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. 2009 Nov;117(11):1724-9.
doi: 10.1289/ehp.0900734. Epub 2009 Jul 31.

Influence of Cobalamin on Arsenic Metabolism in Bangladesh

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Free PMC article

Influence of Cobalamin on Arsenic Metabolism in Bangladesh

Megan N Hall et al. Environ Health Perspect. .
Free PMC article

Abstract

Background: Arsenic is a carcinogen to which 35 million people in Bangladesh are chronically exposed. The enzymatic transfer of methyl groups to inorganic As (iAs) generates monomethylarsonic (MMA) and dimethylarsinic acids (DMA) and facilitates urinary As (uAs) elimination. This process is dependent on one-carbon metabolism, a pathway in which folate and cobalamin have essential roles in the recruitment and transfer of methyl groups. Although DMA(V) is the least toxic metabolite, increasing evidence suggests that MMA(III) may be the most cytotoxic and genotoxic As intermediary metabolite.

Objective: We examined the associations between plasma cobalamin and uAs metabolites.

Methods: We conducted a cross-sectional study of 778 Bangladeshi adults in which we over-sampled cobalamin-deficient participants. Participants provided blood samples for the measurement of plasma cobalamin and urine specimens for As measurements.

Results: Cobalamin was inversely associated with the proportion of total uAs excreted as iAs (%iAs) [unstandardized regression coefficient (b) = -0.10; 95% confidence interval (CI), -0.17 to -0.02; p = 0.01] and positively associated with %MMA (b = 0.12; 95% CI, 0.05 to 0.20; p = 0.001). Both of these associations were stronger among folate-sufficient participants (%iAs: b = -0.17; 95% CI, -0.30 to -0.03; p = 0.02. %MMA: b = 0.20; 95% CI, 0.11 to 0.30; p < 0.0001), and the differences by folate status were statistically significant.

Conclusions: In this group of Bangladeshi adults, cobalamin appeared to facilitate the first As methylation step among folate-sufficient individuals. Given the toxicity of MMA(III), our findings suggest that in contrast to folate, cobalamin may not favorably influence As metabolism.

Keywords: Bangladesh; arsenic; cobalamin; creatinine; dimethylarsinic acid; folate; homocysteine; monomethylarsonic acid; one-carbon metabolism.

Figures

Figure 1
Figure 1
Arsenate is reduced to arsenite in a reaction thought to be dependent on GSH or other endogenous reductants. Arsenite then undergoes an oxidative methylation, with SAM as the methyl donor, forming MMAV and SAH. MMAV is reduced to MMAIII and then undergoes a subsequent oxidative methylation step to produce DMAV and SAH.
Figure 2
Figure 2
Methylation of arsenite by methyl-cobalamin by incubation time and molar ratio of CH3B12:AsIII at pH 7.4. AsIII and CH3B12 were combined in Tris-HCl buffer in the presence of GSH, and aliquots were analyzed by HPLC-ICP-MS over time.

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