Ketoconazole and other imidazole derivatives are potent inhibitors of peroxisomal phytanic acid α‐oxidation

FEBS Letters

Khan, Mushfiquddin¹  Smith, Brian T.¹  Singh, Inderjit¹  Pahan, Kalipada¹ 

[1] Department of Pediatrics, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29525, USA

关键词: Phytanic acid;    Peroxisome (human);    Antimycotics;    Cytochrome P-450;   

DOI  :  10.1016/0014-5793(95)01341-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The imidazole antimycotics like ketoconazole, clotrimazole, bifonazole, miconazole and CO, known as powerful inhibitors of cytochrome P-450, are potent inhibitors of peroxisomal phytanic acid α-oxidation to pristanic acid suggesting the possible involvement of the cytochrome P-450 mono-oxygenase system in this oxidation. In contrast to the inhibition of the oxidation of [1-¹⁴C]phytanic acid, [1-¹⁴C]phytanoyl-CoA and [(2,3)-³H]phytanic acid, these drugs and CO have no effect on the oxidation of [1-¹⁴C]α-hydroxy phytanic acid indicating that these drugs and CO inhibit only the α-hydroxylation of phytanic acid. These studies using purified peroxisomes from liver and cultured human skin fibroblasts and Hep G2 cells clearly demonstrate that α-hydroxylation, an intermediate step in the α-oxidation of phytanic acid found to be impaired in Refsum Disease, is mediated by cytochrome P-450 containing enzyme.

【 授权许可】

Unknown