Inhibition of aldehyde dehydrogenases in rat brain and liver by disulfiram and coprine.
Rats were treated with either coprine or disulfiram and the inhibition of aldehyde dehydrogenase (ALDH) in liver and brain mitochondria was measured with acetaldehyde, 3,4-dihydroxyphenylacetaldehyde (DOPAL), and succinate semialdehyde at different concentrations. The inhibition pattern was similar for both inhibitors, but the degree of inhibition was lower with disulfiram. The ALDH activity both in the liver and the brain was inhibited at low concentrations of acetaldehyde and DOPAL, but not with succinate semialdehyde. The high-Km enzyme activities with acetaldehyde were not inhibited in liver and brain. The activity at high concentration of DOPAL was inhibited in the liver, but only slightly affected in the brain, suggesting the presence of a brain enzyme with an intermediate Km value for DOPAL. In contrast with the results observed in vivo, it was found that the high-Km activities with acetaldehyde and DOPAL in brain mitochondrial preparations were more sensitive to the inhibitors in vitro than the low-Km activities. Kinetic studies on ALDH preparations from brain and liver mitochondria suggested that acetaldehyde and DOPAL are metabolized by the same low-Km ALDH.
D000445:Aldehyde Oxidoreductases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D000818:Animals; D001921:Brain / Q000201:enzymology*; D004221:Disulfiram / Q000494:pharmacology*; D005260:Female; D005973:Glutamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
D005973:Glutamine; C014423:coprine; D000445:Aldehyde Oxidoreductases; D004221:Disulfiram