Phytanic acid (PA) is an epimeric metabolite of the isoprenoid side chain of chlorophyll. Owing to the presence of its epimeric β-methyl group, PA cannot be metabolized by β-oxidation. Instead, it is metabolized in peroxisomes via α-oxidation to give pristanic acid, which is then oxidized by β-oxidation. PhyH (phytanoyl-CoA 2-hydroxylase, also known as PAHX), an Fe(II) and 2OG (2-oxoglutarate) oxygenase, catalyses hydroxylation of phytanoyl-CoA. Mutations of PhyH ablate its role in α-oxidation, resulting in PA accumulation and ARD (adult Refsum's disease). The structure and function of PhyH is discussed in terms of its clinical importance and unusual selectivity. Most point mutations of PhyH causing ARD cluster in two distinct groups around the Fe(II)- and 2OG-binding sites. Therapaeutic possibilities for the treatment of Refsum's disease involving PhyH are discussed.

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