Leukotriene B4 omega-side chain hydroxylation by CYP4F5 and CYP4F6. Arch Biochem Biophys 2003 Apr 01;412(1):34-41
Date
03/21/2003Pubmed ID
12646265DOI
10.1016/s0003-9861(03)00030-4Scopus ID
2-s2.0-0037376494 (requires institutional sign-in at Scopus site) 25 CitationsAbstract
Leukotriene B(4) (LTB(4)) is a lipid mediator that plays an important role in inflammation. Metabolism of LTB(4) by cytochrome P450 (CYP) enzymes belonging to the CYP4F subfamily is considered to be of importance for the regulation of inflammation. This study investigates LTB(4) metabolism by recombinant rat CYP4F5 and CYP4F6 expressed in a yeast system and by microsomes isolated from rat organs expressing CYP4F mRNA. CYP4F6 was found to convert LTB(4) into 19-hydoxy- and 18-hydroxy-LTB(4) with an apparent K(m) of 26 microM, and CYP4F5 was found to convert LTB(4) primarily into 18-hydroxy-LTB(4) with an apparent K(m) of 9.7 microM. The rate of formation of 18-hydroxy-LTB(4) by CYP4F5 was surprisingly high. At a substrate concentration of 30 microM, the rate of formation was about 15 nmol/min/mg microsomal protein, approximately 30 times faster than the reaction catalyzed by CYP4F6. Analysis of LTB(4) metabolism by microsomes isolated from various tissues from the rat suggests that CYP4F5 and CYP4F6 are active in the lung and to some extent in the brain, kidney, and testis. CYP4F5 and CYP4F6, due to their capacities to metabolize LTB(4), may play important roles in modulating inflammatory response in these organs.
Author List
Bylund J, Harder AG, Maier KG, Roman RJ, Harder DRMESH terms used to index this publication - Major topics in bold
AnimalsBlotting, Northern
Chromatography, Liquid
Cloning, Molecular
Cytochrome P-450 Enzyme System
Cytochrome P450 Family 4
DNA, Complementary
Dose-Response Relationship, Drug
Gas Chromatography-Mass Spectrometry
Kidney
Kinetics
Leukotriene B4
Male
Microsomes
Protein Binding
RNA, Messenger
Rats
Recombinant Proteins
Time Factors