Decarboxylation of α-difluoromethylornithine by ornithine decarboxylase

A. E. Pegg, K. A. McGovern, L. Wiest

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

The mechanism of inactivation of rodent ornithine decarboxylase by α-difluoromethylornithine (DFMO) was studied using the inhibitor labelled with 14C in both the 1 and the 5 positions. [1-14C]DFMO was a substrate and was decarboxylated by the enzyme yielding 14CO2. A radioactive metabolite derived from [5-14C]DFMO was bound to the enzyme, and the extent of binding paralleled the irreversible inactivation of ornithine decarboxylase. The partition ratio of decarboxylation to binding was approx. 3.3. These results provide support for the postulated mechanism of action of DFMO [metcalf, Bey, Danzin, Jung, Casera & Vevert (1978) J. Am. Chem. Soc. 100, 2551-2553], in which enzynmic decarboxylatio of the inhibitor leads to the generation of a conjugated imine, which then alkylates a nucleophilic residue on the enzyme.

Original languageEnglish (US)
Pages (from-to)305-307
Number of pages3
JournalBiochemical Journal
Volume241
Issue number1
DOIs
StatePublished - Jan 1 1987

Fingerprint

Eflornithine
Decarboxylation
Ornithine Decarboxylase
Enzymes
Imines
Metabolites
Rodentia
Substrates

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Pegg, A. E. ; McGovern, K. A. ; Wiest, L. / Decarboxylation of α-difluoromethylornithine by ornithine decarboxylase. In: Biochemical Journal. 1987 ; Vol. 241, No. 1. pp. 305-307.
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Decarboxylation of α-difluoromethylornithine by ornithine decarboxylase. / Pegg, A. E.; McGovern, K. A.; Wiest, L.

In: Biochemical Journal, Vol. 241, No. 1, 01.01.1987, p. 305-307.

Research output: Contribution to journalArticle

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