Regulation of PDH activity by MG and the impact on diabetes complications (A03)

甲基乙二醛(MG)是一种高活性的代谢物，在蛋白质上形成加合物，导致蛋白质功能障碍。在之前的资助期间，我们发现MG水平升高导致关键代谢酶丙酮酸脱氢酶(PDH)活性降低，其机制尚不清楚。糖尿病患者体内镁含量升高。此外，众所周知，糖尿病患者的PDH活性降低，尽管其机制尚不完全清楚。我们的目标是结合这些观察，从机制上了解MG是如何调节PDH活性的，以及这是否发生在糖尿病患者身上。

Methylglyoxal (MG) is a highly reactive metabolite that forms adducts on proteins, leading to protein dysfunction. In the previous funding period, we found that elevated MG levels lead to reduced activity of a key metabolic enzyme, Pyruvate Dehydrogenase (PDH), via a novel unknown mechanism. MG levels are elevated in diabetic patients. Furthermore, diabetic patients are known to have reduced PDH activity, although the mechanism is not completely understood. We aim to combine these observations, to understand mechanistically how MG regulates PDH activity, and whether this is happening in diabetic patients.