Studies with purified subcellular organelles from rat liver indicate that nervonic acid (C24:1) is beta-oxidized preferentially in peroxisomes. Lack of effect by etomoxir, inhibitor of mitochondrial beta-oxidation, on beta-oxidation of lignoceric acid (C24:0), a peroxisomal function, and that of nervonic acid (24:1) compared to the inhibition of palmitic acid (16:0) oxidation, a mitochondrial function, supports the conclusion that nervonic acid is oxidized in peroxisomes. Moreover, the oxidation of nervonic and lignoceric acids was deficient in fibroblasts from patients with defects in peroxisomal beta-oxidation [Zellweger syndrome (ZS) and X-linked adrenoleukodystrophy (X-ALD)]. Similar to lignoceric acid, the activation and beta-oxidation of nervonic acid was deficient in peroxisomes isolated from X-ALD fibroblasts. Transfection of X-ALD fibroblasts with human cDNA encoding for ALDP (X-ALD gene product) restored the oxidation of both nervonic and lignoceric acids, demonstrating that the same molecular defect may be responsible for the abnormality in the oxidation of nervonic as well as lignoceric acid. Moreover, immunoprecipitation of activities for acyl-CoA ligase for both lignoceric acid and nervonic acid indicate that saturated and monoenoic very long chain (VLC) fatty acids may be activated by the same enzyme. These results clearly demonstrate that similar to saturated VLC fatty acids (e.g., lignoceric acid), VLC monounsaturated fatty acids (e.g., nervonic acid) are oxidized preferentially in peroxisomes and that this activity is impaired in X-ALD. In view of the fact that the oxidation of unsaturated VLC fatty acids is defective in X-ALD patients, the efficacy of dietary monoene therapy, "Lorenzo's oil," in X-ALD needs to be evaluated.

中文翻译：

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神经酸β-氧化在人和啮齿动物过氧化物酶体中的定位：Zellweger综合征和X连锁的肾上腺皮质营养不良的氧化受损。

用大鼠肝脏中纯化的亚细胞器进行的研究表明，神经过氧化物（C24：1）在过氧化物酶体中优先被β-氧化。线粒体β-氧化的抑制剂依托莫司对木质酸（C24：0），过氧化物酶体功能和神经酸（24：1）的β-氧化作用与棕榈酸的抑制作用相比缺乏作用（16： 0）氧化是一种线粒体功能，支持神经过氧化物在过氧化物酶体中被氧化的结论。此外，过氧化物酶体β-氧化[Zellweger综合征（ZS）和X-连锁性肾上腺皮质营养不良（X-ALD）]缺陷患者的成纤维细胞中神经酸和木质酸的氧化不足。与木质酸相似，神经酸的活化和β-氧化在从X-ALD成纤维细胞中分离出来的过氧化物酶体中也很缺乏。用编码ALDP的人类cDNA（X-ALD基因产物）转染X-ALD成纤维细胞可恢复神经酸和木质酸的氧化，表明相同的分子缺陷可能是神经氧化和木质酸氧化异常的原因。酸。此外，对于酰基辅酶A连接酶对于木质酸和​​神经酸的活性的免疫沉淀表明，饱和的和单烯的非常长链（VLC）脂肪酸可以被相同的酶激活。这些结果清楚地表明，与饱和VLC脂肪酸（例如，木质酸）相似，VLC单不饱和脂肪酸（例如，神经酸）在过氧化物酶体中被优先氧化，并且这种活性在X-ALD中被削弱。鉴于X-ALD患者中不饱和VLC脂肪酸的氧化存在缺陷，