线粒体的酸盐代谢和谷氨酸溶解切换平稳状态和紧急骨髓形成
Hannah A Pizzato1,2, Yahui Wang3, Michael J Wolfgang4,5
1Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA.
The Journal of experimental medicine
|May 30, 2023
概括
线粒体的酸盐代谢对于稳定状态的骨髓形成至关重要. 然而,在紧急血液形成过程中,原始细胞转换为谷氨酸溶解,以快速恢复髓状细胞.
科学领域:
- 血液学 血液学 血液学
- 细胞代谢 细胞代谢
- 免疫学 免疫学 免疫学
背景情况:
- 血液形成,血细胞形成的过程,依赖于特定的代谢途径.
- 了解这些代谢需求是解决造血性疾病的关键.
研究的目的:
- 调查长链脂肪酸氧化,谷氨酸溶解和线粒体pyruvate进口在血液形成中的作用.
- 在稳定状态和压力条件下定义不同血统的代谢依赖.
主要方法:
- 在小鼠中,Cpt2,Gls或Mpc2的条件基因切除.
- 血液细胞系和造血干细胞和祖细胞的分析.
- 竞争性骨髓模拟物和稳定同位素追踪.
主要成果:
- 切除Cpt2或Gls对大多数血系的影响很小.
- Mpc2 缺乏严重减少成熟的髓状细胞和T细胞,但髓状细胞的祖先通过依赖谷氨酸分解的增殖突发恢复.
- 在MPc2损失或循环胺治疗后,氨酸溶解 (Gls) 对于骨髓回收至关重要.
结论:
- 线粒体酸盐进口 (Mpc2) 对于在正常条件下维持骨髓形成至关重要.
- 在应对压力时,氨酸溶解对紧急骨髓形成和骨髓回收至关重要.
相关概念视频
Fates of Pyruvate
8.7K
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...
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...
8.7K
Other Glycolytic Pathways
53
The pentose phosphate pathway (PPP) operates in parallel with glycolysis, facilitating the metabolism of both pentoses and glucose. This pathway consists of two distinct phases: the oxidative and non-oxidative phases. While it does not directly generate ATP, the intermediates formed during the process can integrate into glycolysis, contributing to cellular energy metabolism when required.Oxidative Phase: NADPH ProductionThe oxidative phase of the pentose phosphate pathway is primarily...
53
What is Glycolysis?
166.1K
Overview
Cells make energy by breaking down macromolecules. Cellular respiration is the biochemical process that converts "food energy" (from the chemical bonds of macromolecules) into chemical energy in the form of adenosine triphosphate (ATP). The first step of this tightly regulated and intricate process is glycolysis. The word glycolysis originates from the Latin glyco (sugar) and lysis (breakdown). Glycolysis serves two main intracellular functions: generating ATP and generating...
Cells make energy by breaking down macromolecules. Cellular respiration is the biochemical process that converts "food energy" (from the chemical bonds of macromolecules) into chemical energy in the form of adenosine triphosphate (ATP). The first step of this tightly regulated and intricate process is glycolysis. The word glycolysis originates from the Latin glyco (sugar) and lysis (breakdown). Glycolysis serves two main intracellular functions: generating ATP and generating...
166.1K
Biosynthesis of Nucleic Acids
88
Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
88
Amino Acid Biosynthetic Pathways
46
Amino acid biosynthesis is essential for cell growth, protein synthesis, and metabolic regulation. Cells generate essential and non-essential amino acids from metabolic intermediates to sustain vital biological functions. These intermediates originate from key metabolic pathways: glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway. Important precursors include α-ketoglutarate, pyruvate, oxaloacetate, phosphoenolpyruvate, and erythrose-4-phosphate, which...
46
Glycolysis
68
Glycolysis, the Embden-Meyerhof pathway, is a central metabolic pathway involved in glucose catabolism. It is highly conserved across most organisms, reflecting its fundamental role in cellular energy production. This process occurs in the cytoplasm and can function both in the presence and absence of oxygen, making it versatile for various organisms and environmental conditions.Stages of GlycolysisGlycolysis is a ten-step pathway that converts glucose into pyruvate, generating a net gain of...
68


