Inhibition of Human Mitochondrial Aldehyde Dehydrogenase by Metabolites of Disulfiram and Structural Characterization of the Enzyme Adduct by HPLC-Tandem Mass Spectrometry
Ingest of disulfiram blocks the metabolism of acetaldehyde, the product of ethanol metabolism, by inhibiting hepatic mitochondrial aldehyde dehydrogenase (ALDH2), a key ene by virtue of its low Km for acetaldehyde (Mascher & Kikuta, 1992; Greenfield & Pietruszko, 1977). Disulfiram is rapidly reduced in vivo to N,N-diethyldithiocarbamate (DDC) (Cobby et al., 1977) which is further metabolized as shown in Scheme 1. The general consensus is that disulfiram is too short-lived in vivo to account for the inhibition of ALDH2 that one its metabolites is the ultimate inhibitor (Yourick & Faiman, 1991; Hart & man, 1992).
KeywordsGlutathione Adduct Ketone NADH Sulfoxide
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