Oxidative and Non-Oxidative Metabolomics of Ethanol
Oxidative and Non-Oxidative Metabolomics of Ethanol
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DOI：
10.2174/1389200217666160125113806
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发表时间：
2016-01-01
影响因子：
2.3
通讯作者：
Dinis-Oliveira, Ricardo J.
中科院分区：
文献类型：
--
作者：
Dinis-Oliveira, Ricardo J.
背景：众所周知，乙醇可导致显着的发病率和死亡率，许多相关的毒性作用可以通过其代谢特征来解释。目的：这项工作对乙醇的代谢进行了全面的回顾，重点关注主要和次要代谢物。方法：使用乙醇和相关已知代谢酶和代谢物的文本和结构查询进行详尽的文献检索。结果：代谢的主要途径是由胞质乙醇脱氢酶催化，其表现出多种同工酶和具有临床和法医学意义的遗传多态性。另外两种氧化途径，高度诱导型 CYP2E1 系统和过氧化物酶体过氧化氢酶可能在特定情况下具有相关性。除了氧化代谢外，乙醇还产生少量代谢物，例如乙基葡萄糖醛酸、硫酸乙酯、磷酸乙酯、亚硝酸乙酯、磷脂酰乙醇和脂肪酸乙酯。这些代谢物代表了替代生物标志物，因为它们可以在乙醇暴露后数小时或数天被检测到。结论：预计了解乙醇的代谢组学可能会提供更多见解，以更好地了解毒理学效应和剂量反应的变异性。
Background: It is well known that ethanol can cause significant morbidity and mortality, and much of the related toxic effects can be explained by its metabolic profile.Objective: This work performs a complete review of the metabolism of ethanol focusing on both major and minor metabolites.Method: An exhaustive literature search was carried out using textual and structural queries for ethanol and related known metabolizing enzymes and metabolites.Results: The main pathway of metabolism is catalyzed by cytosolic alcohol dehydrogenase, which exhibits multiple isoenzymes and genetic polymorphisms with clinical and forensic implications. Another two oxidative routes, the highly inducible CYP2E1 system and peroxisomal catalase may acquire relevance under specific circumstances. In addition to oxidative metabolism, ethanol also originates minor metabolites such as ethyl glucuronide, ethyl sulfate, ethyl phosphate, ethyl nitrite, phosphatidylethanol and fatty acid ethyl esters. These metabolites represent alternative biomarkers since they can be detected several hours or days after ethanol exposure.Conclusion: It is expected that knowing the metabolomics of ethanol may provide additional insights to better understand the toxicological effects and the variability of dose response.