blood Hg, plasma HCY, MMA, folate in US children aged 3-5 years, NHANES 1999-2004

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Some of the article's cites are hereinbelow:

Total blood mercury, plasma homocysteine, methylmalonic acid and folate

in US children aged 3-5years, NHANES 1999-2004.

<http://www.ncbi.nlm.nih.gov/pubmed/21295329>

Gallagher CM, Meliker JR.

Sci Total Environ. 2011 Feb 2.

BACKGROUND: Mercury is a known neurotoxicant; however, the relationship

between childhood exposures and neurodevelopmental outcomes is

uncertain, and may be modified by nutrition-related susceptibilities. In

vitro studies found that mercury inhibited methionine synthase, an

enzyme that interacts with vitamin B-12 and folate to regenerate the

amino acid methionine from homocysteine, and inhibition of methionine

synthase diverted homocysteine to cysteine and glutathione synthesis.

The relationships between mercury, homocysteine, B-12, and folate have

not been examined in children.

OBJECTIVE: This study aimed to evaluate associations between Hg and

homocysteine in male and female children differentiated by higher and

lower methylmalonic acid (MMA, an indicator of vitamin B-12 deficiency)

and folate status.

DESIGN: Cross-sectional data on total blood mercury (Hg), plasma

homocysteine, MMA, and serum folate were obtained from the 1999-2004

National Health and Nutrition Examination Surveys for children aged

3-5years (n=1005). We used multiple linear regression to evaluate

relationships between homocysteine and Hg quartiles, stratified by sex,

MMA ? and folate < sample medians, adjusted for demographic,

anthropometric, and environmental factors.

RESULTS: In boys with higher MMA and lower folate (n=135), but not in

other children, we observed inverse associations between homocysteine

and Hg. Children with Hg>3.49?mol/L showed 1.14?mol/L lower homocysteine

(p<0.001) relative to the lowest quartile (?0.70?mol/L) {p-value for

trend<0.001}. Compared to other subsamples, this subsample had

significantly higher homocysteine levels.

CONCLUSION: Hg was inversely correlated with plasma homocysteine in

young boys, but not girls, with higher MMA and lower folate. Additional

studies are merited to evaluate Hg and amino acid metabolism in

susceptible children.

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1. Introduction

Mercury is a known neurotoxicant (ATSDR, 1999; NRC, 2000; EFSA,

2004); however, the relationship between childhood exposures and

neurodevelopmental outcomes is uncertain (Myers and son,

2000; Aschner and Ceccatelli, 2010), andmay be modified by nutritionrelated

susceptibilities (US EPA, 1997; Myers and son, 2000;

Dufault et al., 2009a). People are exposed to different forms of mercury,

including organic (methyl- or ethylmercury), inorganic, or metallic;

neurologic damage is evident at sufficient levels of exposure tometallic

mercury vapors and some organicmercury compounds (ATSDR, 1999).

Although a general mechanism of toxicity is the binding of mercury to

exposed cysteine residues on proteins (Wang and Horisberger, 1996; Li

et al., 2007; Klaassen, 2008), its precise mechanism of toxicity has not

yet been elucidated, especially at low levels of exposure.

One possible mechanism of mercury's actions involves alteration

in metabolic processes critical to human neuronal cell function by

inhibiting methionine synthase (Waly et al., 2004), an enzyme that

interacts with vitamin B-12 and folate to regenerate the amino acid

methionine from homocysteine (Deth et al., 2008; , 2010). The

vitamin B-12 and folate-dependent methionine cycle supports the

transsulfuration pathway for the metabolism of the amino acids

homocysteine and cysteine to glutathione, an anti-oxidant that

protects cells against oxidative stress (Ercal et al., 2001). Experimental

studies have also shown that mercury inhibits cysteine transport to

and uptake in brain cells (-Willis et al., 2002; Shanker et al.,

2001) and decreases neuronal glutathione levels ( et al., 2005).

Therefore, mercury may interact with nutritional factors to alter

metabolic processes of the methionine cycle and transsulfuration

pathway that influence neuronal cell function. Because homocysteine

bridges the methionine cycle and transsulfuration pathway, changes

in homocysteine levels may provide a biochemical indication of

impaired amino acid metabolism. Lee et al. (2009) hypothesized that

low dose chemical exposures increase the demand for glutathione,

and so, divert homocysteine from methionine remethylation to

glutathione synthesis, with resultant reductions in homocysteine

availability for metabolic homeostasis. Inhibition of methionine

synthase activity has been shown to divert homocysteine to cysteine

and glutathione production in human lens epithelial cells (Persa et al.,

2004); therefore, findings that mercury inhibited methionine

synthase function in human neuronal cells (Waly et al., 2004) suggest

the potential for an inverse relationship between mercury and

homocysteine (Deth et al., 2008).

Gender differences have been shown with regard to metal toxicity

and homocysteine levels....

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