Hi Nguyen, you ask a very interesting question. I know a little about this and I can say that the arsenic methylation is a complex problem. The metabolic sequence yields several distinct products, each with its own unique toxicology. Arsenite is the first of these products - followed by various arsenic methylated compounds. It was traditionally thought that the arsenic methylation process was a detoxification process - but given that the methylated products are more toxic than arsenate, it is now considered (among many authors) a bioactivation pathway. Biotransformation of inorganic arsenicals occurs mainly in the liver and approximately 70% of the metabolites are readily excreted in the urine. Simply put - arsenite is the first product of the biotransformation process. I hope this helps. Best wishes with your research.

To decrease the deleterious effect, the transformation of As species occurs to mobile As from one tissue to another. The transformation and its mechanisms have been well documented in various plant species including rice, tomato, and Pteris vittata. After reduction, As(III) is detoxified through a complex formation with thiol-rich peptides  or glutathione (GSH) leading to low efflux or long-distance transport to other tissues.

In a word, As(III) is easy  translocation in plant which can avoid accumulation of As(V) in the root. The high toxicity will not occur in the root leading to plant death.

The reduction of As (V) to As (III) occurs both enzymatically and non-enzymatically. In the non-enzymatic pathway, two molecules of glutathione (GSH) are able to reduce As (V) to As (III). Enzymatically, As (V) is directly reduced to As-III by arsenate reductase (ACR). This reduction process is considered one of the important steps as detoxification pathways of arsenic found in plants.

Hello Nguyen, I think it depends a lot on the animal/plant you are considering. Arsenic metabolism can vary a lot among different phyla. Personally, I conducted some research on bioaccumulation, bioconcentration and biotransformation of arsenicals in Hediste diversicolor and noticed that as a "defensive" strategy, there is in the animal's tissue the production of DIMETHYL ARSENATE (you can take a look at my papers if you want). But (just to give you an idea of how different the metabolism can be), Regoli et al. demonstrated that Sabellidae are able to convert less toxic molecules to Arsenate as antipredatory defence. 

Hope it helps,

All the best,

Andrea

In many animal cells As5+ is reduced to As3+, which increases toxicity. But As3+ is then methylated to form monomethylarsonic acid (MMAV), which is reduced, methylated etc to form MMAIII, DMAV and DMAIII. The methylation process is detoxifying, whereas the reduction is toxifying. I believe organic arsenic is more easily excreted by the kidneys, and so at the cost of making a few very toxic trivalent arsenic species along the way it is better in the long run (it seems) that it is made organic to get rid of it quicker.

I briefly describe this process in my review "Arsenic, reactive oxygen, and endothelial dysfunction" published in JPET this year. 

There is also another good review: Vahter 2002 Mechanisms of arsenic biotransformation (can't remember which journal)

Rachel Martin - what you said about arsenic methylation being bioactivation process is true in the sense that MMAIII and DMAIII have a number of different cellular targets to AsIII. The only reason methylation is not, on the whole, considered a detoxification process is because the organic pentavalent species go on to form toxic products. But methylation itself (which also makes arsenic pentavalent) does actually detoxify the trivalent species that preceded it. 

I just wanted to add this latter answer for clarity, because it may seem that mine and Rachel's answer contradict each other, but they dont

Hi all, I have a slightly different evolutionary look on prokaryotes that might help in answering your question. 

Rachel's conclusion is correct, arsenite is the first step in a long detoxification pathway. Bacteria have been exposed to arsenic long before gaseous oxygen has been present on this planet. Consequently, bacteria have evolved a complex arsenic detoxification pathway for the reduced form of arsenic (As(III)). When oxygen was later present in our atmosphere, bacteria were then also exposed to the oxidized form of arsenic (As(V)). 

As you have pointed out, both of these species have completely different toxicities and mode of toxic actions (i.e. As(V)=phosphate mimic whereas As(III)=ROS). Rather than evolving a completely novel pathway, it was simpler to reduce As(V) to As(III) by evolving a small arsenate reductase enzyme (arsC). Even though ArsC acts as a catalyses to form a more toxic compound, the reduction of As(V) to As(III) allowed bacteria to use their traditional pathway to transport and detoxify As(III) from their cytoplasm.

This conclusion might not apply directly to eukaryotes, but I think it can help in answering your question regarding the order of detoxification.