赫索胺途径代谢物增强蛋白质质量控制并延长寿命
Martin S Denzel1, Nadia J Storm1, Aljona Gutschmidt2
1Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, Cologne 50931, Germany.
Cell
|March 18, 2014
概括
在六胺通路中促进N-甘氨酸前体的合成,改善了内 плазма网膜 (ER) 蛋白质的稳定性,并延长了寿命. 补充N-乙葡萄糖胺可以减缓衰老,并有利于C. elegans的神经毒性疾病模型.
科学领域:
- 生物化学 生物化学
- 老年学是指老年学的学科.
- 分子生物学分子生物学
背景情况:
- 衰老的特点是蛋白质平衡的下降,导致与年龄相关的疾病.
- 细胞内膜网膜 (ER) 对于蛋白质的合成和成熟至关重要,需要N-结合的糖化来进行适当的折叠.
- 功能失调的蛋白质稳态和ER压力是衰老和神经退行性疾病的标志.
研究的目的:
- 调查N-甘氨酸前体合成在HEXOSAMIN通路中对ER蛋白质稳态和寿命的作用.
- 确定是否提高N-甘氨酸前体的可用性可以减轻与年龄相关的衰退和疾病病理.
- 阐明涉及寿命延长的潜在机制,包括蛋白质降解途径.
主要方法:
- 利用模型生物C. elegans研究衰老和蛋白质平衡.
- 用N-乙葡萄糖胺 (GlcNAc) 补充生长介质,以增加N-甘油素前体水平.
- 评估寿命,蛋白质聚合,与ER相关的蛋白质降解 (ERAD),蛋白质体活性和自.
- 检查了不同的神经毒性疾病模型来评估治疗潜力.
主要成果:
- 通过赫索胺途径增加N-甘氨酸前体的合成改善了ER蛋白质的稳态.
- 用N-乙葡萄糖胺补充剂显著减缓了野生类型C. elegans的衰老和延长寿命.
- 在神经毒性疾病模型中,N-乙葡萄糖胺治疗减轻了病理.
- 延长寿命和减少蛋白质聚合与增强的ER相关蛋白质降解,蛋白质体活性和自有关.
结论:
- 激活六胺通路和N-乙葡萄糖胺补充剂可以增强细胞蛋白质质量控制机制.
- 这些干预措施改善了ER蛋白的平衡,并通过加强蛋白质降解途径来延长寿命.
- 准赫索胺通路和N-甘氨酸合成是一种潜在的治疗策略,用于与年龄相关的和蛋白质毒性疾病.
相关概念视频
The Proteasome
1.6K
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
1.6K
The Proteasome
7.8K
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
7.8K
Amino Acid Biosynthetic Pathways
1.8K
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...
1.8K
Drug Metabolism: Phase II Reactions
4.7K
Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
4.7K
Phase II Reactions: Sulfation and Conjugation with α-Amino Acids
1.4K
Sulfation and α-amino acid conjugation are two critical biotransformation reactions in drug metabolism. Sulfation, a phase II biotransformation reaction, involves adding a polar sulfate group to a drug, enhancing its water solubility and promoting excretion. This process can either co-occur with or occur independently of glucuronidation. Nonmicrosomal sulfotransferase enzymes catalyze the process. The reaction involves 3'-phosphoadenosine-5'-phosphosulfate or PAPS coenzyme...
1.4K
Biosynthesis of Nucleic Acids
1.7K
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...
1.7K


