德诺沃肝皮里米丁合成调节系统能量恒温
bioRxiv : the preprint server for biology
|December 3, 2025
概括
禁食血尿素水平与肥胖和2型糖尿病 (T2D) 有关. 抑制肝脏的pyrimidine合成会增加葡萄糖的产生,促进胰岛素抵抗和T2D.
科学领域:
- 代谢性疾病研究研究.
- 肝病学 肝病学是一种肝病学.
- 内分泌学 在内分泌学.
背景情况:
- 禁食血液尿素在肥胖和2型糖尿病 (T2D) 中升高.
- 肝脏尿素生物合成在这些条件中的作用尚不清楚.
- 饮食引起的肥胖和禁食会降低肝脏的pyrimidine合成.
研究的目的:
- 研究肝脏尿素生物合成在肥胖和T2D中的重要性.
- 阐明肝皮里米丁合成抑制影响新陈代谢平衡的机制.
- 探索尿素,金胺合成和肝脏中的葡萄糖代谢之间的相互作用.
主要方法:
- 研究了禁食和饮食诱导的肥胖对肝 pyrimidine 合成的影响.
- 评估了抑制皮里米丁合成对肝脏葡萄糖生产和胰岛素清除的影响.
- 研究了循环尿素在调节肝细胞和脂肪细胞中胺合成中的作用.
- 研究了尿素和抑制的金胺合成对葡萄糖生成的协同作用.
主要成果:
- 抑制肝皮里米丁合成促进肥胖和胰岛素抵抗.
- 降低皮里米丁合成导致肝脏葡萄糖产量增加和胰岛素清除率降低,独立于血尿素水平.
- 在禁食度下,尿素在肝细胞中优先抑制比脂肪细胞中的金胺合成.
- 禁食时的尿素水平加剧葡萄糖生成,当皮里米丁合成被抑制时,突出了协同效应.
结论:
- 肝皮里米丁合成抑制是肥胖和T2D的代谢功能障碍的一个关键因素.
- 尿素扮演着双重的角色:抑制皮里米丁合成,并在特定条件下促进葡萄糖生成.
- 尿液代谢和肝皮里米丁合成中的乱为代谢性疾病的病因提供了新的视角.
相关概念视频
Biosynthesis of Nucleic Acids
924
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...
924
Amino Acid Biosynthetic Pathways
998
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...
998
Regulation of Metabolism
11.4K
Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...
11.4K
Other Glycolytic Pathways
784
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...
784
Introduction to Metabolism
2.5K
Metabolism encompasses all biochemical reactions in a living organism, facilitating both the breakdown and synthesis of biomolecules. These metabolic processes are categorized into catabolic and anabolic pathways, which operate in a coordinated manner to ensure energy balance and cellular function.Catabolic Pathways and Energy ReleaseCatabolic pathways involve the breakdown of complex macromolecules such as carbohydrates, lipids, and proteins into smaller structures like monosaccharides, fatty...
2.5K
Allosteric Proteins-ATCase
6.4K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
6.4K


