Modification of thiol groups in cytoplasmic aldehyde dehydrogenase.
It is proposed that cytoplasmic aldehyde dehydrogenase possesses a pair of important reactive thiol groups, A and B. Group A is labelled by disulfiram and the enzyme is inactivated; subsequently group B displaces the dithiocarbamate label and an enzymic disulphide is formed. On the other hand, it appears that group B is labelled by 2,2'-dithiodipyridine resulting in activation of the enzyme. Again, the label (2-thiopyridone) is later displaced, this time presumably by group A, giving rise to loss of enzymic activity and formation of the same disulphide species as is produced by disulfiram. Methyl diethylthiocarbamyl disulphide and methyl 2-pyridyl disulphide supply the same label (MeS-) but the first compound inactivates the enzyme while the second activates it. It is concluded that the first of these reagents modifies group A and the second group B. It appears that methyl 4-pyridyl disulphide may react non-specifically with both groups A and B. Group A is a possible candidate for a catalytically essential nucleophile in the actions of aldehyde dehydrogenase.
D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives / Q000494:pharmacology; D000444:Aldehyde Dehydrogenase / Q000032:analysis*; D000818:Animals; D003593:Cytoplasm / Q000201:enzymology; D004220:Disulfides; D004221:Disulfiram / Q000494:pharmacology; D009243:NAD / Q000494:pharmacology; D012756:Sheep; D013438:Sulfhydryl Compounds / Q000032:analysis*
D004220:Disulfides; D013438:Sulfhydryl Compounds; D009243:NAD; C001105:2,2'-dipyridyl disulfide; D015082:2,2'-Dipyridyl; D000444:Aldehyde Dehydrogenase; D004221:Disulfiram