Inorganic arsenic has been recognized as the most potent human carcinogen. In the body, during the process of arsenic metabolism, inorganic arsenic is methylated to monomethylarsenous acid and finally to dimethylarsinic acid, followed by excretion through urine. Thus, arsenic exposure may cause DNA hypomethylation due to continuous methyl depletion, facilitating aberrant gene expression that results in carcinogenesis. Further, though arsenic is nonmutagenic, it interacts synergistically with genotoxic agents in the production of mutations, and also induces chromosomal abnormalities and cell proliferation. Some epidemiological investigations in the arsenic endemic regions have established that inorganic arsenicals have strong potential to cause skin, bladder and lung cancers in humans. Although the adverse health effects arising from exposure to arsenic has been well-recognized, the mechanism(s) of action responsible for the diverse range of health effects are complicated and poorly understood.26?30.
Arsenic binding to cellular proteins presents a plausible mechanism of toxicity and from the mechanistic standpoint, there are two hypothesis that; a) inorganic arsenate (HAsO42?), which is a molecular analog of phosphate (HPO42?), can compete for phosphate anion transporters and replace phosphate in some biochemical reactions; b) the toxicity of trivalent arsenicals likely occurs through the interaction of trivalent arsenic species with sulfhydryl groups in proteins. Arsenic binding to a specific protein could alter the conformation and function of the protein as well as its recruitment of and interaction with other functional proteins. Therefore, there has been much importance on studies of arsenic binding to proteins, for the understanding of the arsenic toxicity and designing arsenic-based therapeutics. This chapter summarizes numerous traits of arsenic binding to proteins with a distinct emphasis to the chemical basis, biological implications and physiological consequences.
Different forms of Arsenic:
Arsenic (As) is a ubiquitous trace metalloid found in virtually all environmental media .Arsenic occurs mainly as inorganic species in natural systems. Arsenite As(III), arsenate As(V), organic arsenic and elemental arsenic are the most observed arsenic species in the world. Arsenite III is the most predominating species under anaerobic condition. whereas Arsenate V is the most stable species under aerobic conditions.,. Methylation of inorganic arsenic is generally mediated by aerobic and anerobic microorganisms leading to the formation of monomethylarsenous acid (MMAA (V)), dimethylarsinic acid (DMAA(V)), and trimethylarsine oxide (TMAO(V). Formation of volatile arsine, like monomethylarsine (MMA(-III)), dimethylarsine (DMA(-III)), and trimethylarsine (TMA(-III) takes place under anaerobic conditions.. Other Complicated organic forms of arsenic include arsenocholine (AsC), arsenobetaine (AsB), , and arsenosugars. One of the common source of organic Arsenic in the topsoil involves the use of organic As in herbicides and pesticidesAnother source of Phenyl As found in the environment is its use as chemical warfare agents and its improper treatment,storage and disposal.. Reference3——–TABLE 1