Hydroxylation of fatty acids by microsomal and reconstituted cytochrome P450 2B1.
Understanding the mechanisms by which cytochrome(s) P450 (CYP) discriminate good from poor substrates, and orient them for highly regio- and stereoselective oxidation, has considerable intrinsic and practical importance. Here we present results of a study of fatty acid hydroxylation by CYP2B1 in a reconstituted system and in microsomes from phenobarbital-pretreated rats. The results indicate that 2B1 prefers decanoic acid as the optimum fatty acid substrate (among C(8)-C(16)) and that it hydroxylates all positions five or more methylene groups distant from the carboxylate carbon. That hydroxylation does not occur at carbon atoms closer to the carboxyl group than the C(6) position suggests that these carbons may not reach the ferryl oxygen because the carboxyl group is anchored to a specific site at a fixed distance from the heme iron.
Alterman
Michail A
MA
Biochemical Research Service Laboratory, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045-7582, USA. malterman@ku.edu
Hanzlik
Robert P
RP
D000818:Animals; D020134:Catalytic Domain; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D006900:Hydroxylation; D008862:Microsomes, Liver / Q000378:metabolism*; D008968:Molecular Conformation; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D013379:Substrate Specificity
D005227:Fatty Acids; D019362:Cytochrome P-450 CYP2B1; D010634:Phenobarbital