مرور کوتاهی بر سوبستراها و مهار کنندههای آمین اکسیداز حاوی مس

Title

Minireview of substrates and inhibitors of copper containing amine oxidases

English Abstract

Copper-containing amine oxidases (AOs) are widespread in nature, occurring in both prokaryotic and eukaryotic organisms. They catalyze the oxidative deamination of primary amines to aldehydes with a ping-pong mechanism consisting of a trans-amination, followed by the transfer of two electrons to molecular oxygen which is reduced to H2O2. In addition to copper, they contain an organic prosthetic group, tri-hydroxyphenylalanine quinone (TPQ).TPQ originate from tyrosine residue with post-translationally oxidiation. The main substrates for amine oxidases are 1.4-diaminobutane (putrescine) and 1.5-diaminopentane (cadaverine). Major advances have been made during the last decade toward understanding the structure/function relationships of the active site in Cu/TPQ amine oxidases using specific inhibitors. Reversible inhibitor binds theenzyme non-covalently and enzyme activity can be restored when the inhibitor removed. Competitive inhibitors of plant AOs were found to be diamino- or monoaminino-ketonic compounds and some alkaloids, Bivalent transition metals make complexes with diamines, and the monoamine cysteamine. Substances binding the enzyme at a different site from that for the substrate produce the non-competitive type of inhibition. The non-competitive inhibitor can bind either to the enzyme giving an inactive complex enzyme–inhibitor (EI), or to the ES complex giving inacative ternary complex ESI. The most effective irreversible inhibitors of plant AOs are carbonyl group reagents, like substituted hydrazines, interacting with TPQ cofactor.1.4-Diamino-2-pentyne and 1.4-Diamino-2-butyne are examples of mechanism-based inactivators for Cu-AOs.

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