Molecular cloning and sequencing of a guinea pig cytochrome P4502D (CYP2D16): high level expression in adrenal microsomes.

Studies were done to characterize a guinea pig adrenal microsomal P450 that had been linked with xenobiotic metabolism in the inner zone of the gland. N-terminal amino acid sequencing of the isolated protein revealed homology with members of the CYP2D subfamily. A human CYPD2D6 cDNA probe was used to screen a guinea pig adrenal cDNA library and a full-length clone was obtained having an open reading frame encoding a 500 amino acid protein. The sequence was found to be highly homologous with all members of the CYP2D subfamily and was designated CYP2D16. The N-terminal sequence of 38 amino acids obtained from the protein microsequencing was identical to that deduced from the nucleotide sequence of the cloned CYP2D16. Northern blot analysis confirmed that CYP2D16 is expressed at high levels in the inner zone of the guinea pig adrenal cortex. The results suggest that CYP2D16 may account, at least in part, for the high rates of xenobiotic metabolism in the guinea pig adrenal.