Petroni A, Bertagnolio B, La Spada P, Blasevich M, Papini N, Govoni S, Rimoldi M, Galli C
Institute of Pharmacological Sciences, University of Milan, Italy.
Neurosci Lett. 1998 Jul 10;250(3):145-8. doi: 10.1016/s0304-3940(98)00467-4.
The beta-oxidation of [3H] arachidonic acid (AA; 20:4 n-6) and the conversion of [1-14C]eicosapentaenoic acid (EPA, 20:5 n-3) to docosahexaenoic acid (DHA, 22:6 n-3) have been studied in skin fibroblasts from patients with inherited peroxisomal diseases, such as Zellweger (ZW) and X-linked adrenoleukodystrophy (X-ALD), from patients with Alzheimer's disease (AD), a non-inherited neuropathology, and from controls. EPA is not converted to DHA, while there is enhanced formation of the intermediate product 22:5 n-3 in ZW, when compared to X-ALD, AD and controls. We also confirmed that AA is not beta-oxidized to 4,7,10-hexadecatrienoic acid (16:3), a metabolite produced by peroxisomes, while being more effectively converted to the elongation product 22:4, in ZW, in comparison to X-ALD, AD and controls. The data demonstrate a defect in DHA synthesis and in AA beta-oxidation, and the occurrence of associated adaptative modifications in the metabolism of these long chain PUFA, in three Italian ZW patients.
对患有遗传性过氧化物酶体疾病（如脑肝肾综合征（ZW）和X连锁肾上腺脑白质营养不良（X-ALD））的患者、患有非遗传性神经病理学疾病阿尔茨海默病（AD）的患者以及对照组的皮肤成纤维细胞中[3H]花生四烯酸（AA；20:4 n-6）的β氧化和[1-14C]二十碳五烯酸（EPA，20:5 n-3）向二十二碳六烯酸（DHA，22:6 n-3）的转化进行了研究。与X-ALD、AD和对照组相比，ZW患者中EPA不能转化为DHA，而中间产物22:5 n-3的生成增强。我们还证实，与X-ALD、AD和对照组相比，ZW患者中AA不能β氧化为过氧化物酶体产生的代谢产物4,7,10-十六碳三烯酸（16:3），而更有效地转化为延长产物22:4。数据表明，三名意大利ZW患者存在DHA合成和AAβ氧化缺陷，以及这些长链多不饱和脂肪酸代谢中相关适应性修饰的发生。
