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. 1987 Jan 1;241(1):305–307. doi: 10.1042/bj2410305

Decarboxylation of alpha-difluoromethylornithine by ornithine decarboxylase.

A E Pegg, K A McGovern, L Wiest
PMCID: PMC1147558  PMID: 3105526

Abstract

The mechanism of inactivation of rodent ornithine decarboxylase by alpha-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 enzymic decarboxylation of the inhibitor leads to the generation of a conjugated imine, which then alkylates a nucleophilic residue on the enzyme.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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