Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innrain, Innsbruck, Austria.
Biochimie. 2013 Jan;95(1):59-65. doi: 10.1016/j.biochi.2012.06.027. Epub 2012 Jul 4.
Ether lipids are an emerging class of lipids which have so far not been investigated and understood in every detail. They have important roles as membrane components of e.g. lens, brain and testis, and as mediators such as platelet-activating factor. The metabolic enzymes for biosynthesis and degradation have been investigated to some extent. As most involved enzymes are integral membrane proteins they are tricky to handle in biochemical protocols. The sequence of some ether lipid metabolising enzymes has only recently been reported and other sequences still remain obscure. Defined enzymes without assigned sequence are known as orphan enzymes. One of these enzymes with uncharacterised sequence is plasmanylethanolamine desaturase, a key enzyme for the biosynthesis of one of the most abundant phospholipids in our body, the plasmalogens. This review aims to briefly summarise known functions of ether lipids, give an overview on their metabolism including the most prominent members, platelet-activating factor and the plasmalogens. A special focus is set on the description of orphan enzymes in ether lipid metabolism and on the successful strategies how four previous orphans have recently been assigned a sequence. Only one of these four was characterised by classical protein purification and sequencing, whereas the other three required alternative strategies such as bioinformatic candidate gene selection and recombinant expression or development of an inhibitor and multidimensional metabolic profiling.
醚脂是一类新兴的脂质，迄今为止尚未被全面研究和了解。它们作为晶状体、大脑和睾丸等细胞膜成分，以及血小板激活因子等介质，具有重要作用。它们的生物合成和降解代谢酶已在一定程度上得到研究。由于大多数相关酶都是整合膜蛋白，因此在生化方案中处理起来具有一定难度。一些醚脂代谢酶的序列最近才被报道，而其他序列仍然不清楚。没有指定序列的定义酶被称为孤儿酶。其中一种具有未鉴定序列的酶是溶血磷脂酰乙醇胺去饱和酶，这是我们体内最丰富的磷脂之一——脑磷脂生物合成的关键酶。本文旨在简要总结醚脂的已知功能，概述其代谢途径，包括最突出的成员——血小板激活因子和脑磷脂。本文特别关注醚脂代谢中孤儿酶的描述，以及最近如何通过四种先前的孤儿酶序列分配策略。其中只有一种通过经典的蛋白质纯化和测序进行了表征，而其他三种则需要替代策略，如生物信息学候选基因选择和重组表达，或开发抑制剂和多维代谢分析。
