Verhoeven N M, Wanders R J, Poll-The B T, Saudubray J M, Jakobs C
Department of Clinical Chemistry, Free University Hospital, Amsterdam, The Netherlands.
J Inherit Metab Dis. 1998 Oct;21(7):697-728. doi: 10.1023/a:1005476631419.
The branched-chain fatty acid phytanic acid is a constituent of the diet, present in diary products, meat and fish. Degradation of this fatty acid in the human body is preceded by activation to phytanoyl-CoA and starts with one cycle of alpha-oxidation. Intermediates in this pathway are 2-hydroxy-phytanoyl-CoA and pristanal; the product is pristanic acid. After activation, pristanic acid is degraded by peroxisomal beta-oxidation. Several disorders have been described in which phytanic acid accumulates, in some cases in combination with pristanic acid. In classical Refsum disease, the enzyme that converts phytanoyl-CoA into 2-hydroxyphytanoyl-CoA--phytanoyl-CoA hydroxylase--is deficient, resulting in highly elevated levels of phytanic acid in blood and tissues. Also in rhizomelic chondrodysplasia punctata, phytanic acid accumulates, owing to a deficiency in the peroxisomal import of proteins with a peroxisomal targeting sequence type 2. In patients affected with generalized peroxisomal disorders, degradation of both phytanic acid and pristanic acid is impaired owing to absence of functional peroxisomes. In bifunctional protein deficiency, the disturbed oxidation of pristanic acid results in elevated levels of this fatty acid and a secondary elevation of phytanic acid. In addition, several variant peroxisomal disorders with unknown aetiology have been described in which phytanic acid and/or pristanic acid accumulate. This review describes the discovery of phytanic acid and pristanic acid and the initial attempts to elucidate the origins and fates of these fatty acids. The current knowledge on the alpha-oxidation and beta-oxidation of these branched-chain fatty acids is summarized. The disorders in which phytanic acid and/or pristanic acid accumulate are described and some remarks are made on the pathogenic mechanisms of elevated levels of phytanic acid and pristanic acid.
支链脂肪酸植烷酸是饮食中的一种成分，存在于乳制品、肉类和鱼类中。这种脂肪酸在人体内的降解过程首先是被激活为植烷酰辅酶A，然后从一轮α-氧化开始。该途径的中间产物是2-羟基植烷酰辅酶A和降植烷醛；产物是降植烷酸。激活后，降植烷酸通过过氧化物酶体β-氧化进行降解。已经描述了几种植烷酸积累的疾病，在某些情况下还伴有降植烷酸的积累。在典型的雷夫叙姆病中，将植烷酰辅酶A转化为2-羟基植烷酰辅酶A的酶——植烷酰辅酶A羟化酶——缺乏，导致血液和组织中植烷酸水平大幅升高。在肢根型点状软骨发育不良中，由于缺乏带有2型过氧化物酶体靶向序列的蛋白质的过氧化物酶体导入，植烷酸也会积累。在患有全身性过氧化物酶体疾病的患者中，由于缺乏功能性过氧化物酶体，植烷酸和降植烷酸的降解均受到损害。在双功能蛋白缺乏症中，降植烷酸氧化紊乱导致这种脂肪酸水平升高以及植烷酸继发性升高。此外，还描述了几种病因不明的过氧化物酶体疾病变体，其中植烷酸和/或降植烷酸会积累。本综述描述了植烷酸和降植烷酸的发现以及阐明这些脂肪酸的来源和去向的初步尝试。总结了目前关于这些支链脂肪酸α-氧化和β-氧化的知识。描述了植烷酸和/或降植烷酸积累的疾病，并对植烷酸和降植烷酸水平升高的致病机制作了一些说明。
