Middleton R J, Kacser H
Genetics. 1983 Nov;105(3):633-50. doi: 10.1093/genetics/105.3.633.
Although there are many in vitro studies of enzyme activity of genetic variants at the Adh locus in D. melanogaster, little is known about the corresponding metabolic activity in living flies. We report here such measurements of the metabolic flux in the conversion of ethanol to the two products, CO2 and lipids, for six different active genotypes, containing the predominant naturally recurring alleles and covering a threefold range of in vitro activity. In adult flies we have found nonsignificant differences between genotypes in metabolic flux when estimates for individual genotypes had standard errors of approximately 10% of the mean value. In vitro activities are, therefore, poor predictors of the physiological consequences of enzyme variation since such determinations ignore the interactions inherent in multienzyme systems. We have no evidence that heterozygote show overdominance either at the enzyme or the flux level. Since fitness differences between genotypes must be generated by physiological differences, investigations of polymorphisms should be based on in vivo studies.
虽然有许多关于黑腹果蝇Adh基因座遗传变异体酶活性的体外研究，但对于活蝇体内相应的代谢活性却知之甚少。我们在此报告了六种不同活性基因型将乙醇转化为两种产物（二氧化碳和脂质）的代谢通量测量结果，这些基因型包含主要的自然复发等位基因，且体外活性范围达三倍。在成年果蝇中，当个体基因型的估计值标准误差约为平均值的10%时，我们发现基因型之间的代谢通量差异不显著。因此，体外活性并不能很好地预测酶变异的生理后果，因为此类测定忽略了多酶系统中固有的相互作用。我们没有证据表明杂合子在酶水平或通量水平表现出超显性。由于基因型之间的适应性差异必定由生理差异产生，因此对多态性的研究应基于体内研究。
