Identification of the cytochrome P450 enzymes responsible for the ω-hydroxylation of phytanic acid

• Published in: FEBS letters Vol. 580; no. 16; pp. 3794 - 3798
• Main Authors: Komen, J.C., Wanders, R.J.A.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 10.07.2006
• Subjects: 17-octadecynoic acid; 17-ODYA; adult Refsum disease; ARD; Branched-chain fatty acid; CYP450; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System - drug effects; Cytochrome P-450 Enzyme System - metabolism; Cytochrome P450; DDC; diethyldithiocarbamate; Ditiocarb - pharmacology; Fatty Acids, Unsaturated - pharmacology; Humans; Hydroxylation; Kinetics; Microsomes, Liver - enzymology; Phytanic acid; Phytanic Acid - metabolism; Recombinant Proteins - metabolism; Refsum disease; ω-Hydroxylation; ω-Oxidation; ω-Oxidation; DDC; ARD; CYP450; Cytochrome P450; ω-Hydroxylation; Phytanic acid; Branched-chain fatty acid; Refsum disease; 17-ODYA
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2006.05.069

Patients suffering from Refsum disease have a defect in the α-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 ω-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 ω-hydroxylation. Incubations with microsomes containing human recombinant CYP450s (Supersomes™) revealed that multiple CYP450 enzymes of the family 4 class are able to ω-hydroxylate phytanic acid with the following order of efficiency: CYP4F3A > CYP4F3B > CYP4F2 > CYP4A11.