Identification of the cytochrome P450 enzymes responsible for the omega-hydroxylation of phytanic acid.
Patients suffering from Refsum disease have a defect in the alpha-oxidation pathway which results in the accumulation of phytanic acid in plasma and tissues. Our previous studies have shown that phytanic acid is also a substrate for the omega-oxidation pathway. With the use of specific inhibitors we now show that members of the cytochrome P450 (CYP450) family 4 class are responsible for phytanic acid omega-hydroxylation. Incubations with microsomes containing human recombinant CYP450s (Supersomes) revealed that multiple CYP450 enzymes of the family 4 class are able to omega-hydroxylate phytanic acid with the following order of efficiency: CYP4F3A>CYP4F3B>CYP4F2>CYP4A11.
Komen
J C
JC
Department of Clinical Chemistry, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Wanders
R J A
RJ
D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism*; D004050:Ditiocarb / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D006900:Hydroxylation; D007700:Kinetics; D008862:Microsomes, Liver / Q000201:enzymology; D010831:Phytanic Acid / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D065607:Cytochrome P-450 Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D011994:Recombinant Proteins; D010831:Phytanic Acid; C047008:17-octadecynoic acid; D003577:Cytochrome P-450 Enzyme System; D004050:Ditiocarb