A lecithin cholesterol acyltransferase-like gene mediates diacylglycerol esterification in yeast
A lecithin cholesterol acyltransferase-like gene mediates diacylglycerol esterification in yeast
复制标题
DOI：
10.1074/jbc.c000144200
复制
发表时间：
2000-05-26
影响因子：
4.8
通讯作者：
Sturley, SL
中科院分区：
文献类型：
--
作者：
Oelkers, P;Tinkelenberg, A;Sturley, SL
甘油三酸酯生物合成的最后一步是甘油二酯的酯化。为了研究这种反应在模式真核生物，酿酒酵母，我们调查了五个候选基因的序列保守哺乳动物酰基转移酶。这些基因中的四个与最近鉴定的酰基辅酶A二酰基甘油酰基转移酶相似，并且当删除时，通过掺入放射性标记的油酸酯或甘油来测量，导致甘油三酯合成很少或没有减少。相比之下，LRO1，人类卵磷脂胆固醇酰基转移酶的同源物的删除，导致在甘油三酯的合成显着减少，而LRO1的过度表达产生了显着增加甘油三酯的生产。在体外微粒体测定确定，Lro1介导的酯化二酰基甘油使用磷脂酰胆碱作为酰基供体。残留的甘油三酯的生物合成，持续在LRO 1缺失株主要是酰基辅酶A依赖性和介导的基因，结构上不同于以前确定的哺乳动物二酰基甘油酰基转移酶。这些机制也可能存在于哺乳动物细胞中。
The terminal step in triglyceride biosynthesis is the esterification of diacylglycerol. To study this reaction in the model eukaryote, Saccharomyces cerevisiae, we investigated five candidate genes with sequence conservation to mammalian acyltransferases. Four of these genes are similar to the recently identified acyl-CoA diacylglycerol acyltransferase and, when deleted, resulted in little or no decrease in triglyceride synthesis as measured by incorporation of radiolabeled oleate or glycerol. By contrast, deletion of LRO1, a homolog of human lecithin cholesterol acyltransferase, resulted in a dramatic reduction in triglyceride synthesis, whereas overexpression of LRO1 yielded a significant increase in triglyceride production. In vitro microsomal assays determined that Lro1 mediated the esterification of diacylglycerol using phosphatidylcholine as the acyl donor. The residual triglyceride biosynthesis that persists in the LRO1 deletion strain is mainly acyl-CoA-dependent and mediated by a gene that is structurally distinct from the previously identified mammalian diacylglycerol acyltransferase. These mechanisms may also exist in mammalian cells.