Regulation of HMG-CoA reductase

描述（申请人提供）：3-羟基-3-甲基戊二酰辅酶A还原酶（HMGR）是一种存在于几乎所有生物体内的重要酶，其结构在原核生物和真核生物之间表现出显著的保守性，表明具有共同的进化遗产。在人类中，HMGR在过去二十年中受到了极大的关注，因为它是胆固醇合成的限速步骤，并且通过药物（如他汀类药物）控制它具有重大的健康益处。然而，尽管如此，在其监管方面仍有一些重大问题需要解决。在本次研究申请中提出的研究中，我将研究HMGR在龙虾下颌骨器官中的调控作用。龙虾和其他节肢动物一样，不合成胆固醇。由于少了一条使用HMGR产物的途径，这种酶的调节可能不那么复杂。此外，HMGR活性在这个组织中非常高，因为下颌骨器官产生大量的倍半萜，甲基法脂酸酯。最后，HMGR活性似乎可能受神经内分泌肽的调节。这些研究可能对这种酶的功能和调控产生独特的见解。

DESCRIPTION (provided by applicant): 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is an important enzyme found in nearly all living organisms, Its structure shows remarkable conservation between prokaryotes and eukaryotes, indicating a common evolutionary heritage. In humans, HMGR has received enormous attention in the past two decades because it is the rate-limiting step in the synthesis of cholesterol and its control by drugs (e.g., statins) has had major health benefits. However, in spite of this attention there are still major issues that need to be resolved regarding its regulation. In the studies proposed in this research application, I will study the regulation of HMGR in the mandibular organ of the lobster. Lobsters, like all other arthropods, do not synthesize cholesterol. With one less pathway using the product of HMGR, the regulation of this enzyme is likely to be less complicated. In addition, HMGR activity is very high in this tissue, since the mandibular organ produces large quantities of a sesquiterpene, methyl farnesoate. Finally, it seems likely that HMGR activity is regulated by neuroendocrine peptides. These studies may yield unique insights into the function and regulation of this enzyme.