pyruvate脱酶复合体的调节:在癌症中跳不同鼓的舞蹈
Mulchand S Patel1, Todd C Rideout2
1Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, New York, USA.
International journal of cancer
|October 4, 2025
概括
癌细胞通过大量的翻译后修改和转录控制来重新编程pyruvate脱酶复合体 (PDC) 调节. 这些癌症特异性机制为癌症中的代谢重编程提供了新的治疗点.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 癌症新陈代谢 癌症新陈代谢
背景情况:
- 在正常细胞中,通过酸化,酸盐脱酶复合体 (PDC) 的活性受到严格的调节.
- 癌细胞表现出改变的代谢途径,包括PDC调节的显著修改.
研究的目的:
- 综合审查癌细胞中PDC的多种调节机制.
- 突出新的癌症特异性PDC调节途径及其影响.
主要方法:
- 对癌症中PDC调节的现有文献的审查.
- 对影响PDC的各种翻译后修改 (PTM) 的分析.
- 检查转录和新型调节途径.
主要成果:
- 在癌症中PDC调节涉及超过12个PTM,包括乙化,乳化和甲基化,除了酸化.
- 转录调节PDC激酶/酸酶和AMPK介导的酸化有助于活性PDC.
- 通过PDC转移到细胞核,便于组织素乙化,绕过线粒体的乙-CoA供应限制.
结论:
- 癌细胞使用广泛和新的机制来调节PDC活动和新陈代谢.
- 了解这些特定于癌症的PDC法规对于开发向癌症疗法至关重要.
相关概念视频
Electron Transport Chain: Complex I and II
18.3K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
18.3K
Adaptive Mechanisms in Cancer Cells
6.8K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.8K
mTOR Signaling and Cancer Progression
4.6K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
4.6K
Pyruvate Oxidation
168.1K
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+...
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+...
168.1K
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
Epigenetic Regulation
3.7K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.7K


