探索对2-Oxoglutarate依赖的二氧化原酶的酸盐要求
Carlos C Smith-Díaz1, Andrew B Das1, Tomasz P Jurkowski2
1Ma̅tai Ha̅ora - Centre for Redox Biology and Medicine, Department of Biomedical Science and Pathology, University of Otago, Christchurch, Christchurch 8140, New Zealand.
Journal of medicinal chemistry
|January 30, 2025
概括
双氧酸盐依赖的二氧化基酶 (2-OGDD) 需要l-酸 (维生素C) 才能达到最佳功能. 阿斯科伯酸盐通过清除激素和管理金属离子来支持酶活性.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 细胞的新陈代谢
背景情况:
- 依赖2氧格酸盐的二氧化基酶 (2-OGDDs) 是人类催化化反应的关键酶.
- 这些酶参与各种细胞过程,包括新陈代谢,DNA/RNA脱甲基化和原蛋白形成.
- 催化机制涉及一种高度氧化的ferryl-oxo物种,它们依赖非血红素铁和分子氧气.
研究的目的:
- 探索l-亚斯科布酸 (亚斯科布酸盐,维生素C) 在支持2-OGDD酶活性方面的特定和基本作用.
- 提出一个全面的理论,说明酸盐的可用性如何影响2-OGDD的功能.
- 与其他降解剂相比,研究阿斯科尔酸盐独特的刺激作用背后的机制.
主要方法:
- 对各种2-OGDD的研究结果的审查和综合.
- 分析与酶机制有关的酸盐的化学特性.
- 检查在酶活性部位内对阿斯酸盐立体特异性结合的证据.
主要成果:
- 亚酸盐作为一种有效的基因清除剂,对酶功能至关重要.
- 亚斯科伯酸盐表现出降解和结合过渡金属的倾向,有助于催化.
- 有证据表明,在酶活性部位中,酸具有立体特异性的结合,这解释了它的特定作用.
结论:
- 酸的可用性对2-氧格酸依赖的二氧化基酶的活性至关重要.
- 亚斯科伯酸盐作为激素清除剂和金属化剂的双重功能是其特定酶支持的关键.
- 了解 Askorbate 的作用,可以了解酶调节和潜在的治疗策略.
更多相关视频
相关概念视频
Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation
135
Glutathione, a tripeptide made up of glutamate, cysteine, and glycine, is a critical player in the detoxification of drugs and xenobiotics via a process known as glutathione conjugation or mercapturic acid formation. This phase II biotransformation reaction involves the covalent binding of glutathione to a drug or its metabolite, enhancing the compound's water solubility and enabling its excretion.
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
135
Pyruvate Oxidation
158.2K
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+...
158.2K
Phase I Oxidative Reactions: Overview
227
Phase I biotransformation, or functionalization, is a crucial chemical process that converts drugs and other xenobiotics into more water-soluble forms, facilitating expulsion from the body. It involves oxidative, reductive, and hydrolytic reactions that add or unveil polar functional groups on lipophilic substrates. Key players in phase I reactions are the mixed-function oxidases. Situated in liver cell microsomes, these enzymes predominantly carry out drug metabolism. They require molecular...
227
Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide
9.8K
Alkenes are converted to 1,2-diols or glycols through a process called dihydroxylation. It involves the addition of two hydroxyl groups across the double bond with two different stereochemical approaches, namely anti and syn. Dihydroxylation using osmium tetroxide progresses with syn stereochemistry.
9.8K
Oxidative Cleavage of Alkenes: Ozonolysis
9.9K
In ozonolysis, ozone is used to cleave a carbon–carbon double bond to form aldehydes and ketones, or carboxylic acids, depending on the work-up.
Ozone is a symmetrical bent molecule stabilized by a resonance structure.
Ozone is a symmetrical bent molecule stabilized by a resonance structure.
9.9K
Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids
5.6K
Diols are compounds with two hydroxyl groups. In addition to syn dihydroxylation, diols can also be synthesized through the process of anti dihydroxylation. The process involves treating an alkene with a peroxycarboxylic acid to form an epoxide. Epoxides are highly strained three-membered rings with oxygen and two carbons occupying the corners of an equilateral triangle. This step is followed by ring-opening of the epoxide in the presence of an aqueous acid to give a trans diol.
5.6K


