人类酒精脱氢酶家族在乙醇代谢的功能评估:初步的新陈代谢的重要意义。
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李SL,洲GY,姚明CT,吴CW,阴SJ
人类酒精脱氢酶家族在乙醇代谢的功能评估:初步的新陈代谢的重要意义。
酒精实验研究杂志2006年7月,30 (7):1132 - 42。
- PubMed ID
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16792560 (在PubMed]
- 文摘
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背景:乙醇脱氢酶(ADH)乙醇代谢的主要酶的哺乳动物。人类抗利尿激素构成一个独特的复杂酶家族没有等效对应的实验啮齿动物。本研究进行定量评估人类ADH同功酶的相对贡献和异型酶肝和胃乙醇代谢的整个家庭。方法:对乙醇氧化动力学参数重组人类类我ADH1A ADH1B1, ADH1B2, ADH1B3, ADH1C1, ADH1C2;二类ADH2;第三类ADH3;和第四类ADH4决定在0.1磷酸钠在pH值7.5范围广泛的底物浓度在0.5毫米NAD +。复合器官稳态数值公式建立了乙醇间隙通过总结的动力学方程组成同功酶/异型酶在肝脏和胃粘膜评估内容与不同的基因型。结果:在ADH1B * 1个人,ADH1B1和ADH1C异型酶被发现的主要贡献者hepatic-alcohol间隙;ADH2只做出了巨大的贡献在高乙醇浓度(> 20毫米)。 ADH1B2 was the major hepatic contributor in ADH1B*2 individuals. ADH1C allozymes were the major contributor at low ethanol (< 2 mM), whereas ADH1B3 the major form at higher levels (> 10 mM) in ADH1B*3 individuals. For gastric mucosal-alcohol clearance, the relative contributions of ADH1C allozymes and ADH4 were converse as ethanol concentration increased. It was assessed that livers with ADH1B*1 may eliminate approximately 95% or more of single-passed ethanol as inflow sinusoidal alcohol reaches approximately 1 mM and that stomachs with different ADH1C genotypes may remove 20% to 30% of single-passed alcohol at the similar level in mucosal cells. CONCLUSIONS: This work provides just a model, but a strong one, for quantitative assessments of ethanol metabolism in the human liver and stomach. The results indicate that the hepatic-alcohol clearance of ADH1B*2 individuals is higher than that of the ADH1B*1 and those of the ADH1B*3 versus the ADH1B*1 vary depending on sinusoidal ethanol levels. The maximal capacity for potential alcohol first-pass metabolism in the liver is greater than in the stomach.