相关实验视频

Updated: Sep 14, 2025

Author Spotlight: Advanced Integrated Model for Sepsis-Induced Myopathy and Single-Cell Metabolic Analysis

Author Spotlight: Advanced Integrated Model for Sepsis-Induced Myopathy and Single-Cell Metabolic Analysis

Published on: June 14, 2024

解釋 mitochondrial pyruvate 功能障礙以減輕高乳酸血症和毒性致死性

Louise Nuyttens¹, Marah Heyerick¹, Geike Heremans²

¹Center for Inflammation Research, Vlaams Instituut voor Biotechnologie (VIB), Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.

|July 22, 2025

概括

败血症会导致高乳糖血症,原因是酸盐脱酶综合体 (PDC) 功能失调,由胺酸盐 (TPP) 短缺引起. 补充TPP恢复了pyruvate代谢,防止败血症,并使得安全的葡萄糖管理.

科学领域:

生物化学生物化学
病理生理学病理生理学
线粒体的新陈代谢

背景情况:

败血症是一种危及生命的疾病,与乳酸水平升高 (超乳酸血症) 相关,这是死亡率的一个关键预测因素.
超乳酸血症使得血症患者的葡萄糖管理复杂化.
导致败血症高乳酸血症的确切机制尚不完全理解.

研究的目的:

在败血症期间调查肝脏线粒体的代谢变化.
阐明酸盐脱酶复合体 (PDC) 在败血症引起的高乳糖血症中的作用.
为了确定治疗策略,针对毒症中的线粒体功能障碍.

主要方法:

利用结和刺穿 (CLP) 鼠标模型来诱导多微生物败血症.
分析了肝脏线粒体中的pyruvate处理途径.
评估了酸盐脱酶复合体 (PDC) 的活性和辅因子状态.

主要成果:

由pyruvate驱动的线粒体呼吸在败血症小鼠中显著受损.
确定PDC功能障碍,而不是酸盐的吸收或氧化,是呼吸障碍的主要原因.
败血性线粒体表现出减少的胺酸盐 (TPP) 辅因子水平,导致PDC功能障碍.
补充TPP恢复了pyruvate氧化,并改善了败血症小鼠的存活率.
在败血症的背景下,TPP使得安全有效的葡萄糖管理成为可能.

结论:

败血症诱导的高乳糖血症主要是由胺酸盐 (TPP) 缺乏引起的,导致酸盐脱酶复合体 (PDC) 功能障碍.
补充TPP是一种潜在的治疗策略,可以恢复线粒体功能并改善败血症的结果.
结合TPP和葡萄糖疗法为治疗败血症相关的代谢障碍提供了一个有希望的方法.

关键词:

CP:新陈代谢过程中的新陈代谢.CP: 微生物学微生物学乳酸乳酸是一种乳酸.线粒体中的线粒体.皮鲁酸是一种酸盐.这是一种血症.胺胺的使用方法

更多相关视频

Hyperpolarized 13C Metabolic Magnetic Resonance Spectroscopy and Imaging

Hyperpolarized 13C Metabolic Magnetic Resonance Spectroscopy and Imaging

Published on: December 30, 2016

The Lactate Dehydrogenase Sequestration Assay — A Simple and Reliable Method to Determine Bulk Autophagic Sequestration Activity in Mammalian Cells

The Lactate Dehydrogenase Sequestration Assay — A Simple and Reliable Method to Determine Bulk Autophagic Sequestration Activity in Mammalian Cells

Published on: July 27, 2018

相关概念视频

Fates of Pyruvate

Fates of Pyruvate

Pyruvate is the end product of glycolysis, where glucose is oxidized to pyruvate, simultaneously reducing NAD+ to NADH. Two molecules of ATP are also produced by substrate-level phosphorylation.
In aerobic organisms, pyruvate is metabolized via the citric acid cycle to produce reduced coenzymes NADH and FADH2. These coenzymes are then oxidized in the electron transport chain to produce ATP and, in the process, regenerate the NAD+ and FAD. As seen in some cell types and organisms, fermentation...

Inborn Errors of Metabolism

Inborn Errors of Metabolism

Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...

Pyruvate Oxidation

Pyruvate Oxidation

After glycolysis, the charged pyruvate molecules enter the mitochondria via active transport and undergo three enzymatic reactions. These reactions ensure that pyruvate can enter the next metabolic pathway so that energy stored in the pyruvate molecules can be harnessed by the cells.
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...

Muscle Recovery and Fatigue

Muscle Recovery and Fatigue

Muscle fatigue refers to the decline in a muscle's ability to maintain the force of contraction after prolonged activity. It primarily stems from changes within muscle fibers. Even before experiencing muscle fatigue, one may feel tired and have the urge to stop the activity. This response, known as central fatigue, occurs due to changes in the central nervous system, namely the brain and spinal cord. While there is no single mechanism that induces fatigue, it may serve as a protective...

Microbial Fermentation

Microbial Fermentation

Fermentation is a crucial anaerobic metabolic process that enables microbes to derive energy from sugar without relying on oxygen or an electron transport chain. This process is fundamental to various biological and industrial applications and is classified based on the metabolic products generated.Role of Pyruvate in FermentationPyruvate and its derivatives serve as key electron acceptors in fermentative pathways. The oxidation of NADH to regenerate NAD+ is essential for the continuation of...