Alcohol dehydrogenase and catalase content in perinatal infant and adult livers: Potential influence on neonatal alcohol metabolism
Alcohol dehydrogenase and catalase content in perinatal infant and adult livers: Potential influence on neonatal alcohol metabolism
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DOI：
10.1016/j.toxlet.2007.01.012
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发表时间：
2007-03-30
影响因子：
3.5
通讯作者：
Hill, Dennis W.
中科院分区：
文献类型：
--
作者：
Tran, Minh-Nguyet;Wu, Alan H. B.;Hill, Dennis W.
甲醇和乙醇主要通过成人的乙醇脱氢酶（ADH）系统代谢。在饱和底物浓度下，血液酒精浓度以恒定速率下降（即，零级动力学）。次要代谢醇途径包括通过细胞色素P450系统和过氧化氢酶的氧化。我们先前报告了一个5周大的婴儿在异常的甲醇浓度（1148 mg/dL）中毒后存活。由于消除速率遵循一级动力学，我们提出，一个替代的非饱和醇代谢酶系统，如过氧化氢酶是负责这一观察。在这项研究中，我们开发和优化的酶免疫分析组织ADH和过氧化氢酶，并测量这些酶的浓度在肝脏的18名成人和7名围产期婴儿尸检。围产期婴儿的平均ADH含量比成人低约10倍（分别为0.11 +/- 0.09 g/kg和1.00 +/- 0.37 g/kg肝湿重）。ADH的α-α同工酶是围产期婴儿的主要同工酶，而在成人肝脏中发现了几种同工酶。对于过氧化氢酶，一半的围产期婴儿（n = 4）与成人的含量大致相同（0.32 +/- 0.03 g/kg与0.37 +/- 0.20 g/kg湿重，p = NS），而其他三名围产期婴儿的浓度显著较高（1.55 +/- 0.48 g/kg对0.37 +/- 0.02 g/kg湿重，p < 0.05）。在围产期婴儿，这些结果表明，过氧化氢酶可能发挥更突出的作用，在酒精的代谢比ADH系统，并可能解释一级动力学的高甲醇和乙醇中毒的情况下报告的结果。(C)2007年由Elsevier爱尔兰有限公司出版。
Methanol and ethanol are primarily metabolized through the alcohol dehydrogenase (ADH) system in adults. Under saturating substrate concentrations, blood alcohol concentrations decline at a constant rate (i.e., zero-order kinetics). Minor metabolic alcohol pathways include oxidation through the cytochrome P450 system and catalase. We previously reported a 5-week-old infant that survived intoxication at an exceptional methanol concentration (1148 mg/dL). As the rate of elimination followed first-order kinetics, we proposed that an alternate non-saturating alcohol metabolizing enzyme system such as catalase was responsible for this observation. In this study, we developed and optimized enzyme immunoassays for tissue ADH and catalase, and measured the concentration of these enzymes in the livers of 18 adults and 7 perinatal infants obtained from autopsies. The mean ADH content of perinatal infants was approximately 10-fold lower than adults (0.11 +/- 0.09 g/kg versus 1.00 +/- 0.37 g/kg liver wet weight, respectively). The alpha alpha isoenzyme of ADH was the predominant isoform in perinatal infants, while there were several isoenzymes found in adult livers. For catalase, half of the perinatal infants (n = 4) had roughly equal amounts as adults (0.32 +/- 0.03 g/kg versus 0.37 +/- 0.20 g/kg wet weight, p = NS), while three other perinatal infants had significantly higher concentrations (1.55 +/- 0.48 g/kg versus 0.37 +/- 0.02 g/kg wet weight, p < 0.05). In the perinatal infants, these results suggest that catalase may play a more prominent role in the metabolism of alcohols than does the ADH system and may explain the finding of first-order kinetics in case reports of high methanol and ethanol intoxication. (C) 2007 Published by Elsevier Ireland Ltd.