Polyamine oxidase, properties and functions

Abstract

Polyamine oxidase (PAO) is a FAD-dependent enzyme with a molecular mass of about 62 kDa, present with high activity in most tissues of vertebrates. Structural requirements of a substrate for PAO are two positively charged amino groups, separated by a short carbon chain and an alkyl substituent on one or both nitrogen atoms. Spermine and the monoacetyl derivatives N1-acetylspermine and N1-acetylspermidine appear to be the natural substrates. Spermidine is only poorly oxidized by PAO. Using O2, the substrates are oxidatively cleaved by PAO to form equimolar amounts of an amine, an aldehyde and hydrogen peroxide. PAO is an integral part of the polyamine interconversion cycle, a major intracellular regulatory system, which contributes to the maintenance of polyamine homeostasis in non-proliferating cells, including brain cells. Selective inactivators were used as tools in the elucidation of the functions of PAO. Interestingly, even long-term inactivation of PAO did not provoke behavioral changes in experimental animals, despite considerable changes in polyamine metabolism. PAO inactivation, however, improves the growth-inhibitory effects of inhibitors of polyamine biosynthetic enzymes and the antitumoral effects of some structural analogs of the polyamines.