Arsenic oxidation pathways

IV. OXIDATION PATHWAYS OF ARSENIC (III) TO ARSENIC (V) IN SOILS AND NATURAL WATERS... 

According to Challenger (127), arsenate is transformed to trimethyl-arsine by the mold Scopulariopsis brevicaulis, by sequential reduction and oxidative methylation of the arsenic species (Fig. 7). The proposed intermediates in the pathway were MMA, DMA, and TMAO. Although Challenger could not detect these compounds, when they were added to a culture of S. brevicaulis trimethylarsine was formed. Challenger (129) considered that the likely source of methyl groups was S-adeno-sylmethionine (AdoMet), which had previously been identified as an... 

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). 

This scheme does not link the oxidation of As(III) with methylation and posits that the obligatory substrate for methylation is an As(III)-GSH complex. In a related analysis of AS3 ATT-catalyzed methylation, it has been suggested that As(III) bound to cellular proteins are the substrates for methylation (Naran-mandura, Suzuki and Suzuki, 2006). Because AS3MT can catalyze the methylation of inorganic As(III) in reaction mixtures that do not contain GSH, but do contain dithiol reductants, it is unclear how the presence of GSH can be considered a requirement for AS3 ATT-catal yzed methylation. In cellular environments that contain the dithiol reductants, GSH, and a plethora of proteins that could bind As(III), it is quite possible that multiple reaction pathways may be involved in the production of methylated arsenicals. Further experimental work will be required to identify each of the molecular components of these pathways. 

Henry and Thorpe [14] separated monomethylarsonic acid, dimethylarsenic acid, As(III) and As(IV) on an ion exchange column from samples of pond water receiving fly ash from a coal-fired power station. They then determined these substances by differential pulse polarography. The above four arsenic species were present in non saline water systems. Moreover, a dynamic relationship exists whereby oxidation-reduction and biological methylation-dimethylation reactions provide the pathways for the intercoversions of the arsenicals. 

One of the most intriguing reactions in the chytochrome P450 catalysis is the transfer of second electron and dioxygen activation, which appears to be a key step of the entire process. The chemical nature of reactive oxidizing species appears in the coordination sphere of heme iron and the mechanism of hydroxylation of organic compounds, saturated hydrocarbons in particular, is a much debated question in the field of the cytochrome P450 catalysis. To solve this problem, an entire arsenal of modern experimental and theoretical methods are employed. The catalytic pathway of cytochrome P450cam from Pseudomonas putida obtained on the basis of X-ray analysis at atomic resolution is presented in Fig. 3.10. 

Lewisite in soil may rapidly volatilize or may be converted to lewisite oxide due to moisture in the soil (Rosenblatt et al, 1975). The low water solubility suggests intermediate persistence in moist soil (Watson and Griffin, 1992). Both lewisite and lewisite oxide may be slowly oxidized to 2-chlorovinylarsonic acid (Rosenblatt et al, 1975). Possible pathways of microbial degradation in soil include epoxidation of the C=C bond and reductive deha-logenation and dehydrohalogenation (Morrill et al, 1985). Due to the epoxy bond and arsine group, toxic metabolites may result. Additionally, residual hydrolysis may result in arsenic compounds. Lewisite is not likely to bioaccumulate. However, the arsenic degradation products may bioaccumulate (Rosenblatt et al, 1975). 

The co-administration of M. oleifera seed powder with arsenic protects animals from arsenic induced oxidative stress and reduce body arsenic burden (49). Exposure of rats to arsenie (2.5 mg/kg, intraperitoneally for 6 weeks) increases the levels of tissue reaetive oxygen species (ROS), metallothionein (MT) and thiobarbitnrie aeid reaetive substance (TEARS) and is accompanied by a decrease in the aetivities in the antioxidant enzymes such as superoxide dismutase (SOD), eatalase and glutathione peroxidase (GPx). Also, Arsenic exposed mice exhibits hver injury as reflected by reduced acid phosphatase (AGP), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) activities and altered heme synthesis pathway as shown by inhibited blood 8-aminolevulinic acid dehydratase (5-ALAD) activity. Co-administration of M. oleifera seed powder (250 and 500 mg/kg, orally) with arsenie significantly increases the activities of SOD, catalase, GPx with elevation in redueed GSH level in tissues (liver, kidney and brain). These ehanges are accompanied by approximately 57%, 64% and 17% decrease in blood ROS, liver metallothionein (MT) and lipid peroxidation respectively in animal eo-administered with M. oleifera and arsenic. There is a reduced uptake of arsenie in soft tissues (55% in blood, 65% in liver, 54% in kidneys and 34% in brain) following eo-administration of M. oleifera seed powder (particularly at the dose of 500 mg/kg). This points to the fact that administration of M. oleifera seed powder could be beneficial during chelation therapy with a thiol chelator (26). 

Trimethylarsine oxide has been reported in several marine animals, where it is almost always a trace constituent. The one exception is the fish Kyphosus sydney-anus, which has trimethylarsine oxide as the major arsenical (25). That trimethylarsine oxide is not more widespread is perhaps surprising since it is likely to be a metabolite of the same pathway producing methylarsonate and dimethylarsinate, both of which are more commonly found. Trimethylarsine oxide chromatographs rather poorly on cation-exchange columns often used for determining arsenic species, and the resultant poor detection limits for this compound may partly explain the data indicating its apparent absence in many samples. Trimethylarsine oxide is usually only rarely reported in terrestrial organisms, but more recent work (with better detection limits) has shown it to be present in various terrestrial plants and two lichen samples (26). 

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