Effect of Phospholipids on the Function of Membrane Bound Enzymes

磷脂对膜结合酶功能的影响

• 批准号: 9005299
• 负责人: David Zakim
• 金额: $ 19万
• 依托单位: Joan and Sanford I. Weill Medical College of Cornell University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 1992-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9005299&HistoricalAwards=false
• 关键词: Effect; Phospholipids; Function; Membrane; Bound

It has been shown previously that the functional state of UDP-glucuronosyltransferase (GT) is determined in part by the lipid environment. Evidence obtained in the last grant period suggests that GT is an oligomer regulated by protein- protein interactions, which are modulated in turn by the lipids at the annulus. Moreover, it appears that the organization of protein-protein interactions as well as the distribution of lipids in untreated microsomes, which constrain the maximal activity of GT, is not the thermodynamically most stable state of microsomes. This metastable organization and associated constraint on the activity of microsomal enzymes seem to be general properties of microsomal enzymes in that two other enzymes studied behave like GT. This study establishes the validity of the above ideas via detailed studies of GT, glucose-6-Pase, and acylCoA ligase in microsomes and in pure, reconstituted systems. If current studies establish that pure GT is an oligomer the conditions under which it dissociates will be determined to establish the factors that account for constaint and organization in intact microsomes. Independent of these results ongoing studies are being conducted on the influence of the lipid environment on the functional state and stability of GT. This research is fundamental to our understanding of the organization and function of membrane proteins as well as the role of lipids in modulating the behavior of these proteins. Progress in this area will have an impact on basic cellular biology, biochemistry and pathobiology.***//

先前已经表明， UDP-葡萄糖醛酸基转移酶（GT）部分地由 脂质环境 在上次赠款中获得的证据 这表明GT是一种由蛋白质调节的寡聚体， 蛋白质相互作用，这反过来又被调节， 纤维环处的脂质。 此外，看来， 蛋白质相互作用的组织以及 脂质在未处理微粒体中的分布， 限制GT的最大活性，不是 微粒体的代谢最稳定状态。 这 亚稳态组织和相关的约束 微粒体酶的活性似乎是一般性质 在其他两种酶中， 行为像GT。这项研究建立了有效性的 通过对GT，葡萄糖-6-磷酸， 微粒体和纯复溶样品中的酰基CoA连接酶 系统. 如果目前的研究确定纯GT是一种 低聚物的条件下，它离解将是 决心确定导致 在完整的微粒体中保持和组织。 独立 目前正在对这些结果进行研究， 脂质环境对功能状态的影响 GT的稳定性。 这项研究对于我们理解 膜蛋白的组织和功能以及 脂质在调节这些蛋白质的行为中的作用。 这一领域的进展将对基础蜂窝网络产生影响。 生物学、生物化学和病理生物学 *//