DISORDERS OF MITOCHONDRIAL LONG-CHAIN FATTY-ACID OXIDATION
DISORDERS OF MITOCHONDRIAL LONG-CHAIN FATTY-ACID OXIDATION
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DOI：
10.1007/bf00710058
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发表时间：
1995-01-01
影响因子：
4.2
通讯作者：
POLLITT, RJ
中科院分区：
文献类型：
--
作者：
POLLITT, RJ
长链脂肪酸的氧化需要位于线粒体膜内或线粒体膜上的一系列酶。其中包括肉碱棕榈酰转移酶 I 和 II、肉碱-酰基肉碱转位酶以及新发现的超长链酰基辅酶 A 脱氢酶和线粒体三功能蛋白。最后两个链缩短的酰基辅酶A酯达到可以转移到线粒体基质内更可溶的中链和短链特异性酶的程度。长链脂肪酸氧化疾病表现出相当相似的临床和生化特征，尽管在不同的情况下侧重点不同。患有严重缺陷的患者通常早期会出现低酮性低血糖和肝功能受损的急性发作，或者出现心肌病或心律失常。在较轻微的变异中，伴有间歇性肌红蛋白尿的骨骼肌病会在晚年发生。 3-羟酰辅酶A脱氢酶缺乏在导致周围神经病变和色素性视网膜炎方面并不常见。治疗方法是避免禁食并用中链甘油三酯替代正常膳食脂肪，中链脂肪酸以不依赖肉碱的方式进入线粒体并绕过螺旋的长链部分。诊断最终必须基于所涉及酶的直接测定，但初步指标可能来自血浆中肉碱和中间代谢物的测定、尿有机酸分析以及淋巴细胞或培养成纤维细胞的放射性同位素筛查测定。
The oxidation of long-chain fatty acids requires a series of enzymes which are located in or on the mitochondrial membranes. These include carnitine palmitoyltransferases I and II, a carnitine-acylcarnitine translocase and, newly discovered, very long-chain acyl-CoA dehydrogenase and the mitochondrial trifunctional protein. These last two chain-shorten acyl-CoA esters to the point where they can be transferred to the more soluble medium- and short-chain-specific enzymes within the mitochondrial matrix. The disorders of long-chain fatty acid oxidation show a rather similar range of clinical and biochemical features, though with different emphasis in the different conditions. Patients with severe defects usually present early with acute attacks of hypoketotic hypoglycaemia and impaired liver function, or with cardiomyopathy or cardiac arrhythmia. In milder variants, skeletal myopathy with intermittent myoglobinuria develops later in life. 3-Hydroxyacyl-CoA dehydrogenase deficiency is unusual in producing peripheral neuropathy and retinitis pigmentosa. Treatment is based on the avoidance of fasting and replacement of normal dietary fat by medium-chain triglyceride, the medium-chain fatty acids entering the mitochondria in a carnitine-independent manner and bypassing the long-chain part of the spiral. Diagnosis must ultimately be based on direct assay of the enzyme involved, but preliminary indicators may come from determination of carnitine and intermediate metabolites in plasma, urinary organic acid profiling, and radioisotopic screening assays with lymphocytes or cultured fibroblasts.