Poulos A, Beckman K, Johnson D W, Paton B C, Robinson B S, Sharp P, Usher S, Singh H
Department of Chemical Pathology, Adelaide Medical Centre for Women and Children, South Australia.
Adv Exp Med Biol. 1992;318:331-40. doi: 10.1007/978-1-4615-3426-6_30.
Fatty acids with from 24 to 28 carbon atoms (very long-chain fatty acids, VLCFA) are present in small amounts in all mammalian tissues. Even longer chain fatty acids with from 30 to 38 carbon atoms (ultra-long-chain fatty acids, ULCFA) are found in certain specialized tissues including retina, brain, and spermatozoa. In patients with inherited defects in peroxisomal structure and/or function, there is an accumulation of VLCFA in most tissues, while VLCFA and ULCFA levels are increased in brain. The most pronounced changes occur in those patients who have defects in peroxisomal assembly (Zellweger syndrome, infantile Refsum's disease, and neonatal adrenoleukodystrophy). In the brain of these individuals, ULCFA are distributed largely in molecular species of phosphatidylcholine with penta-, hexa-, and heptaenoic acids. In contrast, patients with X-linked adrenoleukodystrophy have increased levels of phosphatidylcholine with monoenoic rather than polyenoic ULCFA. A defect in a peroxisomal VLCFA CoA synthetase or ligase has been reported for these patients, but assembly of their peroxisomes is apparently normal. We speculate that ULCFA are normal products of carbon chain elongation. We have confirmed this by demonstrating the elongation of [1-14C]hexacosatetraenoic acid (26:4n-6) by rat brain in vivo to a series of longer chain tetraenoic acids with carbon chain lengths up to 34. Elongation to ULCFA can occur as well in non-neural tissues as shown by detection of labeled saturated and monoenoic fatty acids with up to 32 carbon atoms after incubation of normal and Zellweger syndrome fibroblasts with [2-14C] acetate. Increased labeling of VLCFA and ULCFA is observed in cells from patients with peroxisomal disorders. Our data suggest that ULCFA with up to at least 32 carbon atoms are formed normally, as a part of the elongation process in most mammalian tissues, and that control of carbon chain elongation is a major function of peroxisomes. Impairment of this function as occurs in peroxisomal disease results in the accumulation of VLCFA and ULCFA. The relative enrichment in normal tissues of ULCFA such as 32:6n-3 in ram and bull spermatozoa and 36:4n-6 in human and rat brain suggests a probable physiological role for this class of fatty acids in these tissues.
含24至28个碳原子的脂肪酸（极长链脂肪酸，VLCFA）在所有哺乳动物组织中含量甚微。含30至38个碳原子的更长链脂肪酸（超长链脂肪酸，ULCFA）则存在于某些特殊组织中，包括视网膜、脑和精子。在过氧化物酶体结构和/或功能存在遗传性缺陷的患者中，大多数组织中VLCFA会蓄积，而脑中VLCFA和ULCFA水平会升高。过氧化物酶体组装存在缺陷的患者（泽尔韦格综合征、婴儿型雷夫叙姆病和新生儿肾上腺脑白质营养不良）变化最为显著。在这些个体的脑中，ULCFA主要分布于含有五烯酸、六烯酸和七烯酸的磷脂酰胆碱分子种类中。相比之下，X连锁肾上腺脑白质营养不良患者的磷脂酰胆碱中，单烯而非多烯ULCFA水平升高。据报道，这些患者存在过氧化物酶体VLCFA辅酶A合成酶或连接酶缺陷，但其过氧化物酶体组装显然正常。我们推测ULCFA是碳链延长的正常产物。我们通过证明大鼠脑在体内将[1-14C]二十六碳四烯酸（26:4n-6）延长为一系列碳链长度达34的更长链四烯酸，证实了这一点。正常和泽尔韦格综合征成纤维细胞与[2-14C]乙酸孵育后，检测到含32个碳原子的标记饱和脂肪酸和单烯脂肪酸，这表明非神经组织中也能发生向ULCFA的延长。过氧化物酶体疾病患者的细胞中，VLCFA和ULCFA的标记增加。我们的数据表明，至少含32个碳原子的ULCFA是在大多数哺乳动物组织的延长过程中正常形成的，过氧化物酶体的主要功能之一是控制碳链延长。过氧化物酶体疾病中发生的这种功能损害会导致VLCFA和ULCFA蓄积。正常组织中ULCFA的相对富集，如公羊和公牛精子中的32:6n-3以及人和大鼠脑中的36:4n-6，表明这类脂肪酸在这些组织中可能具有生理作用。
