Panoutsopoulos Georgios I
Department of Experimental Pharmacology, Medical School, Athens University, Athens, Greece.
Int J Toxicol. 2005 Mar-Apr;24(2):103-9. doi: 10.1080/10915810590936373.
Phenylacetaldehyde is formed when the xenobiotic and biogenic amine 2-phenylethylamine is inactivated by a monoamine oxidase-catalyzed oxidative deamination. Exogenous phenylacetaldehyde is found in certain foodstuffs such as honey, cheese, tomatoes, and wines. 2-Phenylethylamine can trigger migraine attacks in susceptible individuals and can become fairly toxic at high intakes from foods. It may also function as a potentiator that enhances the toxicity of histamine and tyramine. The present investigation examines the metabolism of phenylacetaldehyde to phenylacetic acid in freshly prepared and in cryopreserved guinea pig liver slices. In addition, it compares the relative contribution of aldehyde oxidase, xanthine oxidase, and aldehyde dehydrogenase in the oxidation of phenylacetaldehyde using specific inhibitors for each oxidizing enzyme. The inhibitors used were isovanillin for aldehyde oxidase, allopurinol for xanthine oxidase, and disulfiram for aldehyde dehydrogenase. In freshly prepared liver slices, phenylacetaldehyde was converted mainly to phenylacetic acid, with traces of 2-phenylethanol being present. Disulfiram inhibited phenylacetic acid formation by 80% to 85%, whereas isovanillin inhibited acid formation to a lesser extent (50% to 55%) and allopurinol had little or no effect. In cryopreserved liver slices, phenylacetic acid was also the main metabolite, whereas the 2-phenylethanol production was more pronounced than that in freshly prepared liver slices. Isovanillin inhibited phenylacetic acid formation by 85%, whereas disulfiram inhibited acid formation to a lesser extent (55% to 60%) and allopurinol had no effect. The results in this study have shown that, in freshly prepared and cryopreserved liver slices, phenylacetaldehyde is converted to phenylacetic acid by both aldehyde dehydrogenase and aldehyde oxidase, with no contribution from xanthine oxidase. Therefore, aldehyde dehydrogenase is not the only enzyme responsible in the metabolism of phenylacetaldehyde, but aldehyde oxidase may also be important and thus its role should not be ignored.
当外源性生物胺2-苯乙胺被单胺氧化酶催化的氧化脱氨作用失活时，会形成苯乙醛。在某些食品如蜂蜜、奶酪、番茄和葡萄酒中可发现外源性苯乙醛。2-苯乙胺可引发易感个体的偏头痛发作，且在从食物中高摄入量时可能具有相当的毒性。它还可能作为一种增效剂，增强组胺和酪胺的毒性。本研究考察了苯乙醛在新鲜制备的和冷冻保存的豚鼠肝切片中代谢为苯乙酸的过程。此外，使用每种氧化酶的特异性抑制剂，比较了醛氧化酶、黄嘌呤氧化酶和醛脱氢酶在苯乙醛氧化中的相对贡献。所使用的抑制剂分别为异香草醛（用于醛氧化酶）、别嘌呤醇（用于黄嘌呤氧化酶）和双硫仑（用于醛脱氢酶）。在新鲜制备的肝切片中，苯乙醛主要转化为苯乙酸，同时存在微量的2-苯乙醇。双硫仑抑制苯乙酸形成80%至85%，而异香草醛对酸形成的抑制作用较小（50%至55%），别嘌呤醇几乎没有作用。在冷冻保存的肝切片中，苯乙酸也是主要代谢产物，而2-苯乙醇的生成比新鲜制备的肝切片中更明显。异香草醛抑制苯乙酸形成85%，而双硫仑对酸形成的抑制作用较小（55%至60%），别嘌呤醇没有作用。本研究结果表明，在新鲜制备的和冷冻保存的肝切片中，苯乙醛通过醛脱氢酶和醛氧化酶均转化为苯乙酸，黄嘌呤氧化酶无作用。因此，醛脱氢酶不是苯乙醛代谢的唯一负责酶，但醛氧化酶也可能很重要，其作用不应被忽视。
