Utilization of sterol carrier protein-2 by phytanoyl-CoA 2-hydroxylase in the peroxisomal α oxidation of phytanic acid

被引：46

作者：

Mukherji, M

Kershaw, NJ

Schofield, CJ

Wierzbicki, AS

Lloyd, MD

机构：

[1] Oxford Ctr Mol Sci, Dyson Perrins Lab, Oxford OX1 3QY, England

[2] Kings Guys & St Thomas Med Sch, Dept Chem Pathol, London SE1 7EH, England

[3] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England

来源：

CHEMISTRY & BIOLOGY | 2002年 / 9卷 / 05期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

D O I：

10.1016/S1074-5521(02)00139-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：597 / 605

页数：9

共 61 条

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