Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Arsenate Detoxification
Homo sapiens
Metabolic Pathway
Arsenate is a compound similar to phosphate, but containing an arsenic atom instead of the phosphorous. As such, it is treated similarly to a phosphate ion. However, if the arsenate replaces inorganic phosphates in glycolysis, it allows glycolysis to proceed, but does not generate ATP, uncoupling glycolysis. It can also bind to lipoic acid in the Krebs cycle, leading to a greater loss of ATP.
Arsenate can enter into the cell via aquaporins 7 and 9, as well as facilitated glucose transporter members 1 and 4 of solute carrier family 2, and does so by diffusion.
Once inside the cell, the arsenate can be converted to arsenite via the glutathione S-transferase omega-1 enzyme, or it can be converted to ribose-1-arsenate via the purine nucleoside phosphorylase. Ribose-1-arsenate then can spontaneously form arsenite through a reaction involving hydrogen and dihydrolipoate. After arsenite has been formed by either of these methods, arsenite methyltransferase catalyzes its formation into methylarsonate. From here, it forms methylarsonite via the glutathione S-transferase omega-1 enzyme again. The methylarsonite reacts with S-adenosylmethionine, catalyzed by arsenite methyltransferase, in order to become dimethylarsinate. Finally, the compound once again interacts with the glutathione S-transferase omega-1 enzyme to form dimethylarsinous acid, the final compound in this pathway.
References
Arsenate Detoxification References
Vahter M: Mechanisms of arsenic biotransformation. Toxicology. 2002 Dec 27;181-182:211-7.
Pubmed: 12505313
Lin S, Shi Q, Nix FB, Styblo M, Beck MA, Herbin-Davis KM, Hall LL, Simeonsson JB, Thomas DJ: A novel S-adenosyl-L-methionine:arsenic(III) methyltransferase from rat liver cytosol. J Biol Chem. 2002 Mar 29;277(13):10795-803. doi: 10.1074/jbc.M110246200. Epub 2002 Jan 14.
Pubmed: 11790780
Li J, Waters SB, Drobna Z, Devesa V, Styblo M, Thomas DJ: Arsenic (+3 oxidation state) methyltransferase and the inorganic arsenic methylation phenotype. Toxicol Appl Pharmacol. 2005 Apr 15;204(2):164-9. doi: 10.1016/j.taap.2004.12.002.
Pubmed: 15808521
Aposhian HV: Enzymatic methylation of arsenic species and other new approaches to arsenic toxicity. Annu Rev Pharmacol Toxicol. 1997;37:397-419. doi: 10.1146/annurev.pharmtox.37.1.397.
Pubmed: 9131259
Aposhian HV, Zakharyan RA, Avram MD, Sampayo-Reyes A, Wollenberg ML: A review of the enzymology of arsenic metabolism and a new potential role of hydrogen peroxide in the detoxication of the trivalent arsenic species. Toxicol Appl Pharmacol. 2004 Aug 1;198(3):327-35. doi: 10.1016/j.taap.2003.10.027.
Pubmed: 15276412
Rosen BP, Liu Z: Transport pathways for arsenic and selenium: a minireview. Environ Int. 2009 Apr;35(3):512-5. doi: 10.1016/j.envint.2008.07.023. Epub 2008 Sep 11.
Pubmed: 18789529
Lewin PK, Hancock RG, Voynovich P: Napoleon Bonaparte--no evidence of chronic arsenic poisoning. Nature. 1982 Oct 14;299(5884):627-8.
Pubmed: 6750413
Leslie AC, Smith H: Napoleon Bonaparte's exposure to arsenic during 1816. Arch Toxicol. 1978 Dec 11;41(2):163-7.
Pubmed: 367316
Healy SM, Wildfang E, Zakharyan RA, Aposhian HV: Diversity of inorganic arsenite biotransformation. Biol Trace Elem Res. 1999 Jun;68(3):249-66. doi: 10.1007/BF02783907.
Pubmed: 10328340
Bhuvaneswaran C: The influence of phosphorylation state ratio on energy conservation in mitochondria treated with inorganic arsenate. Biochem Biophys Res Commun. 1979 Oct 29;90(4):1201-6.
Pubmed: 518594
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Downloads
Settings