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

甲基乙二醛（MG）是一种高度反应性的代谢产物，可与蛋白质形成加合物，导致蛋白质功能障碍。在之前的资助期间，我们发现MG水平升高会通过一种新的未知机制导致关键代谢酶丙酮酸脱氢酶（PDH）的活性降低。MG水平在糖尿病患者中升高。此外，已知糖尿病患者具有降低的PDH活性，尽管其机制尚未完全理解。我们的目标是联合收割机这些观察，了解机制如何MG调节PDH的活动，以及是否发生在糖尿病患者。

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.