This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: arsenate reduction (mycothiol)
|Superclasses:||Detoxification → Arsenate Detoxification|
Some taxa known to possess this pathway include : Corynebacterium glutamicum
Expected Taxonomic Range:
While the jury is still out about whether Napoleon Bonaparte died of arsenic poisoning or cancer [Leslie78, Lewin82], it is agreed by all that arsenic is a potent toxicant. Indeed, the results of exposure to high arsenic concentration in drinking water in West Bengal, India, and Bangladesh are considered by some to be the worst public health disaster in recent history [Aposhian04]. The form of arsenic influences the type and severity of toxicity. Arsenate (AsV) is a structural analog of phosphate, and inhibits phosphorylation processes. For example, ADP-arsenate spontaneously hydrolyzes, resulting in uncoupling of oxidative phosphorylation [Bhuvaneswaran79], while arsenite (AsIII) has a very high affinity for thiol groups, and thus binds to and inhibits many key enzymes that have thiol groups in their active sites. In addition, inorganic arsenic is a potent carcinogen [Vahter02].
Arsenate enters the cell via the phosphate transport systems, such as the Escherichia coli phosphate:H+ symporter PitA and Pst systems. Both prokaryotes and eukaryotes reduce intracellular arsenate to arsenite. However, while prokaryotes can pump arsenite out of the cell by using a dedicated pump (see arsenate detoxification II (glutaredoxin)), multicellular organisms require other means of getting rid of the metal. Certain mammals, including humans, continue by methylating the arsenite to several methylated forms that are excreted from the organism in the urine.
About This Pathway
Many organisms detoxify arsenate using a glutaredoxin-dependent arsenate reductase (see arsenate detoxification I (glutaredoxin)). The bacterium Corynebacterium glutamicum does not possess glutaredoxin, and instead employs mycothiol and mycoredoxin for the purpose of arsenate detoxification [Ordonez09]. It has been shown that mycothiol can reduce arsenate to arsenite on its own. However, the reaction is greatly accelerated in the presence of arsenate reductase proteins and mycoredoxin. The entire process has been reconstituted in vitro and a model has been proposed.
Two arsenate reductase enzymes, encoded by arsC1 and arsC2, catalyze the formation of a mycothiol-arsenate conjugate. A thiolate at the active site of the enzyme activates arsenate, facilitating its transfer to mycothiol. Mycoredoxin reduces the thiol-arseno bond of the conjugate and forms arsenite and a mycothiol-mycoredoxin mixed disulfide. Finally, a second glutathiol molecule releases the mycoredoxin, forming mycothione. The later is restored to mycothiol by the action of mycothione reductase [Ordonez09].
Aposhian04: Aposhian HV, Zakharyan RA, Avram MD, Sampayo-Reyes A, Wollenberg ML (2004). "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 198(3);327-35. PMID: 15276412
Bhuvaneswaran79: Bhuvaneswaran C (1979). "The influence of phosphorylation state ratio on energy conservation in mitochondria treated with inorganic arsenate." Biochem Biophys Res Commun 90(4);1201-6. PMID: 518594
Ordonez09: Ordonez E, Van Belle K, Roos G, De Galan S, Letek M, Gil JA, Wyns L, Mateos LM, Messens J (2009). "Arsenate reductase, mycothiol, and mycoredoxin concert thiol/disulfide exchange." J Biol Chem 284(22);15107-16. PMID: 19286650
Spies94: Spies HS, Steenkamp DJ (1994). "Thiols of intracellular pathogens. Identification of ovothiol A in Leishmania donovani and structural analysis of a novel thiol from Mycobacterium bovis." Eur J Biochem 224(1);203-13. PMID: 8076641
Van12: Van Laer K, Buts L, Foloppe N, Vertommen D, Van Belle K, Wahni K, Roos G, Nilsson L, Mateos LM, Rawat M, van Nuland NA, Messens J (2012). "Mycoredoxin-1 is one of the missing links in the oxidative stress defence mechanism of Mycobacteria." Mol Microbiol 86(4);787-804. PMID: 22970802
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