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The Effect of 5,5‘‐Dithiobis(l‐methyItetrazole) on Cytoplasmic Aldehyde Dehydrogenase and Its Implications for Cephalosporin‐Alcohol Reactions
Author(s) -
Kitson Trevor M.
Publication year - 1986
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1986.tb05608.x
Subject(s) - disulfiram , aldehyde dehydrogenase , aldehyde , chemistry , in vivo , side chain , biochemistry , in vitro , alcohol , stereochemistry , antibiotics , acetaldehyde , thiol , alcohol dehydrogenase , enzyme , cephalosporin , ethanol , organic chemistry , biology , catalysis , polymer , microbiology and biotechnology
Cephalosporin antibiotics with a 1‐methyttetrazofe‐5‐thio side chain have the ability to cause an unpleasant flushing reaction if they are taken some time before the drinking of alcohol. It is proposed that the explanation for this is that the side chain becomes liberated In vivo and oxidized to 5,5dithiobis(1‐methyttetrazole) or to a mixed disulfide analogue which then inactivates aldehyde dehydrogenase. Support for this proposal is given by the results below concerning the interaction in vitro between the disulfides and sheep Hver cytoplasmic aldehyde dehydrogenase. 5,5Dithiobis(1‐methy!tetrazo!e) has a rapid and pronounced macthratory effect, very similar in many ways (though not identical) to that of disulfiram, to which K has a structural similarity. (Disulfiram is widely used therapeutically to deter alcoholics from drinking.) 1‐Methyl‐5‐methytthiotetrazole (which is a simple model of the antibiotics) and the free 1‐methyfte‐trazole‐5‐thiol have no effect on the enzyme in vitro, > but methyl 5‐(1‐methyftetrazoiyl) disulfide is a potent inactivator, this also supports the proposed pathway.