Phytanic acid activation in rat liver peroxisomes is catalyzed by long-chain acyl-CoA synthetase.

摘要: In Refsum disease, disorders of peroxisome biogenesis, and rhizomelic chondrodysplasia punctata, pathological accumulation phytanic acid results from impaired alpha-oxidation this branched-chain fatty acid. Previous studies laboratory indicated that activation to its CoA derivative precedes in peroxisomes. It was reported reaction is catalyzed by a unique phytanoyl-CoA synthetase human We wanted determine whether rats required long-chain acyl-CoA (LCS), very (VLCS), or different enzyme. To test directly LCS could activate acid, rat liver cDNA encoding enzyme transcribed translated vitro. The expressed had both activity (assayed with palmitic C16: 0) activity; VLCS lignoceric C24: not detectable. ratio synthetized palmitoyl-CoA for vitro (approximately 205) higher than observed peroxisomes isolated (5-10%), suggesting the contained sufficient phytanoyl-Coa account all intact Further experiments were carried out verify activated Attempts separate chromatography on several matrices unsuccessful. Preparative isoelectric focusing revealed indistinguishable points. Phytanoyl-CoA inhibited unlabeled but Heat treatment inactivated activities at similar rates. 5,8,11,14-Eicosatetraynoic parallel dose-dependent manner, whereas affected. These data support our conclusion LCS, an known be present peroxisomal membranes, has activity.