title: Utilization of sterol carrier protein-2 by phytanoyl-CoA 2-hydroxylase in the peroxisomal alpha oxidation of phytanic acid.
abstract: Since it possesses a 3-methyl group, phytanic acid is degraded by a peroxisomal alpha-oxidation pathway, the first step of which is catalyzed by phytanoyl-CoA 2-hydroxylase (PAHX). Mutations in human PAHX cause phytanic acid accumulations leading to Adult Refsum's Disease (ARD), which is also observed in a sterol carrier protein 2 (SCP-2)-deficient mouse model. Phytanoyl-CoA is efficiently 2-hydroxylated by PAHX in vitro in the presence of mature SCP-2. Other straight-chain fatty acyl-CoA esters were also 2-hydroxylated and the products isolated and characterized. Use of SCP-2 increases discrimination between straight-chain (e.g., hexadecanoyl-CoA) and branched-chain (e.g., phytanoyl-CoA) substrates by PAHX. The results explain the phytanic acid accumulation in the SCP-2-deficient mouse model and suggest that some of the common symptoms of ARD and other peroxisomal diseases may arise in part due to defects in SCP-2 function caused by increased phytanic acid levels.
authors.affiliation: The Oxford Centre for Molecular Science, The Dyson Perrins Laboratory, South Parks Road, OX1 3QY, Oxford, United Kingdom.
authors.forename: Mridul
authors.initials: M
authors.lastname: Mukherji
authors.forename: Nadia J
authors.initials: NJ
authors.lastname: Kershaw
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schofield
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Wierzbicki
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Lloyd
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D006801:Humans; D006900:Hydroxylation; D007656:Ketoglutaric Acids / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000378:metabolism*; D010831:Phytanic Acid / Q000737:chemistry / Q000378:metabolism*; D010940:Plant Proteins; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000214:Acyl Coenzyme A; D002352:Carrier Proteins; D007656:Ketoglutaric Acids; D010940:Plant Proteins; C072087:sterol carrier proteins; D010831:Phytanic Acid; D006899:Mixed Function Oxygenases; C102623:PHYH protein, human; C491170:Phyh protein, mouse