Arsenic biotransformation

In the Challenger mechanism or scheme, oxidative methylation of arsenicals containing As(III) produces a methylated product that contains As(V). Because methylation is oxidative, As(V) must be reduced to trivalency before it can be methylated. Hence, the pathway for the formation of mono-, di-, and trimethylated arsenic species consists of alternating oxidation and reduction reactions (Chapter 2). 

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The marine facultative anaerobe bacterium Serratia marinoruhm and the yeast Rhodotoruhi rubra both methylate arsenate ion to methylarsonate, but only the latter produces cacodylic acid (258). Human volunteers who ingested 500 fig doses of As as sodium arsenite, sodium methylarsonate, and sodium cacodylate excreted these compounds in their urine (259). Of these three, approximately 75% of the sodium arsenite is methylated, while 13% of methylarsonate is methylated. Rat liver subcellular fractions methylated sodium arsenate in vitro, providing the first direct evidence for possible mammalian methylation independent of symbiotic bacteria (260). Shariatpanahi el al. have reported kinetics studies on arsenic biotransformation by five species of bacteria (261). They found that the As(V)-As(IIl) reduction followed a pattern of two parallel first-order reactions, while the methylation reactions all followed first-order kinetics. Of the five species tested, only the Pseudomonas produced all four metabolites (arsenite, methylarsonate, cacodylate, trimethylarsine) (261). 

Zakharyan, R.A. and Aposhian, H.V. (1999) Enzymatic reduction of arsenic compounds in mammalian systems the rate-limiting enzyme of rabbit liver arsenic biotransformation is MMA(V) reductase. Chemical Research in Toxicology, 12(12), 1278-83. 

A Geiszinger, W Goessler, SN Pedersen, KA Francesconi. Arsenic biotransformation by the brown macroalga Fucus serratus. Environ Toxicol Chem, in press. 

Castiehouse, H. Smith, C. Raab, A. Deacon, C. Meharg, A. A. Feidmann, J. Biotransformation and Accumulation of Arsenic in Soii Amended with Seaweed. Environ. Sci. Technol. 2003, 37, 951-957. 

Melarsoprol is a divalent arsenical. It reacts with sulfhydryl groups. Melarsoprol is used for the late stage of sleeping sickness. It has to be administered intravenously. Slow i.v. injection is recommended. It is widely distributed and enters the CNS. It has a very short elimination half-life as it is biotransformed to a pentavalent arsenical. Adverse effects include hypersensitivity reactions and gastrointestinal toxicity causing severe vomiting and abdominal pain. CNS reactions are most serious as the encephalopathy may be fatal. Hemolytic anemia may... 

Dimercaprol is FDA-approved as single-agent treatment of acute poisoning by arsenic and inorganic mercury and for the treatment of severe lead poisoning when used in conjunction with edetate calcium disodium (EDTA see below). Although studies of its metabolism in humans are limited, intramuscularly administered dimercaprol appears to be readily absorbed, metabolized, and excreted by the kidney within 4-8 hours. Animal models indicate that it may also undergo biliary excretion, but the role of this excretory route in humans and other details of its biotransformation are uncertain. 

C. Marine Animals Toxicological Considerations Biotransformation of Marine Arsenic Compounds... 

The impacts of arsenic on human health are left to the next chapter, which includes discussions on the toxic effects of arsenic and its biotransformations. Chapter 5 reviews the history of arsenic utilization in human societies, examples of unintentional poisoning events, the role of arsenic in crime, and recent production and market trends. While the discussions in Chapter 3 often have widespread applications in a variety of natural environments, Chapter 6 cites specific field cases, where human activities and natural occurrences of arsenic in water, soils, and sediments have produced exceptionally serious threats to local environments and human populations. 

Francesconi, K.A. and Edmonds, J.S. (1994) Biotransformation of arsenic in the marine environment, in Arsenic in the Environment Parti Cycling and Characterization, (ed. J.O. Nriagu), John Wiley Sons, Ltd, New York, pp. 221-61. 

Vahter, M. (1981) Biotransformation of trivalent and pentavalent inorganic arsenic in mice and rats. Environmental Research, 25(2), 286-93. 

Cullen et al. (1994) have proposed a possible mechanism of arsenic methylation after the study in which arsenite, arsenate, monomethyl-arsonate or dimethylarsinic acid were added to the growth medium in the presence of the unicellular alga Polyphsa peniculus. Evidence of arsenic biomethylation by the micro-organism Apiotrichum humicola in the presence of L-methionine-methyl-d3 has come from the same laboratory (Cullen et al., 1995). Their findings point to the role of S-adenosylmethionine, or a related sulfonium compound as possible methyl donors. Arsenic biomethylation and biotransformation has also been demonstrated in a freshwater environment (Kuroiwa et al., 1994). 

Kuroiwa, T., Ohki, A., Naka, K. and Maeda, S. (1994) Biomethylation and biotransformation of arsenic in a freshwater food chain green alga (Chlorella vulgaris) — shrimp (Neocaridina denticulata) — Killifish (Oryzias latipes). Appl. Organomet. Chem., 8, 325-333. 

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