Frédéric M. Vaz, Sacha Ferdinandusse, Gajja S. Salomons, Ronald J. A. Wanders
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引用次数: 0
摘要
人类从外源性膳食来源和/或内源性乙酰-CoA合成中获取脂肪酸(FA),但有些脂肪酸仅来自外源性来源("必需脂肪酸")。一旦进入细胞,脂肪酸可能会发生各种不同的修饰,包括活化为相应的 CoA 酯、引入双键、2-羟基化和ω-羟基化以及链延长,从而产生一个细胞脂肪酸池,可用于合成更复杂的脂类。复合脂质的生物特性在很大程度上取决于其分子组成,即掺入这些脂质种类的脂肪酸。这立即解释了为什么人类存在一系列遗传疾病,这些疾病往往因负责这些脂肪酸修饰的酶的编码基因之一发生变异而导致严重的临床后果。本综述旨在描述有关脂肪酸平衡和相关遗传疾病的知识现状。这包括脂肪酸活化、脱饱和、2-羟基化和ω-羟基化及链延长的紊乱,也包括脂肪酸分解的紊乱,包括过氧物酶体和线粒体α-和β-氧化的紊乱。
Humans derive fatty acids (FA) from exogenous dietary sources and/or endogenous synthesis from acetyl‐CoA, although some FA are solely derived from exogenous sources (“essential FA”). Once inside cells, FA may undergo a wide variety of different modifications, which include their activation to their corresponding CoA ester, the introduction of double bonds, the 2‐ and ω‐hydroxylation and chain elongation, thereby generating a cellular FA pool which can be used for the synthesis of more complex lipids. The biological properties of complex lipids are very much determined by their molecular composition in terms of the FA incorporated into these lipid species. This immediately explains the existence of a range of genetic diseases in man, often with severe clinical consequences caused by variants in one of the many genes coding for enzymes responsible for these FA modifications. It is the purpose of this review to describe the current state of knowledge about FA homeostasis and the genetic diseases involved. This includes the disorders of FA activation, desaturation, 2‐ and ω‐hydroxylation, and chain elongation, but also the disorders of FA breakdown, including disorders of peroxisomal and mitochondrial α‐ and β‐oxidation.
期刊介绍:
The Journal of Inherited Metabolic Disease (JIMD) is the official journal of the Society for the Study of Inborn Errors of Metabolism (SSIEM). By enhancing communication between workers in the field throughout the world, the JIMD aims to improve the management and understanding of inherited metabolic disorders. It publishes results of original research and new or important observations pertaining to any aspect of inherited metabolic disease in humans and higher animals. This includes clinical (medical, dental and veterinary), biochemical, genetic (including cytogenetic, molecular and population genetic), experimental (including cell biological), methodological, theoretical, epidemiological, ethical and counselling aspects. The JIMD also reviews important new developments or controversial issues relating to metabolic disorders and publishes reviews and short reports arising from the Society''s annual symposia. A distinction is made between peer-reviewed scientific material that is selected because of its significance for other professionals in the field and non-peer- reviewed material that aims to be important, controversial, interesting or entertaining (“Extras”).