Arsenic biochemistry
[2] The evidence that arsenic may be a beneficial nutrient at trace levels below the background to which living organisms are normally exposed has been reviewed.
For example, the mold Scopulariopsis brevicaulis produces significant amounts of trimethylarsine if inorganic arsenic is present.
[6] The organic compound arsenobetaine is found in some marine foods such as fish and algae, and also in mushrooms in larger concentrations.
In clean environments, the edible mushroom species Cyanoboletus pulverulentus hyperaccumulates arsenic in concentrations reaching even 1,300 mg/kg in dry weight; cacodylic acid is the major As compound.
[10] Trimethylarsine, once known as Gosio's gas, is an intensely malodorous organoarsenic compound that is commonly produced by microbial action on inorganic arsenic substrates.
Although phosphate and arsenate are structurally similar, there is no evidence that arsenic replaces phosphorus in DNA or RNA.
Man-made sources of arsenic, include wastes from mineral processing, swine and poultry farms.
[16] For example, many ores, especially sulfide minerals, are contaminated with arsenic, which is released in roasting (burning in air).
In such processing, arsenide is converted to arsenic trioxide, which is volatile at high temperatures and is released into the atmosphere.
Despite, or possibly because of, its long-known toxicity, arsenic-containing potions and drugs have a history in medicine and quackery that continues into the 21st century.
The related drug Melarsoprol is still in use against late-state African trypanosomiasis (sleeping sickness), despite its high toxicity and possibly fatal side effects.
Inorganic arsenic and its compounds, upon entering the food chain, are progressively metabolised (detoxified) through a process of methylation.
[33] With the uptake of arsenic within cells and the subsequent reactions that result in the production of reactive oxygen species (ROS), the Nrf2 unbinds and becomes active.
[39] Arsenic is a cause of mortality throughout the world; associated problems include heart, respiratory, gastrointestinal, liver, nervous and kidney diseases.
This threat led to many studies on antidotes and an expanded knowledge of the interaction of arsenic compounds with living organisms.
By contrast, arsenic oxide is an approved and effective chemotherapeutic drug for the treatment of acute promyelocytic leukemia (APL).
[3] Due to its similar structure and properties, pentavalent arsenic metabolites are capable of replacing the phosphate group of many metabolic pathways.
[40] Unlike the importance of phosphate in glycolysis, the presence of arsenate restricts the generation of ATP by forming an unstable anhydride product, through the reaction with D-glyceraldehyde-3-phosphate.
[40] The anhydride 1-arsenato-3-phospho-D-glycerate generated readily hydrolyzes due to the longer bond length of As-O compared to P-O.
[40] Arsenite (III) metabolites, on the other hand, have limited effect on ATP production in red blood cells.
[40] Enzymes and receptors that contain thiol or sulfhydryl functional groups are actively targeted by arsenite (III) metabolites.
[28] The reactive oxygen species are capable of stressing the endoplasmic reticulum, which increases the amount of the unfolded protein response signals.
[28] Another mechanism in which reactive oxygen species cause cell death would be through the cytoskeleton rearrangement, which affects the contractile proteins.
[28] Mitochondrial damage is known to cause the release of reactive nitrogen species, due to the reaction between superoxides and nitric oxide (NO).
[28] Nitric oxide (NO) is a part of cell regulation, including cellular metabolism, growth, division and death.
[28] In cases of chronic arsenic exposure, the nitric oxide levels are depleted, due to the superoxide reactions.
[43][44] A series of experimental observations suggest that the arsenic genotoxicity is primarily linked to the generation of reactive oxygen species (ROS) during its biotransformation.
[64] The excess amount of granulocytes and monocytes lead to a chronic state of inflammation, which might result in cancer development.
Once bound to the chelating agent the molecules can be excreted, and therefore free inorganic arsenic atoms are removed from the body.
Other chelating agents can be used, but may cause more side effects than British Anti-Lewisite (BAL, Dimercaprol), succimer (DMSA) and (DMPS).
