Inactivation of γ-aminobutyric acid aminotransferase by l-3-chloroalanine hydroxamate

Richard B. Silverman*, Gregory T. Olson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


The mechanism of inactivation of γ-aminobutyric acid aminotransferase (GABA-AT) by l-3-chloroalanine hydroxamate (1) was investigated. Inactivation of [3H]PLP-reconstituted GABA-AT with 1 followed by denaturation gave no PMP or enamine adduct to the PLP; however, a new unknown metabolite was observed which was identical to the metabolite formed upon inactivation of GABA-AT by l-cycloserine. Time-dependent inactivation occurs, but the kinetics are second order; the rate of inactivation increases with time. After inactivation occurs the addition of fresh enzyme results in a faster rate of inactivation than prior to the initial inactivation. This indicates that the actual inactivator is generated from l-3-chloroalanine hydroxamate, and is not l-3-chloroalanine hydroxamate itself. Added gabaculine-inactivated enzyme to fresh enzyme does not increase the rate of inactivation, suggesting that the conversion of l-3-chloroalanine hydroxamate to the active form is not catalyzed by peripheral amino acid residues. l-3-Chloroalanine hydroxamate was shown to undergo buffer-catalyzed cyclization to l-cycloserine, which is the actual inactivator of GABA-AT.

Original languageEnglish (US)
Pages (from-to)11-18
Number of pages8
JournalBioorganic and Medicinal Chemistry
Issue number1
StatePublished - Jan 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


Dive into the research topics of 'Inactivation of γ-aminobutyric acid aminotransferase by l-3-chloroalanine hydroxamate'. Together they form a unique fingerprint.

Cite this