CYP4 Isoform Specificity in the ω-Hydroxylation of Phytanic Acid, a Potential Route to Elimination of the Causative Agent of Refsum’s Disease

• DOI: 10.1124/jpet.106.104976
• Publication Date: 2006-05-18T00:44:10Z
• Authors: Fengyun Xu; Valerie Y. Ng; Deanna L. Kroetz; Paul R. Ortiz de ...
• Keywords: Phytanic acid; Phytol; Hydroxylation

The saturated C20 isoprenoid phytanic acid is physiologically derived from phytol released in the degradation of chlorophyll. presence a C-3 methyl group this substrate blocks normal β-oxidation, so primarily occurs by initial peroxisomal α-oxidation to shift register group. However, individuals with Refsum9s disease are genetically deficient required phytanoyl-CoA α-hydroxylase and suffer neurological pathologies caused accumulation acid. Recent work has shown that can also be catabolized pathway initiated ω-hydroxylation hydrocarbon chain, followed oxidation alcohol conventional β-oxidation. enzymes responsible for have not been identified. In study, we determined activities all rat human CYP4A two CYP4F enzymes, respect Furthermore, ability ω-hydroxylate elevated microsomes rats pretreated clofibrate. results support possible role CYP4 enzyme elevation elimination patients.