Holmes R S, Albanese R, Whitehead F D, Duley J A
J Exp Zool. 1981 Aug;217(2):151-7. doi: 10.1002/jez.1402170202.
Electrophoretic variants for the stomach isozyme (ADH-C2) and liver isozyme (ADH-A2) of alcohol dehydrogenase in strains of Mus musculus have been used in genetic analyses to demonstrate close linkage between the structural genes (Ahd-3 and Adh-1, respectively) encoding these enzymes. No recombinants were observed between these loci among 126 backcross animals, which places them less than 0.8 centimorgans apart. Previous studies have positioned Adh-3, and a temporal locus (ADh-3t), on chromosome 3 (Holmes, "79; Holmes et al., "80). Kinetic analyses on partially purified preparations of these isozymes have demonstrated widely divergent catalytic properties and inhibitor specificities. The liver isozyme exhibited Michaelis constants that were nearly 3 orders of magnitude lower than the stomach isozyme for various alcohol and aldehyde substrates. Moreover, aminopropyl pyrazole strongly inhibited ADH-A2 (Ki=1.2M), whereas ADH-C2 was insensitive to inhibition under the conditions used. It is proposed that Adh-1 and Adh-3 are products of a recent gene duplication event during mammalian evolution and that considerable divergence in the active sites of these enzymes and the "temporal" genes controlling loci expression in differentiated tissues has subsequently occurred.
小家鼠品系中酒精脱氢酶的胃同工酶（ADH - C2）和肝同工酶（ADH - A2）的电泳变体已用于遗传分析，以证明编码这些酶的结构基因（分别为Ahd - 3和Adh - 1）之间存在紧密连锁。在126只回交动物中，未观察到这些基因座之间的重组体，这表明它们之间的距离小于0.8厘摩。先前的研究已将Adh - 3和一个时间基因座（ADh - 3t）定位在3号染色体上（霍姆斯，1979年；霍姆斯等人，1980年）。对这些同工酶部分纯化制剂的动力学分析表明，它们的催化特性和抑制剂特异性差异很大。对于各种酒精和醛底物，肝同工酶的米氏常数比胃同工酶低近3个数量级。此外，氨丙基吡唑强烈抑制ADH - A2（Ki = 1.2M），而在所用条件下ADH - C2对抑制不敏感。有人提出，Adh - 1和Adh - 3是哺乳动物进化过程中近期基因复制事件的产物，随后这些酶的活性位点以及控制分化组织中基因座表达的“时间”基因发生了相当大的分歧。
