抄録
To date, it is very difficult to extrapolate the data obtained from experimental animals (for example rodents) to humans, since there are species differences in the characteristics of drug metabolising enzymes. The monkeys is often used for the preclinical study. However, the similarities for properties and capacities of drug metabolizing enzymes between monkeys and humans were not well recognized. Therefore, we started to characterize the drug metabolizing enzymes, especially cytochrome P450s, in non-human primates.
Four forms of cytochrome P450 enzymes (termed P450 CMLa-d) were purified from hepatic microsomes of cynomolgus monkeys. P450 CMLa was classified into the CYP2B subfamily, in its N-terminal amino acid sequence, catalytic activities, and immunochemical properties and act as a testosterone 16, 8-hydroxylase in cynomolgus monkseys. P450 CMLa is expressed constitutively as a minor form of P450 and is one of the forms inducible by phenobarbital. The nucleotide sequence of a cDNA coding for the monkey CYP2B was also determined and is now called CYP2B17. P450 CMLb and P450 CMLc purified from hepatic microsomes of cynomolgus monkeys were classified into CYP2A and CYP3A subfamilies, respectively. The content of the protein immunoreactive with anti-P450 CMLc in cynomolgus monkeys was decreased by the administration of aztreonam. P450 CMLd was one of CYP2C enzymes and was the S-mephenytoin 4'-hydroxylase in cynomolgus monkeys. The cDNA coding for monkey CYP2C (reffered to as CYP2C37) was isolated and was expressed in yeast. The expressed protein act as S-mephenytoin 4'-hydroxylase.
