Molecular Pharmacology, Vol 13, 378-381, Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics

Inactivation of a Flavin-Linked Oxidase, N,N-Dimethylglycine Oxidase, in Vivo and in Vitro

¹ Laboratoire de Chimie Hétéro-organique, U.E.R. Sciences, Université de Bretagne Occidentale, 29283 Brest Cedex, France

Attention is focused on mechanistic proposals concerning the unique inhibitory properties of N-allyl or N-propargyl substituents toward flavin-linked oxidases such as N,N-dimethylglycine oxidase. It is concluded that inhibitory substrates act through the formation of alkylating species, which can react directly with an enzyme site without the intermediacy of free aldehydes. These results extend and consolidate the concept of enzyme inactivation by inhibitory substrates or "suicide substrates." The activity displayed in vivo by the N,N-dimethylglycine oxidase inhibitory substrates demonstrates the practical potential of suicide substrates in molecular pharmacology and chermotherapy.

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ACKNOWLEDGMENTS We thank Dr. B. Belleau, McGill University, Montreal, for several helpful discussions, and Dr. G. Sturtz, Université de Bretagne Occidentale, for his generous help and provision of facilities.