UChA和UChB鼠线:代谢和遗传差异影响乙醇摄入。
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Quintanilla我,以色列Y, Sapag Tampier L
UChA和UChB鼠线:代谢和遗传差异影响乙醇摄入。
成瘾医学杂志2006年9月,11(3 - 4):310 - 23所示。
- PubMed ID
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16961761 (在PubMed]
- 文摘
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乙醇non-drinker (UChA)和铁(UChB)大鼠行来源于一个原始纯种殖民地已经选育出智利大学超过70代。这些线两个主要差异是显而易见的。(1)饮酒者老鼠显示明显比non-drinker老鼠更快急性宽容。在F2 UChA x UChB老鼠(所有基因的“重组”),急性高公差的后代喝预测高于低急性宽容。它进一步表明,high-drinker动物“学习”喝,从消费水平一半的最大消耗达到无限制的访问1个月后10%的乙醇和水。很可能获得宽容的基础是提高乙醇消费。(2)Non-drinker文献未见报道的等位基因的老鼠携带醛dehydrogenase-2 (Aldh2)编码酶的低亲和力Nicotinamide-adenine-dinuclectide (NAD +) Aldh2((2)),而酒鬼老鼠现在两个Aldh2等位基因(Aldh2 Aldh2(1)和(3))与NAD +四到五倍的高亲和力。此外,ALDH2由ALDH2编码(1)也显示了一个高33% Vmax比ALDH2编码的ALDH2(2)和(3)。最大的自愿乙醇摄入以下:Aldh2 UChA Aldh2(2) /(2) = 0.3 - -0.6克/公斤/天;Aldh2 UChB Aldh2(3) /(3) = 4.5 - -5.0克/公斤/天; UChB Aldh2(1)/Aldh2(1) = 7.0-7.5 g/kg/day. In F2 offspring of UChA x UChB, the Aldh2(2)/Aldh2(2) genotype predicts a 40-60% of the alcohol consumption. Studies also show that the low alcohol consumption phenotype of Aldh2(2)/Aldh2(2) animals depends on the existence of a maternally derived low-activity mitochondrial reduced form of nicotinamide-adenine-dinucleotide (NADH)-ubiquinone complex I. The latter does not influence ethanol consumption of animals exhibiting an ALDH2 with a higher affinity for NAD+. An illuminating finding is the existence of an 'acetaldehyde burst' in animals with a low capacity to oxidize acetaldehyde, being fivefold higher in UChA than in UChB animals. We propose that such a burst results from a great generation of acetaldehyde by alcohol dehydrogenase in pre-steady-state conditions that is not met by the high rate of acetaldehyde oxidation in mitochondria. The acetaldehyde burst is seen despite the lack of differences between UChA and UChB rats in acetaldehyde levels or rates of alcohol metabolism in steady state. Inferences are drawn as to how these studies might explain the protection against alcoholism seen in humans that carry the high-activity alcohol dehydrogenase but metabolize ethanol at about normal rates.