Characterization of ethanol-inducible human liver N-nitrosodimethylamine demethylase.
Through the use of monospecific antibodies directed against hepatic cytochrome P-450j, an enzyme induced in rats treated with ethanol or isoniazid, we have purified from human liver the related cytochrome P-450 termed HLj. HLj resembles rat P-450j and P-450 LM3a, the homologous cytochrome in rabbit liver, in its NH2-terminal amino acid sequence, in being in highest concentration in liver microsome samples prepared from two patients intoxicated by ethanol and one patient given isoniazid, and in catalyzing the metabolic activation of the procarcinogen N-nitrosodimethylamine. Furthermore, each of nine human liver RNA samples contained a species of mRNA hybridizable to a cloned HLj cDNA. We conclude that HLj is related by structure, function, and some regulatory characteristics to rat P-450j and rabbit P-450 LM3a, cytochromes critical for metabolism of several clinically relevant cytotoxic and carcinogenic agents.
D000328:Adult; D000368:Aged; D000906:Antibodies; D000936:Antigen-Antibody Complex; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004247:DNA / Q000302:isolation & purification; D004790:Enzyme Induction; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis* / Q000235:genetics
D000906:Antibodies; D000936:Antigen-Antibody Complex; D000431:Ethanol; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating