重定向中间代谢以抵消化物中毒
Vik S Bebarta1,2, Anjali K Nath3,4,5
1Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
概括
化物中毒破坏细胞代谢,将能量生产从氧化酸化转移到糖解. 新的研究探索重定向中间代谢,以开发针对这些代谢途径的新型化物抗毒.
科学领域:
- 生物化学 生物化学
- 毒理学 毒理学 毒理学
- 代谢学 代谢学 代谢学
背景情况:
- 化物是一种具有历史意义的毒素,具有复杂的细胞毒性机制.
- 以前试图开发基于代谢物的化物抗剂的尝试都没有成功.
- 最近在代谢学和药物向方面的进展为化物抗剂开发提供了新的方法.
研究的目的:
- 审查化物毒性机制,重点关注中间代谢.
- 确定对化物中毒代谢理解的知识差距.
- 探索针对化物中毒的基于新陈代谢的治疗策略.
主要方法:
- 审查关于化物毒性和代谢的现有文献.
- 分析基于质谱的新陈代谢学的最新进展.
- 讨论细胞下药物向和基因组编辑应用.
主要成果:
- 化物将细胞代谢从氧化酸化转移到糖解.
- 代谢组为治疗干预提供了众多途径.
- 准中间代谢是一种与当前治疗方法相比的范式转变.
结论:
- 重定向中间代谢是一种有前途的策略,用于化物抗药的开发.
- 基于新陈代谢的抗药可以解决化物引起的广泛细胞损伤.
- 对代谢位的进一步研究可能会改善化物中毒的长期结果.
相关概念视频
Phase II Reactions: Miscellaneous Conjugation Reactions
48
Phase II biotransformations are detoxification mechanisms that conjugate xenobiotics with endogenous substances, neutralizing their toxicity.
A key example involves the conjugation of cyanide ions, which impair cellular respiration and alter hemoglobin into non-oxygen-carrying cyanmethemoglobin. To neutralize this threat, a sulfur atom from thiosulphate is transferred to the cyanide ion, catalyzed by the enzyme rhodanese, resulting in an inactive compound called thiocyanate. The production of...
A key example involves the conjugation of cyanide ions, which impair cellular respiration and alter hemoglobin into non-oxygen-carrying cyanmethemoglobin. To neutralize this threat, a sulfur atom from thiosulphate is transferred to the cyanide ion, catalyzed by the enzyme rhodanese, resulting in an inactive compound called thiocyanate. The production of...
48
Antidotes
619
Antidotes are medicinal substances used to counteract the harmful effects of toxins or drugs in the body. They function in various ways, each uniquely designed to combat specific toxic compounds.
Specific antidotes operate by inhibiting the enzymes that control biochemical pathways, reducing the production of harmful metabolites.
An example of an antidote is atropine, which counteracts the detrimental effects of cholinesterase inhibitors. It achieves this by deactivating muscarinic receptors,...
Specific antidotes operate by inhibiting the enzymes that control biochemical pathways, reducing the production of harmful metabolites.
An example of an antidote is atropine, which counteracts the detrimental effects of cholinesterase inhibitors. It achieves this by deactivating muscarinic receptors,...
619
Enhanced Elimination of Poison
486
Poison can be effectively removed from the gastrointestinal (GI) tract through various decontamination procedures.
Antidotes serve a crucial role in counteracting the effects of poison by inhibiting enzymes responsible for producing harmful drug metabolites. In some cases, these toxic metabolites can be neutralized by endogenous cosubstrates, which are maintained at specific concentrations to prevent interaction with cellular macromolecules and subsequent cell death.
Renal excretion is the...
Antidotes serve a crucial role in counteracting the effects of poison by inhibiting enzymes responsible for producing harmful drug metabolites. In some cases, these toxic metabolites can be neutralized by endogenous cosubstrates, which are maintained at specific concentrations to prevent interaction with cellular macromolecules and subsequent cell death.
Renal excretion is the...
486
The Electron Transport Chain
16.3K
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
16.3K
Prevention of Further Absorption of Poison
797
In cases of acute poisoning, the primary objective is to prevent further absorption of the toxic substance into the body. Immediate interventions using various decontamination techniques targeting the gastrointestinal (GI) tract can achieve this. Decontamination is crucial to prevent poison from entering the systemic circulation, which involves washing affected areas with water and mild soap and removing contaminated clothing. Once external decontamination is done, attention must be turned to...
797
Anticholinesterase Agents: Poisoning and Treatment
813
Anticholinesterases, also known as cholinesterase inhibitors, work by blocking the breakdown of acetylcholine, leading to its accumulation in the synaptic cleft. This accumulation indirectly enhances both muscarinic and nicotinic actions. These agents are classified as reversible or irreversible based on their mechanism of action.
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...
813


