Rietveld E C, de Zwart M, Cox P G, Seutter-Berlage F
Biochim Biophys Acta. 1987 Aug 5;914(2):162-9. doi: 10.1016/0167-4838(87)90059-8.
The influence of the steric hindrance of halogen substituents was investigated in vitro by measuring the activity of yeast aldehyde dehydrogenase (aldehyde: NAD(P)+ oxidoreductase, EC 1.2.1.5) and of aldehyde dehydrogenases in subcellular rat liver fractions with a series of ortho- and para-halo-substituted benzaldehydes as substrates. Upon an increase in the size of the halogen substituent (F, Cl, Br), the reactivity of yeast aldehyde dehydrogenase to ortho-substituted benzaldehydes decreased drastically. The same phenomenon was observed with the unspecific aldehyde dehydrogenases in three rat liver fractions; cytoplasm, mitochondria and microsomes. The corresponding para-halobenzaldehydes (F, Cl, Br, I) did not reveal large differences in reactivity to the various rat liver aldehyde dehydrogenases. The aldehyde dehydrogenases in the rat liver microsomal fraction exhibited most clearly the regiospecificity. Enzymatic oxidation of 4-bromobenzaldehyde was more than 30-times faster then the ortho-isomer. The findings in this investigation confirm the suggestion that the steric hindrance of bulky ortho-substituents of benzaldehydes account for the slowing down of the aldehyde dehydrogenase-catalyzed oxidation of benzaldehydes to corresponding benzoic acids. The enzymatic oxidation of microsomal aldehyde dehydrogenase is strongly influenced by steric effects of benzaldehydes, bearing a halogen in ortho-position. We think that the microsomal aldehyde dehydrogenase might be the principal enzyme responsible for oxidation of halobenzaldehydes in rat liver.
通过以一系列邻位和对位卤代苯甲醛为底物，测定酵母醛脱氢酶（醛：NAD(P)+氧化还原酶，EC 1.2.1.5）以及大鼠肝脏亚细胞组分中的醛脱氢酶活性，在体外研究了卤素取代基的空间位阻影响。随着卤素取代基（F、Cl、Br）尺寸的增加，酵母醛脱氢酶对邻位取代苯甲醛的反应性急剧下降。在大鼠肝脏的三个组分（细胞质、线粒体和微粒体）中的非特异性醛脱氢酶上也观察到了同样的现象。相应的对位卤代苯甲醛（F、Cl、Br、I）对各种大鼠肝脏醛脱氢酶的反应性没有显示出很大差异。大鼠肝脏微粒体组分中的醛脱氢酶最明显地表现出区域特异性。4-溴苯甲醛的酶促氧化速度比邻位异构体快30多倍。本研究中的发现证实了以下观点，即苯甲醛的邻位大取代基的空间位阻导致醛脱氢酶催化的苯甲醛氧化为相应苯甲酸的反应减慢。微粒体醛脱氢酶的酶促氧化受到邻位带有卤素的苯甲醛的空间效应的强烈影响。我们认为微粒体醛脱氢酶可能是大鼠肝脏中负责卤代苯甲醛氧化的主要酶。
