ETHANOL EFFECTS ON MEMBRANE-BOUND ENZYMES

据推测，某些酶的活性可能是 有酗酒遗传倾向的标记。我们之前展示了 低氟刺激的血小板腺苷环化酶(AC)活性，以及 血小板单胺氧化酶(MAO)对体外培养的敏感性增加 乙醇抑制，有效区分酒精和 不酗酒的人。我们现在已经检查了遗传性 饮酒家庭中血小板氟化物刺激AC活性的研究 成员，并发现了具有主基因效应的家族遗传， 这种酶的活性。主要基因以孟德尔共基因的形式传递。 占主导地位。基础AC活动的传递更为复杂。调查结果 与氟刺激的AC活动的可能性相一致， 它在酗酒者家庭中作为单一的主基因传播， 可能代表着酗酒倾向的特征标记。交流电 还检测了同卵双胞胎和异卵双胞胎的血小板活性。 而同卵双胞胎的一致性更高，支持 这一指标的遗传力。血小板氟化物刺激的AC活性是 目前正在与其他几个可能的遗传标记进行比较 容易酗酒。先前的WESTERN和缝隙印迹分析 结果表明，血小板膜G(S-α)总量未见明显变化。 与氟刺激的AC活性显著相关。最新数据 提示刺激后的AC与刺激后的AC呈显著正相关 活性和霍乱毒素诱导的ADP核糖化。这些结果表明 这是G的质的差异，而不是量的差异(S-阿尔法) 可能是酗酒者血小板AC活性降低的原因之一。这些研究 描述将有助于确定观察到的差异是否 酒精者与非酒精者的血小板酶活性 基于基因，并可能是酗酒倾向的标志， 或者是乙醇消费的结果。

It has been postulated that the activities of certain enzymes may be markers of a genetic predisposition to alcoholism. We previously showed that low fluoride-stimulated platelet adenylate cyclase (AC) activity, and an increased sensitivity of platelet monoamine oxidase (MAO) to in vitro inhibition by ethanol, effectively discriminated alcoholic and non-alcoholic individuals. We have now examined the heritability of platelet fluoride-stimulated AC activity in families with alcoholic members, and have found familial transmission, with a major gene effect, for this enzyme activity. The major gene was transmitted as a Mendelian co- dominant. Transmission of basal AC activity was more complex. The findings are compatible with the possibility that fluoride-stimulated AC activity, which is transmitted as a single major gene in families of alcoholics, could represent a trait marker for a predisposition to alcoholism. AC activity was also assayed in platelets of monozygotic and dizygotic twins and concordance was higher in monozygotic twins, supporting the heritability of this measure. Platelet fluoride-stimulated AC activity is currently being compared with several other possible genetic markers of predisposition to alcoholism. Previous Western and slot blot analysis showed that the total quantity of G(S-alpha) in platelet membranes was not significantly correlated with fluoride-stimulated AC activity. Recent data indicates that there is a significant positive correlation of stimulated AC activity and cholera toxin-induced ADP-ribosylation. These results suggest that a qualitative, rather than a quantitative, difference in G(S-alpha) may contribute to lower platelet AC activity in alcoholics. The studies described will help to determine whether the observed differences in platelet enzyme activities between alcoholics and non-alcoholics are genetically based, and may be a marker for a predisposition to alcoholism, or are a consequence of ethanol consumption.