title: Peroxisomal disorders affecting phytanic acid alpha-oxidation: a review.
abstract: Peroxisomes are involved in the synthesis and degradation of complex fatty acids. They contain enzymes involved in the alpha-, beta- and omega-oxidation pathways for fatty acids. Investigation of these pathways and the diseases associated with mutations in enzymes involved in the degradation of phytanic acid have led to the clarification of the pathophysiology of Refsum's disease, rhizomelic chondrodysplasia and AMACR (alpha-methylacyl-CoA racemase) deficiency. This has highlighted the role of an Fe(II)- and 2-oxoglutarate-dependent oxygenases [PhyH (phytanoyl-CoA 2-hydroxylase), also known as PAHX], thiamin-dependent lyases (phytanoyl-CoA lyase) and CYP (cytochrome P450) family 4A in fatty acid metabolism. The differential regulation and biology of these pathways is suggesting novel ways to treat the neuro-ophthalmological sequelae of Refsum's disease. More recently, the discovery that AMACR and other peroxisomal beta-oxidation pathway enzymes are highly expressed in prostate and renal cell cancers has prompted active investigation into the role of these oxidation pathways and the peroxisome in the progression of obesity- and insulin resistance-related cancers.
authors.affiliation: Department of Chemical Pathology, St. Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K. anthony.wierzbicki@kcl.ac.uk
authors.forename: A S
authors.initials: AS
authors.lastname: Wierzbicki
mesh_terms: D006801:Humans; D010084:Oxidation-Reduction; D018901:Peroxisomal Disorders / Q000378:metabolism*; D010831:Phytanic Acid / Q000378:metabolism*; D012035:Refsum Disease / Q000235:genetics / Q000378:metabolism / Q000628:therapy
chemical_list: D010831:Phytanic Acid