Navigating flux control through a branched metabolic pathway

该项目旨在发现甲羟戊酸途径的控制点和程序，甲羟戊酸途径是产生胆固醇和类异戊二烯的一种重要的细胞代谢途径。对其调控的知识在很大程度上仅限于一种酶(HMGCR)。该项目将确定对后期类固醇生产环节的调控如何影响甲氧戊酸途径的早期异戊二烯-片段；调查胆固醇合成的两条替代途径是如何运作和被调控的；以及探索一个协调的、可能是合作的转录计划。该项目有望为细胞如何控制这些关键脂质提供有价值的知识，最终将为治疗胆固醇过剩和这一途径中的缺陷的疾病提供更好的方法。

This project aims to uncover control points and programmes in the mevalonate pathway, an important cellular metabolic pathway that produces cholesterol and isoprenoids. Knowledge of its regulation is largely restricted to just one enzyme (HMGCR). This project will determine how regulation of the later sterol-producing segment affects the early isoprenoid-segment of the mevalonate pathway; investigate how the two alternate routes to cholesterol synthesis operate and are regulated; and explore a co-ordinated and possibly co-operative transcriptional program. This project is expected to provide valuable knowledge of how cells control these critical lipids, which will ultimately inform better ways to treat diseases of cholesterol excess and defects in this pathway.