Reaffirmation That Metabolism of Polyamines by Bovine Plasma Amine Oxidase Occurs Strictly at the Primary Amino Termini

Younghee Lee,Lawrence M Sayre

doi:10.1074/jbc.273.31.19490

Abstract

Oxidation of the biologically important polyamines spermine and spermidine by plasma amine oxidase (PAO) was specified many years ago to occur at the terminal primary rather than internal secondary amine positions. However, the finding of sequential enzymatic conversion of spermine to spermidine and then to putrescine (1, 4-butanediamine) is superficially suggestive of metabolism at the secondary amine positions, and a recent publication (Houen, G., Bock, K., and Jensen, A. L. (1994) Acta Chem. Scand. 48, 52-60) claimed that the original interpretation of preferential "terminal" deamination does not stand up to scrutiny with modern methods of analysis. We herein demonstrate that the findings cited in support of secondary amine deamination can arise artifactually from spontaneous elimination/addition reactions following initial metabolism at the terminal positions of 3-(aminopropyl)amines. We further find no evidence for the ability of PAO to metabolize the secondary amine position in homospermidine, which is devoid of such complicating side reactions. Our results support the original claimed specificity of PAO for the primary amino termini of polyamines, all of which are consistent with the general finding that the quinone-dependent copper amine oxidases specifically metabolize primary amines.

Highlights

One piece of evidence obtained by the Tabor group in support of metabolism of polyamines at the terminal rather than internal amino groups was their quantitation of the released ammonia (1)
Reaction of Homospermidine with Bovine Plasma Amine Oxidase—As an alternative approach to resolving the question of primary versus secondary amine metabolism of polyamines by BPAO, we investigated homospermidine as a substrate to avert the complication of acrolein elimination following deamination
We have demonstrated that 3-aminopropanal, observed as key evidence of oxidation of polyamines at the secondary amino group by BPAO, could be generated under the conditions of oxidation at the primary amino group

Summary

Introduction

It was very surprising to us to see the provocative claim by Houen et al (10) that the metabolism of polyamines (spermine and spermidine) by plasma amine oxidases occurs principally at the secondary rather than primary amine centers. A review of the literature published since the initial studies by the Tabor group reveals that the formation of spermidine and putrescine had been consistently observed (11–13), Bachrach and co-workers (14) interpreted this to be a consequence not of secondary amine oxidation but of spontaneous elimination of acrolein by the labile aminopropionaldehyde products of terminal deamination (Scheme 2).

Results

Conclusion