Fatty Acid Oxidation Disorders
Fatty Acid Oxidation Disorders
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DOI：
10.1002/9780470015902.a0003067.pub2
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发表时间：
2001-04
期刊：
影响因子：
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通讯作者：
Padmini P. Polinati;Petra M Eskelin;T. Tyni
中科院分区：
文献类型：
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作者：
Padmini P. Polinati;Petra M Eskelin;T. Tyni
线粒体脂肪酸氧化（FAO）是在长期禁食、运动或代谢应激条件下提供能量的主要途径。许多影响这一代谢途径的遗传性疾病已被发现近二十年。线粒体FAO的缺陷特征性地表现为与婴儿期和儿童期的低血糖（低血糖）相关的严重代谢危机，并且也是肌肉疾病和心肌疾病的相对常见的原因。症状通常是偶发性的，通常与轻度病毒感染或禁食有关。治疗性干预通常能有效预防代谢失代偿，这强调了早期诊断的重要性。诊断测试，确定每种疾病的最佳饮食方案和产前筛查这些疾病可能会从根本上改变许多FAO疾病患者的预后不良。关键概念：脂肪酸可通过过氧化物酶体中的α-氧化、线粒体和过氧化物酶体中的β-氧化以及内质网中的ω-氧化来氧化。线粒体FAO是在长期禁食、运动或代谢应激条件下提供能量的主要途径。单个β-氧化循环由一系列四个重复的酶促步骤组成：脱氢（氧化）、水合、第二次脱氢和碳链的硫解裂解。线粒体FAO缺陷表现为与非酮症低血糖、脂肪肝、肌无力和心肌病相关的严重代谢危象。作为一个群体，线粒体FAO缺陷是最常见的常染色体Recombinant遗传性代谢紊乱之一。治疗干预的主要目的是在代谢应激和禁食期间确保足够的热量摄入，并防止β-氧化中间体的积累。粮农组织在世界各地的几个国家开展了新生儿疾病筛查，增加了早期饮食治疗的机会。关键词：脂肪酸氧化; β-氧化;遗传性代谢缺陷;线粒体
Mitochondrial fatty acid oxidation (FAO) is a major energy-providing pathway under conditions of prolonged fasting, exercise or metabolic stress. A number of inherited disorders affecting this metabolic pathway have been known for almost two decades. Defects of mitochondrial FAO characteristically present with severe metabolic crises associated with low blood glucose (hypoglycaemia) during infancy and childhood and are also a relatively frequent cause of muscle diseases and cardiac muscle disease. The symptoms are typically episodic and often associated with mild viral infections or fasting. Therapeutic interventions are generally effective in preventing metabolic decompensation, which emphasizes the importance of early diagnosis. Diagnostic testing, determining optimal dietary regimens for each disorder and prenatal screening for these disorders may essentially alter an otherwise poor prognosis for many patients with FAO disorders. Key Concepts: Fatty acids can be oxidized by α-oxidation in peroxisomes, by β-oxidation in mitochondria and peroxisomes, and ω-oxidation in the endoplasmic reticulum. Mitochondrial FAO is a major energy-providing pathway under conditions of prolonged fasting, exercise or metabolic stress. A single β-oxidation cycle consists of a series of four repeated enzymatic steps: dehydrogenation (oxidation), hydration, a second dehydrogenation and thiolytic cleavage of the carbon chain. Mitochondrial FAO defects present with severe metabolic crises associated with nonketotic hypoglycaemia, fatty liver, muscle weakness and cardiomyopathy. As a group, mitochondrial FAO defects are among the most common autosomal recessively inherited metabolic disorders. The main objective of therapeutic intervention is to secure sufficient caloric intake during periods of metabolic stress and fasting, and prevent accumulation of β-oxidation intermediates. Neonatal screening of FAO disorders has been initiated in several countries worldwide, improving the opportunities for early dietary therapies. Keywords: fatty acid oxidation; β-oxidation; inherited metabolic defects; mitochondria