磷脂酰乙醇胺
生物
生物化学
磷脂酰丝氨酸
乙醇胺
酶
生物合成
基因表达
磷脂
基因
分子生物学
磷脂酰胆碱
膜
作者
Morgan D. Fullerton,Fatima Hakimuddin,Marica Bakovic
摘要
The CDP-ethanolamine pathway is responsible for the de novo biosynthesis of ethanolamine phospholipids, where CDP-ethanolamine is coupled with diacylglycerols to form phosphatidylethanolamine. We have disrupted the mouse gene encoding CTP:phosphoethanolamine cytidylyltransferase, Pcyt2, the main regulatory enzyme in this pathway.Intercrossings of Pcyt2 ؉/؊ animals resulted in small litter sizes and unexpected Mendelian frequencies, with no null mice genotyped.The Pcyt2 ؊/؊ embryos die after implantation, prior to embryonic day 8.5.Examination of mRNA expression, protein content, and enzyme activity in Pcyt2 ؉/؊ animals revealed the anticipated 50% decrease due to the gene dosage effect but rather a 20 to 35% decrease.[ 14 C]ethanolamine radiolabeling of hepatocytes, liver, heart, and brain corroborated Pcyt2 gene expression and activity data and showed a decreased rate of phosphatidylethanolamine biosynthesis in heterozygotes.Total phospholipid content was maintained in Pcyt2 ؉/؊ tissues; however, this was not due to compensatory increases in the decarboxylation of phosphatidylserine.These results establish the necessity of Pcyt2 for murine development and demonstrate that a single Pcyt2 allele in heterozygotes can maintain phospholipid homeostasis.
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