title: Debrisoquine metabolism and CYP2D expression in marmoset liver microsomes.
abstract: The objective of this study was to define CYP2D enzymes in marmoset (Callithrix jacchus) liver microsomes, both at the activity level using debrisoquine as the model substrate and at the protein level using antibodies raised to human CYP2D6. Marmoset liver microsomes were incubated with [(14)C]debrisoquine, and the structure of the generated metabolites was determined using liquid chromatography-tandem mass spectrometry and NMR. Marmoset liver microsomes were very effective in hydroxylating debrisoquine at various positions. Although 4-hydroxydebrisoquine was formed, in contrast to rat and human it was only a minor metabolite. Debrisoquine was more extensively hydroxylated in the 7, 5, 6, and 8 positions. In addition to the monohydroxylated metabolites, a dihydroxy metabolite, namely 6,7-dihydroxydebrisoquine, was identified. Finally, metabolites that had undergone ring opening were also detected but were not investigated further. Antibodies to CYP2D6 immunoreacted with protein in marmoset and human but not rat hepatic microsomes. In conclusion, we demonstrate that marmoset liver microsomes are effective in hydroxylating debrisoquine at various positions and that they contain a protein that is immunorelated to human CYP2D6.
authors: Department of In Vitro Metabolism, Huntingdon Life Sciences Ltd., Woolley Road, Alconbury, Huntingdon, Cambridgeshire, PE28 4HS, UK.
authors: Brian R
authors: BR
authors: Cooke
authors: S W Annie
authors: SW
authors: Bligh
authors: Z Richard
authors: ZR
authors: Cybulski
authors: Costas
authors: C
authors: Ioannides
authors: Michael
authors: M
authors: Hall
mesh_terms: D000818:Animals; D002144:Callithrix; D019389:Cytochrome P-450 CYP2D6 / Q000096:biosynthesis*; D003647:Debrisoquin / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D051381:Rats
chemical_list: D019389:Cytochrome P-450 CYP2D6; D003647:Debrisoquin