When absorbed in human body As(III) is the major species reacting with the SULFHYDRIL (SH) group enzymes blocking their activity in turn physiological symptoms appears on the body.

thanks Supriya

As (III) is water soluble and is methylated in liver, then to be rapidly excreted. So,  it's  As(V) that  is deposits mainly in  karatinous tissues in the body.

THANX TAPAN, but yours and Supriya's reply is opposite. kindly help which one is accurate.

Dear Dr. Sudhir,

Thanks for your comment. For low dose or short exposure, It seems right.

Arsenic clearance requires reduction and methylation. Reduction requires glutathione (GSH) and methylation requires SAME coenzyme.

For short exposure, AsIII will be rapidly excreted. For high dose or long exposure, it is complecated: exessive reduction & methylation of Arsenic may not proceed as usual due to depletion in GSH and methyl group, that hampers DNA methylation, In such case, there remains the possibility of both the species to be the body, with As III as the dominant one (not sure).  I am sorry for your time. 

Pl. see the link

www.atsdr.cdc.gov/csem/csem.asp?csem=1&po=9

Dr. Sudhir Srivastava,  ·

1. As Tapan ponted out, arsenic metabolism from the blood involves reduction and methylation. Methylated forms of both As(III) and As(V) are generated during metabolism. The relative preponderance of a these forms depends on inter individual enzyme variations and enzymic methylation efficiency.

2. The metabolism of inorganic arsenic involves two metabolic events, reduction and oxidative methylation. Recent studies have highlighted methylation caused re-elicitation of toxic responses; methylated metabolites, in particular the trivalent forms, appear to evoke greater toxicity than the inorganic arsenicals do.

3. Pentavalent arsenate undergoes reduction in blood, and is predominantly taken up in liver, and is metabolized by reduction and oxidative methylation. Methylated metabolites, along with inorganic arsenicals, are associated with urinary excretion. The enzyme, arsenic (oxidation state, +3) methyltransferase (AS3M), methylates  arsenite ([As(III)]and generates  [MMA(V)], which subsequently gets reduced to [MMA(III)]; further, second methylation and reduction steps occur to produce dimethyl derivatives, [DMA(V)] and [DMA(III)], respectively. MMA(III) has been documented to be the most toxic of all arsenic metabolites with a propensity to induce malignant transformation of cells in vitro. Individual variations (and enzyme polymorphism) in the methylation mediating enzyme, AS3M, can influence the efficiency of arsenic methylation.  

4. Current studies aimed at evaluating the association between urinary profiles of arsenic and human diseases predominantly determine inorganic arsenate and arsenite and the two organic forms of methylated metabolites, namely  the pentavalent form of monomethylarsonic acid [MMA(V)], formed by the first methylation of  arsenite [As (III)], and dimethylarsinic acid [DMA(V)], generated during the second methylation nd reduction steps (see paragraph #3 above) . These two organic forms of arsenic,  MMA(V) and DMA(V), are deemed to be of toxicological consequence. Reviews of current findings suggest a decrease in methylation capacity with increased [MMA(V)] percentage and diminished  [DMA(V)] percentage.  

5. The renewal of interest in the potential use of arsenicals as chemotherapeutic agents has led to some resurgence in exploring the biochemistry of As(III) species. 

Chithan has very well summarized the sequence of arsenic biostransformation in the body. The process of AsV reduction to AsIII in the blood is quite rapid, and so AsIII is the major inorganic species. 

In my review from this year there is a Figure summarizing this sequence of events:

Ellinsworth DC (2015) Arsenic, reactive oxygen, and endothelial dysfunction. J Pharmacol Exp Ther