Cytochrome P450 reconstitution systems.

Abstract

AbstractMultiple forms of cytochrome P450 (CYP) exist in liver mrcrosomes and these P450 forms have been shown to play important roles in the oxidation of structurally diverse xenobrotrc chemicals such as drugs, toxic chemicals, and carcinogens, as well as endobiottc chemicals including steroids, fatty acids, fat-soluble vitamins, and prostaglandins (1). Major cytochrome P450 enzymes in human liver microsomes identified to date mclude CYPlA2,2A6,2B6,2C8, 2C9, 2C19, 2D6, 2E1, 3A4, and 3A5 (and 3A7 in fetal livers) (2). CYPlAl and 1 B 1 have also been reported to be involved in the oxidation of drugs, toxic chemicals, and carcinogens in extrahepatic tissues (3). There are large mtermdividual variations in the amounts of each of these cytochrome P450 enzymes, and these variations are considered to be one of the major factors m contributing to differences in susceptibilities of humans towards actions and toxicities of drugs, toxic chemicals, and carcmogens (2). Recently, in order to investigate the consequences for enzymic actrvity of genetic polymorphisms of individual cytochrome P450 enzymes in humans, many investigators have carried out studies with cytochrome P450 proteins purified from heterologous organisms in which native and modified human cytochrome P450 cDNAs have been introduced (4)KeywordsLiver MicrosomeHuman Liver MicrosomeCytochrome P450 EnzymeSodium CholateCytochrome P450 ReductaseThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.