Abstract Fatty acids (FAs) are a highly diverse class of molecules that can have variable chain length, number of double bonds and hydroxylation sites. FAs with 22 or more carbon atoms are described as very long chain fatty acids (VLCFAs). VLCFAs are synthesized in the endoplasmic reticulum (ER) through a four-step elongation cycle by membrane embedded enzymes. VLCFAs are precursors for the synthesis of sphingolipids (SLs) and glycerophospholipids. Besides their role as lipid constituents, VLCFAs are also found as precursors of lipid mediators. Mis-regulation of VLCFA metabolism can result in a variety of inherited diseases ranging from ichthyosis, to myopathies and demyelination. The enzymes for VLCFA biosynthesis are evolutionary conserved and many of the pioneering studies were performed in the model organism Saccharomyces cerevisiae. A growing body of evidence suggests that VLCFA metabolism is intricately regulated to maintain lipid homeostasis. In this review we will describe the metabolism of VLCFAs, how they are synthesized, transported and degraded and how these processes are regulated, focusing on budding yeast. We will review how lipid metabolism and membrane properties are affected by VLCFAs and which impact mutations in the biosynthetic genes have on physiology. We will also briefly describe diseases caused by mis-regulation of VLCFAs in human cells.

中文翻译：

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超长链脂肪酸在酵母生理学和人类疾病中的作用

摘要 脂肪酸 (FAs) 是一类高度多样化的分子，其链长、双键数量和羟基化位点都可变。具有 22 个或更多碳原子的 FA 被描述为超长链脂肪酸 (VLCFA)。VLCFAs 在内质网 (ER) 中通过膜嵌入酶的四步延伸循环合成。VLCFAs 是合成鞘脂 (SL) 和甘油磷脂的前体。除了作为脂质成分的作用外，还发现 VLCFAs 是脂质介质的前体。VLCFA 代谢的错误调节可导致多种遗传性疾病，从鱼鳞病到肌病和脱髓鞘。用于 VLCFA 生物合成的酶在进化上是保守的，许多开创性研究是在模式生物酿酒酵母中进行的。越来越多的证据表明，VLCFA 代谢受到复杂调控以维持脂质稳态。在这篇综述中，我们将描述 VLCFAs 的代谢，它们是如何合成、运输和降解的，以及如何调节这些过程，重点是出芽酵母。我们将回顾 VLCFAs 如何影响脂质代谢和膜特性，以及生物合成基因突变对生理学的影响。我们还将简要描述由人类细胞中 VLCFA 的错误调节引起的疾病。我们将回顾 VLCFAs 如何影响脂质代谢和膜特性，以及生物合成基因突变对生理学的影响。我们还将简要描述由人类细胞中 VLCFA 的错误调节引起的疾病。我们将回顾 VLCFAs 如何影响脂质代谢和膜特性，以及生物合成基因突变对生理学的影响。我们还将简要描述由人类细胞中 VLCFA 的错误调节引起的疾病。