对超氧化物脱酶的活性结合机制和对环境中普遍存在的酸盐及其水解产物的毒理影响:将体外生物试验与分子动力学模拟相结合
Xiuli Fan1, Chenggang Gu1, Zhengyuan Gao1
1State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008, PR China; University of the Chinese Academy of Sciences, Beijing 100049, PR China.
International journal of biological macromolecules
|April 30, 2025
概括
酸 (PAE) 和它们的代谢物,特别是单酸 (MAE) 和酸 (PA),显著抑制了超氧化物溶解酶 (SOD) 的活性. 酸盐对抗氧化酶的这种破坏有助于氧化应激和代谢综合征的风险.
科学领域:
- 环境毒理学环境毒理学
- 生物化学 生物化学
- 分子生物学分子生物学
背景情况:
- 酸 (PAE) 是常见的塑化剂,具有已知的环境风险.
- PAE与氧化应激和代谢综合征有关,但它们对抗氧化酶如超氧化物转化酶 (SOD) 的影响尚不清楚.
研究的目的:
- 研究PAE及其代谢物如何影响SOD活动的分子机制.
- 为了确定SOD中酸盐诱导的特定相互作用和结构变化.
主要方法:
- 利用生物测试和理论模拟来研究PAE,代谢物 (MAE,PA) 和SOD之间的相互作用.
- 分析了SOD活性,酶结构和结合亲缘关系的变化.
主要成果:
- 酸代谢物 (MAE和PA) 强烈抑制了SOD活性,较短的侧链更有效.
- PAE对SOD活动的影响最小.
- 抑制是由于MAEs/PA与SOD残留的紧密结合,导致结构不稳定和功能受损.
- 在Arg141.1.上观察到SOD抑制和结合能之间的相关性.
结论:
- 甲酸代谢物,而不是PAE本身,是SOD活动的主要破坏者.
- 在SOD中的结构变化,特别是Arg141的结构变化,是甲酸盐诱导的氧化应激的关键.
- 141和相关残留物可以作为生物标志物,用于早期检测酸盐诱导的氧化应激.
相关概念视频
Toxic Reactions: Overview
894
When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
894
Types of Toxins
1.3K
Humans continually engage with an environment rich in potentially harmful chemicals. These are introduced to our bodies through inhalation, ingestion, or skin contact. These chemicals exist in various forms, such as air and environmental pollutants, agricultural chemicals, organic solvents, and heavy metals.
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
1.3K
Mutagenicity and Carcinogenicity
1.1K
Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
1.1K


