of the inactivators is removed in a rate-determining step, and one fluoride ion is released from 4-amino-5-fluoropentanoic acid per active site labeled. The change in the optical spectrum of the enzyme during inactivation suggests that the coenzyme is converted into the pyridoxamine phosphate form. Every turnover of inactivator leads to an inactivation event, i.e., the partition ratio is zero.

Original languageEnglish (US)
Pages (from-to)1197-1203
Number of pages7
JournalBiochemistry
Volume20
Issue number5
DOIs
StatePublished - Mar 1981

ASJC Scopus subject areas

  • Biochemistry

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