在组织和瘤中采用de novo和salvage纯素合成途径
Diem H Tran1, Dohun Kim1, Rushendhiran Kesavan1
1Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Cell
|June 1, 2024
概括
细胞使用de novo和救援途径来产生核酸. 这项研究揭示了循环中的腺素和素有效地提供纯素,并且抑制纯素回收会减缓瘤的生长.
科学领域:
- 生物化学
- 分子生物学
- 癌症新陈代谢
背景情况:
- 精氨酸核酸对于DNA/RNA合成,信号传递和能量是必不可少的.
- 细胞使用de novo和救援途径进行 purin合成.
- 增殖细胞被认为主要使用de novo合成,而差异化组织则有利于挽救.
研究的目的:
- 调查循环 purin 前体的体内作用.
- 为了比较 de novo 和救援途径在瘤中的贡献.
- 确定纯素代谢对瘤生长的影响.
主要方法:
- 在小鼠中的定量代谢分析.
- 精氨酸前体 (腺素,素,低素) 的使用.
- 抑制精氨酸救援途径.
主要成果:
- 氨酸和氨酸是有效的循环氨酸来源; 低氨酸很难恢复.
- 这两种途径都有助于瘤蛋白池的形成.
- 补充核酸可以加速瘤的生长.
- 抑制氨酸的储存会减缓瘤的进展.
结论:
- 循环中的纯素前体在体内有不同的利用.
- 在瘤新陈代谢中发挥关键作用.
- 针对纯素的救援是癌症的潜在治疗策略.
更多相关视频
14:22Free Radicals in Chemical Biology: from Chemical Behavior to Biomarker Development
Published on: April 15, 2013
20.2K
10:38Simultaneous Quantification of Selected Kynurenines Analyzed by Liquid Chromatography-Mass Spectrometry in Medium Collected from Cancer Cell Cultures
Published on: May 9, 2020
3.4K
相关概念视频
Nucleotide Excision Repair
3.5K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.5K
Drug Metabolism: Phase II Reactions
3.8K
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...
3.8K
Interactions Between Signaling Pathways
6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
Treatment Resistant Cancers
3.3K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K
Long-patch Base Excision Repair
7.0K
Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
7.0K
Base Excision Repair
22.3K
One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
The first step of...
22.3K
