Dietary selenium (Se) but not folic acid (FA) affects the activity and mRNA of rat liver betaine homocysteine methyltransferase (BHMT)

Abstract

Because of up-regulation of γ-glutamylcysteine synthetase (GGCS) rodents shunt homocysteine (Hcys) to the transsulfuration pathway resulting in low plasma Hcys when Se is low. However, humans with low Se status do not appear to up-regulate GGCS and therefore place more emphasis on remethylation of Hcys for removal. Thus, dietary factors that affect remethylation of Hcys are of critical importance. We have previously shown that the activity of liver BHMT is decreased by deficient or marginally deficient Se-fed rats. Gonzalez et al (J Nutr 2004) correlated low Se status with increased Hcys in humans and suggested that this may be mediated through the effect of Se on BHMT. Here we expand our previous studies on the influence of Se on BMHT in a rodent model. Weanling, Fischer-344 rats were fed diets containing 0, 0.2, or 2 μg Se (as selenite) and 0 or 2 μg FA/g in a 3 x 2 design. After 72 d, the activity of liver BHMT was significantly decreased (p<0.001) in rats fed no supplemental Se compared to rats fed adequate or supranutritional Se; there was no difference comparing adequate vs supranutritional Se. Supplementation of FA tended (p=0.08) to decrease the activity. As determined by real-time RT PCR, liver BHMT mRNA was significantly down-regulated (p<0.002) in rats fed no supplemental Se; FA had no effect. Although the effect of Se status on BHMT in humans is not known, our results are intriguing in light of work by Gonzalez et al who suggest that serum Se may have greater effect on regulating Hcys than FA in humans and that this may be mediated through the effect of Se on BHMT.