High impact information on Cyp2c29

• This computational prediction was experimentally confirmed by showing that the rate-limiting step in biotransformation of warfarin to its 7-hydroxylated metabolite was inhibited by tolbutamide, a Cyp2c isoform-specific substrate, and that this transformation was mediated by expressed recombinant Cyp2c29 [1].
• After quantification of warfarin and nine of its metabolites in plasma from 13 inbred mouse strains, we correlated strain-specific differences in 7-hydroxywarfarin accumulation with genetic variation within a chromosomal region encoding cytochrome P450 2C (Cyp2c) enzymes [1].
• Herein, we used in vivo and in vitro gene reporter assays of the Cyp2c29 promoter to delineate the phenytoin-response activity to a phenytoin-responsive module located at -1371 kb upstream of the Cyp2c29 translation start site [2].
• The constitutive active/androstane receptor regulates phenytoin induction of Cyp2c29 [2].
• In this report, we describe the organization of the mouse Cyp2c locus, which contains 15 genes and four pseudogenes, all of which are located in a 5.5-megabase region on chromosome 19 [3].

Biological context of Cyp2c29

• The deduced amino acid sequence of CYP2C29 exhibited 83% identity with that of the rat CYP2C7 and had an N-terminal sequence identical to that of P-450 MUT-2, a microsomal aldehyde oxygenase [4].
• P450 MUT-2 exhibited aldehyde oxygenase activity for 11-oxo-delta 8-TH, 11-oxo-delta 9-THC, 11-oxo-cannabinol (11-oxo-CBN) and 9-anthraldehyde together with high activity for the hydroxylation of cannabinoids at the 11-position [5].
• Sex difference in hepatic microsomal aldehyde oxygenase activity in different strains of mice [6].

Anatomical context of Cyp2c29

• No inhibition of SR 4233 reduction was seen with erythromycin or cyclosporin A which act as substrates/inhibitors for Cyp3a-type enzymes, but inhibition was seen with p-nitrophenol and tolbutamide which are substrates for Cyp2el- and Cyp2c-type enzymes, respectively (11% and 25% inhibition in induced microsomes) [7].
• A Cyp2c29 immunorelated P450 isoform was expressed in nearly all astrocytes in culture [8].
• After induction with phenobarbital and phenytoin, a new reaction sequence catalyzed by Cyp2c29 was identified in mouse liver microsomes [9].

Associations of Cyp2c29 with chemical compounds

• Immunoinhibition studies with epitope specific monoclonal antibodies were consistent with the major involvement of phenobarbitone- and steroid-inducible products of the Cyp2b and Cyp2c subfamilies [7].
• Hepatic CYP2C29 mRNA was induced by phenytoin in wild-type but not in CAR-null mice, indicating that constitutive active or androstane receptor (CAR) regulates phenytoin-induced transcription of the Cyp2c29 gene [2].
• Cyp2c29-dependent 6-demethylation of scoparone resulted in the formation of isoscopoletin, an intermediate which is susceptible to further oxidation [9].
• Analysis of NH2-terminal sequence suggests that the isozyme is a member of the P450 2C gene subfamily [5].
• Effects of LPS administration on mouse hepatic P450 proteins (probed using rat P450 2C, 3A, 4A, and 2E antibodies) were consistent with mRNA results in most cases [10].

Other interactions of Cyp2c29

• In contrast, expression of Cyp2c22, Cyp2c29, and Cyp2c40 was reduced in diabetic, but normal in insulin resistant mice [11].
• A cytochrome P450 isozyme having aldehyde oxygenase activity plays a major role in metabolizing cannabinoids by mouse hepatic microsomes [5].

Analytical, diagnostic and therapeutic context of Cyp2c29

• Immunoprecipitation of microsomal protein with antibodies raised against either P450 2C or 3A revealed that approximately equal amounts of [14C]-CBD were bound to each of these P450s after CBD-mediated inactivation [12].

References