Reaction between sheep liver mitochondrial aldehyde dehydrogenase and various thiol-modifying reagents.
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.
Department of Chemistry and Biochemistry, Massey University, Palmerston North, New Zealand.
K M
KM
Loomes
T M
TM
Kitson
D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives / Q000494:pharmacology; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D004220:Disulfides; D004789:Enzyme Activation; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D011725:Pyridines / Q000494:pharmacology; D012756:Sheep; D013439:Sulfhydryl Reagents / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology
D004220:Disulfides; D011725:Pyridines; D013439:Sulfhydryl Reagents; D013777:Tetrazoles; C060766:1-methyl-5-(methyldithio)-1H-tetrazole; C001105:2,2'-dipyridyl disulfide; C007542:4,4'-dipyridyl disulfide; D015082:2,2'-Dipyridyl; C048500:5,5'-dithiobis(1-methyltetrazole); D000444:Aldehyde Dehydrogenase