Panoutsopoulos Georgios I, Kouretas Demetrios, Gounaris Elias G, Beedham Christine
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Bradford, Bradford, West Yorkshire BD7 1DP, UK.
Basic Clin Pharmacol Toxicol. 2004 Dec;95(6):273-9. doi: 10.1111/j.1742-7843.2004.t01-1-pto950505.x.
2-phenylethylamine is an endogenous constituent of the human brain and is implicated in cerebral transmission. This bioactive amine is also present in certain foodstuffs such as chocolate, cheese and wine and may cause undesirable side effects in susceptible individuals. Metabolism of 2-phenylethylamine to phenylacetaldehyde is catalysed by monoamine oxidase B but the oxidation to its acid is usually ascribed to aldehyde dehydrogenase and the contribution of aldehyde oxidase and xanthine oxidase, if any, is ignored. The objective of this study was to elucidate the role of the molybdenum hydroxylases, aldehyde oxidase and xanthine oxidase, in the metabolism of phenylacetaldehyde derived from its parent biogenic amine. Treatments of 2-phenylethylamine with monoamine oxidase were carried out for the production of phenylacetaldehyde, as well as treatments of synthetic or enzymatic-generated phenylacetaldehyde with aldehyde oxidase, xanthine oxidase and aldehyde dehydrogenase. The results indicated that phenylacetaldehyde is metabolised mainly to phenylacetic acid with lower concentrations of 2-phenylethanol by all three oxidising enzymes. Aldehyde dehydrogenase was the predominant enzyme involved in phenylacetaldehyde oxidation and thus it has a major role in 2-phenylethylamine metabolism with aldehyde oxidase playing a less prominent role. Xanthine oxidase does not contribute to the oxidation of phenylacetaldehyde due to low amounts being present in guinea pig. Thus aldehyde dehydrogenase is not the only enzyme oxidising xenobiotic and endobiotic aldehydes and the role of aldehyde oxidase in such reactions should not be ignored.
2-苯乙胺是人类大脑的内源性成分，与大脑神经传递有关。这种生物活性胺也存在于某些食物中，如巧克力、奶酪和葡萄酒，可能会在易感个体中引起不良副作用。单胺氧化酶B催化2-苯乙胺代谢为苯乙醛，但其氧化为酸的过程通常归因于醛脱氢酶，而醛氧化酶和黄嘌呤氧化酶（若有）的作用则被忽略。本研究的目的是阐明钼羟化酶、醛氧化酶和黄嘌呤氧化酶在其母体生物胺衍生的苯乙醛代谢中的作用。用单胺氧化酶处理2-苯乙胺以生成苯乙醛，同时用醛氧化酶、黄嘌呤氧化酶和醛脱氢酶处理合成的或酶促生成的苯乙醛。结果表明，所有三种氧化酶都将苯乙醛主要代谢为苯乙酸，生成较低浓度的2-苯乙醇。醛脱氢酶是参与苯乙醛氧化的主要酶，因此在2-苯乙胺代谢中起主要作用，醛氧化酶的作用则不太显著。由于豚鼠体内黄嘌呤氧化酶含量低，它对苯乙醛的氧化没有贡献。因此，醛脱氢酶不是氧化外源性和内源性醛的唯一酶，醛氧化酶在这类反应中的作用不应被忽视。
