Sepsis is a heterogeneous syndrome resulting from a dysregulated host response to infection. It is considered as a global major health priority. Sepsis is characterized by significant metabolic perturbations, leading to increased circulating metabolites such as lactate. In mammals, pyruvate is the primary substrate for lactate production. It plays a critical role in metabolism by linking glycolysis, where it is produced, with the mitochondrial oxidative phosphorylation pathway, where it is oxidized. Here, we provide an overview of all cytosolic and mitochondrial enzymes involved in pyruvate metabolism and how their activities are disrupted in sepsis. Based on the available data, we also discuss potential therapeutic strategies targeting these pyruvate-related enzymes leading to enhanced survival.

中文翻译：

---

脓毒症诱导的丙酮酸代谢变化：见解和可能的治疗方法。


脓毒症是一种异质性综合征，由宿主对感染的反应失调引起。它被认为是全球主要的卫生重点。脓毒症的特征是显著的代谢扰动，导致循环代谢物（如乳酸）增加。在哺乳动物中，丙酮酸是乳酸产生的主要底物。它通过将产生糖酵解的糖酵解与线粒体氧化磷酸化途径（被氧化）联系起来，在新陈代谢中发挥关键作用。在这里，我们概述了所有参与丙酮酸代谢的胞质酶和线粒体酶，以及它们在脓毒症中的活性是如何被破坏的。根据现有数据，我们还讨论了针对这些丙酮酸相关酶的潜在治疗策略，从而提高生存率。