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Amino Acid Biosynthetic Pathways01:29

Amino Acid Biosynthetic Pathways

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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...
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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...
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Translocation of Proteins into the Mitochondria01:19

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Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
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Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
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Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
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Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
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线粒体的NADP (H) 生成对蛋白生物合成至关重要

Jiajun Zhu1, Simon Schwörer1, Mirela Berisa2

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Science (New York, N.Y.)
|April 23, 2021
PubMed
概括

线粒体NAD激酶2 (NADK2) 产生了对蛋白生物合成和原蛋白生产至关重要的NADP. 没有它会阻碍细胞生长,

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科学领域:

  • 生物化学
  • 细胞生物学
  • 代谢调节

背景情况:

  • 尼古丁胺氨基二核酸盐 (NADP+) 和其减少形式 (NADPH) 是减少代谢的关键辅酶.
  • 线粒体NADP(H) 稳态对于细胞功能至关重要,NAD酶2 (NADK2) 被确定为关键生产者.

研究的目的:

  • 在细胞代谢和增殖中研究由NADK2产生的线粒体NADP (H) 的特定作用.
  • 阐明NADK2缺乏对关键代谢途径和细胞功能的影响.

主要方法:

  • 使用NADK2删除的人类细胞系.
  • 评估了线粒体叶酸和三酸循环活动.
  • 监测细胞增殖,氧化应激,蛋白生物合成和原蛋白的产生.

主要成果:

  • 在最小的介质中,NADK2删除损害了细胞增殖,这种缺陷通过补充物得到了挽救.
  • 通过NADK2产生的线粒体NADP (H) 对于减少谷氨酸和随后的蛋白生物合成至关重要.
  • 线粒体中的NADP (H) 可用性会影响介质细胞中的原蛋白合成.

结论:

  • 线粒体的NADK2-依赖的NADP (H) 生产对蛋白生物合成至关重要,支持细胞蛋白合成.
  • 线粒体的NADP (H) 池在介质细胞的原蛋白生产中起着重要作用.
  • 通过对线粒体NADP的控制,NADK2是细胞生长和生物合成过程的关键调节者.