Loomes K M, Kitson T M
Department of Chemistry and Biochemistry, Massey University, Palmerston North, New Zealand.
Biochem J. 1989 Jul 1;261(1):281-4. doi: 10.1042/bj2610281.
Sheep liver mitochondrial aldehyde dehydrogenase reacts with 2,2'-dithiodipyridine and 4,4'-dithiodipyridine in a two-step process: an initial rapid labelling reaction is followed by slow displacement of the thiopyridone moiety. With the 4,4'-isomer the first step results in an activated form of the enzyme, which then loses activity simultaneously with loss of the label (as has been shown to occur with the cytoplasmic enzyme). With 2,2'-dithiodipyridine, however, neither of the two steps of the reaction has any effect on the enzymic activity, showing that the mitochondrial enzyme possesses two cysteine residues that must be more accessible or reactive (to this reagent at least) than the postulated catalytically essential residue. The symmetrical reagent 5,5'-dithiobis-(1-methyltetrazole) activates mitochondrial aldehyde dehydrogenase approximately 4-fold, whereas the smaller related compound methyl l-methyltetrazol-5-yl disulphide is a potent inactivator. These results support the involvement of mixed methyl disulphides in causing unpleasant physiological responses to ethanol after the ingestion of certain antibiotics.
绵羊肝脏线粒体醛脱氢酶与2,2'-二硫代二吡啶和4,4'-二硫代二吡啶的反应分两步进行：首先是快速的标记反应，随后是硫代吡啶酮部分的缓慢置换。对于4,4'-异构体，第一步产生酶的活化形式，然后在失去标记的同时失去活性（正如已证明在细胞质酶中发生的那样）。然而，对于2,2'-二硫代二吡啶，反应的两个步骤对酶活性均无任何影响，这表明线粒体酶具有两个半胱氨酸残基，与假定的催化必需残基相比，这两个残基必定更容易接近或更具反应性（至少对该试剂而言）。对称试剂5,5'-二硫代双-(1-甲基四唑)可使线粒体醛脱氢酶活化约4倍，而较小的相关化合物甲基1-甲基四唑-5-基二硫化物是一种有效的失活剂。这些结果支持了混合甲基二硫化物在摄入某些抗生素后对乙醇产生不良生理反应中所起的作用。
