Arsenic and human species.It is present abundantly in

Arsenic binding to glutathione

 

The metabolism of
Arsenic in the cells involves the reduction of trivalent Arsenic to pentavalent
arsenic. This reaction consists of a redox cycle involving a bio-thiol
(glutathione) with the the production of a tris-glutathionyl-Arsenite
species. The multiple methylations of Arsenite by S-adenosyl-methionine
to the generation of trimethy-arsine (haemolytic toxin) also involves glutathione.
Glutathione presence in the intermediate conjugate forms of methylated Arsenic
species helps these molecules to be removed from the cells by the multidrug
resistance proteins (having ATP-binding cassette). Dimethylarsonic acid
(carcinogenic end-metabolite) also reacts with glutathione having a high
cytolethal effect on cells. Moreover various enzymes and regulatory elements
can contribute to the arsenic biotransformation by contributing individual or
multiple cysteine thiol groups in vicinity in proteins, for example thiol
groups required for catalytic activity.

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Arsenic binding to metallothioneins

Metallothioneins
are expressed by various organisms including bacteria, fungi, planta and
vertebrates. They belong to a protein family of ubiquitous nature characterized
by low molecular weight, high metal and cysteine content. They are capabale of
binding essential metal ions (zinc, copper)_and toxic heavy metals (Arsenic,
cadmium).

Studies have
revealed that bioaccumulation of Arsenic in Sea weed species F. vesiculosus  is achieved through the binding of Arsenite
to the cysteine rich metallothioneins. Moreover arsenic is also known to bind
to mammalian metallothioneins in rabbit and human species.It is present
abundantly in kidneys and liver of mammals. Further studies on human
metallothioneins were consistent with the hypothesis that Arsenite has a
binding preference for three vicinal thiol groups. ? and  ? domain of human metallothionein contains 11
and 9 cysteines respectively. All the 9 cysteine were involved in binding to three
Arsenite molecules in ? domain while in the case of ? domain only 9 out of 11 cysteine
residues were involved in binding to three Arsenites. This leave two cysteine residues
protonated with no fourth Arsenite engaged in binding.