Arsenic Sketchy | Toxicology forensic science | Forensic medicine lecture | Forensic Medicine

The metabolism of arsenic has a direct impact on its toxic effects, although the exact mechanism of action is not fully understood, there are several hypotheses. Arsenate (pentavalent) and arsenite (trivalent) are the most common toxic inorganic forms; each has a different proposed mechanism based on valence state.

Arsenate (pentavalent arsenic) may replace phosphate in several reactions. Arsenate has a similar structure and similar properties to phosphate. In vitro studies show arsenate reacts with glucose to form glucose-6-arsenate, which resembles glucose-6-phosphate. Glucose-6-arsenate is a substrate for glucose-6-phosphate dehydrogenase and can inhibit hexokinase, which plays an essential role in glycolysis; a series of reactions that extract energy from glucose in both anaerobic and aerobic pathways. ATP gets generated in the presence of phosphate; however, in the presence of arsenate, depletion of ATP has been observed secondary to diminished ATP formation.

Arsenite (trivalent arsenic) is considered to be the more toxic inorganic form compared to arsenate (pentavalent arsenic). Arsenite reacts with thiol and sulfhydryl groups, which are major organic components to multiple proteins and enzymes found throughout the body. These reactions cause dysregulation and inhibition of proteins and enzymes involved. One crucial enzyme effected is pyruvate dehydrogenase, which is a protein complex that requires lipoic acid, a dithiol, for activation. Pyruvate dehydrogenase (PDH) is a vital enzyme in the citric acid cycle; an altercation of PDH can lead to impairment of cellular respiration and ATP formation. Arsenite can reversibly bind to sulfhydryl groups which are believed to cause dilation and increased permeability of capillaries. Arsenite's affinity for thiols, more predominately, dithiols leads to favorable transfer of arsenite to the chelating agent, dithiol 2,3-dimercaptosuccinic also known succimer.
Definitive mechanism of action for the carcinogenic effects of arsenic remain unverified. Proposed mechanisms include alteration of DNA repair, DNA methylated oxidative stress and genotoxicity
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