QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Choudhary, D. Articles by Schenkman, J. B. Search for Related Content PubMed PubMed Citation Articles by Choudhary, D. Articles by Schenkman, J. B.

METABOLISM OF RETINOIDS AND ARACHIDONIC ACID BY HUMAN AND MOUSE CYTOCHROME P450 1B1

Department of Pharmacology (D.C., I.J., I.S., J.B.S.) and Molecular Ophthalmic Genetics Laboratory, Department of Surgery (M.S.), University of Connecticut Health Center, Farmington, Connecticut

The cytochrome P450 family 1 (CYP1) is considered to be one of the xenobiotic-metabolizing enzyme families and is responsible for oxidative metabolism of polycyclic aromatic hydrocarbons. For example, mouse Cyp1b1 was originally identified as the enzyme responsible for oxidative metabolism of 7,12-dimethylbenz()anthracene (DMBA). A comparison of the kinetics of this metabolism by mouse and human CYP1B1 orthologs revealed the mouse enzyme to have a more favorable metabolism of DMBA, with a catalytic efficiency ratio (CER) of 0.23. However, CYP1 enzymes are also capable of metabolism of endobiotics, and in the present study, the metabolism of retinoids and lipid endobiotics by human CYP1B1 and mouse Cyp1b1 orthologs was compared. Both hemoproteins oxidized retinol to retinal and retinal to retinoate, but did not oxidize retinoate. The CYP1B1 to Cyp1b1 CERs were 13 and 26 for the two steps, respectively; the Cyp1b1 K_m(app) values for retinoids were 20-fold higher. Human family 1 cytochromes P450 had unique regional specificities for arachidonate oxidation: the major metabolites of CYP1A1, CYP1A2, and CYP1B1 were 75% terminal hydroxyeicosatetraenoic fatty acids (HETEs), 52% epoxyeicosatrienoic fatty acids (EETs), and 54% mid-chain HETEs, respectively. CYP1A1 and CYP1B1 K_m(app) values for arachidonate were about 30 µM, whereas CYP1A2 K_m(app) was 95 µM. The major metabolites of arachidonic acid by Cyp1b1 were EETs (50%) and midchain HETEs (37%). The mouse ortholog had a CER for metabolite production of 64 due to a K_m(app) of 0.5 mM for arachidonate.

This article has been cited by other articles:

				D. E. Conway, Y. Sakurai, D. Weiss, J. D. Vega, W. R. Taylor, H. Jo, S. G. Eskin, C. B. Marcus, and L. V. McIntire Expression of CYP1A1 and CYP1B1 in human endothelial cells: regulation by fluid shear stress Cardiovasc Res, March 1, 2009; 81(4): 669 - 677. [Abstract] [Full Text] [PDF]

				R. De Caterina and R. Madonna Cytochromes CYP1A1 and CYP1B1: new pieces in the puzzle to understand the biomechanical paradigm of atherosclerosis Cardiovasc Res, March 1, 2009; 81(4): 629 - 632. [Full Text] [PDF]

				D. W. Nebert and C. L. Karp Endogenous Functions of the Aryl Hydrocarbon Receptor (AHR): Intersection of Cytochrome P450 1 (CYP1)-metabolized Eicosanoids and AHR Biology J. Biol. Chem., December 26, 2008; 283(52): 36061 - 36065. [Full Text] [PDF]

				B. N. M. Zordoky, M. E. Aboutabl, and A. O. S. El-Kadi Modulation of Cytochrome P450 Gene Expression and Arachidonic Acid Metabolism during Isoproterenol-Induced Cardiac Hypertrophy in Rats Drug Metab. Dispos., November 1, 2008; 36(11): 2277 - 2286. [Abstract] [Full Text] [PDF]

				D. Choudhary, I. Jansson, K. Rezaul, D. K. M. Han, M. Sarfarazi, and J. B. Schenkman Cyp1b1 Protein in the Mouse Eye during Development: An Immunohistochemical Study Drug Metab. Dispos., June 1, 2007; 35(6): 987 - 994. [Abstract] [Full Text] [PDF]

				D. Chambers, L. Wilson, M. Maden, and A. Lumsden RALDH-independent generation of retinoic acid during vertebrate embryogenesis by CYP1B1 Development, April 1, 2007; 134(7): 1369 - 1383. [Abstract] [Full Text] [PDF]

				S. Diani-Moore, F. Papachristou, E. Labitzke, and A. B. Rifkind INDUCTION OF CYP1A AND CYP2-MEDIATED ARACHIDONIC ACID EPOXYGENATION AND SUPPRESSION OF 20-HYDROXYEICOSATETRAENOIC ACID BY IMIDAZOLE DERIVATIVES INCLUDING THE AROMATASE INHIBITOR VOROZOLE Drug Metab. Dispos., August 1, 2006; 34(8): 1376 - 1385. [Abstract] [Full Text] [PDF]

				S. X. Yang, R. M. Simon, A. R. Tan, D. Nguyen, and S. M. Swain Gene Expression Patterns and Profile Changes Pre- and Post-Erlotinib Treatment in Patients with Metastatic Breast Cancer Clin. Cancer Res., September 1, 2005; 11(17): 6226 - 6232. [Abstract] [Full Text] [PDF]