Zeng Zhenhua, Huang Qiaobing, Mao Liangfeng, Wu Jie, An Sheng, Chen Zhongqing, Zhang Weijin
Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Pathophysiology, Guangdong Provincial Key Lab of Shock and Microcirculation, Southern Medical University, Guangzhou, China.
Front Nutr. 2021 Dec 14;8:783164. doi: 10.3389/fnut.2021.783164. eCollection 2021.
Anaerobic glycolysis is the process by which glucose is broken down into pyruvate and lactate and is the primary metabolic pathway in sepsis. The pyruvate dehydrogenase complex (PDHC) is a multienzyme complex that serves as a critical hub in energy metabolism. Under aerobic conditions, pyruvate translocates to mitochondria, where it is oxidized into acetyl-CoA through the activation of PDHC, thereby accelerating aerobic oxidation. Both phosphorylation and acetylation affect PDHC activity and, consequently, the regulation of energy metabolism. The mechanisms underlying the protective effects of PDHC in sepsis involve the regulation on the balance of lactate, the release of inflammatory mediators, the remodeling of tricarboxylic acid (TCA) cycle, as well as on the improvement of lipid and energy metabolism. Therapeutic drugs that target PDHC activation for sepsis treatment include dichloroacetate, thiamine, amrinone, TNF-binding protein, and ciprofloxacin. In this review, we summarize the recent findings regarding the metabolic regulation of PDHC in sepsis and the therapies targeting PDHC for the treatment of this condition.
无氧糖酵解是葡萄糖分解为丙酮酸和乳酸的过程，是脓毒症的主要代谢途径。丙酮酸脱氢酶复合体（PDHC）是一种多酶复合体，是能量代谢的关键枢纽。在有氧条件下，丙酮酸转运至线粒体，通过激活PDHC被氧化为乙酰辅酶A，从而加速有氧氧化。磷酸化和乙酰化均影响PDHC活性，进而影响能量代谢的调节。PDHC在脓毒症中的保护作用机制涉及对乳酸平衡、炎症介质释放、三羧酸（TCA）循环重塑以及脂质和能量代谢改善的调节。针对PDHC激活用于脓毒症治疗的药物包括二氯乙酸、硫胺素、氨力农、肿瘤坏死因子结合蛋白和环丙沙星。在本综述中，我们总结了关于脓毒症中PDHC代谢调节以及针对PDHC治疗该病症的最新研究发现。
