Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/5/2002
Publication Date: 6/1/2002
Citation: Uthus, E.O., Yokoi, K., Davis, C.D. 2002. Selenium deficiency in Fisher-344 rats decreases plasma and tissue homocysteine concentrations and alters plasma homocysteine and cysteine redox status. Journal of Nutrition. 132:1122-1128.
Interpretive Summary: Growing evidence suggests that increased plasma homocysteine is correlated with an increased risk of cardiovascular disease. There are several nutrients (vitamin B12 and folic acid, for example) that are important for the metabolism of homocysteine. Homocysteine is derived from the essential amino acid methionine. Deficiencies of these nutrients can result in a marked increase in plasma homocysteine and hence, an increased risk of cardiovascular disease. Thus, it is important to know what other dietary factors can influence the plasma concentration of homocysteine. We show that dietary selenium can affect the concentration of plasma and tissue homocysteine in laboratory rats; a lower selenium status results in a lower concentration of tissue and plasma homocysteine. Along with the decreases in tissue and plasma homocysteine, as a result of low dietary selenium, are changes in the metabolism of homocysteine and hence methionine metabolism. For example, selenium deficiency results in a decrease in the activity of one liver enzyme that is important in removing homocysteine by converting it back into methionine. This does not result in a detrimental increase in plasma homocysteine because another route of homocysteine degradation is apparently increased. Because of this, the concentration of tissue and plasma cysteine, another important amino acid in methionine metabolism, is decreased. Thus, although the decrease in plasma and tissue homocysteine as a result of selenium deficiency may appear beneficial, the concomitant decrease in plasma and tissue cysteine may be detrimental. Also, a basal level of homocysteine is needed. The results suggest that selenium deprivation is detrimental to the metabolism of methionine.
Technical Abstract: The present study determined the effect of graded amounts of dietary selenium on plasma and tissue parameters of methionine metabolism including homocysteine. Male weanling Fisher-344 rats were fed a selenium-deficient (<2 ng Se/g diet), torula yeast-based diet, supplemented with 0 (selenium deficient), 0.02 (deficient-marginal deficient), 0.05 (marginal deficient- marginal adequate) or 0.1 ug (adequate) selenium (as selenite)/g diet. After 61 d plasma total homocysteine and cysteine were significantly (p<0.0001) decreased and glutathione significantly (p<0.0001) increased by selenium deprivation. The concentration of homocysteine in kidney and heart was decreased (p=0.02) by selenium deficiency. Urinary inorganic sulfate was not affected by dietary selenium. The activities of liver betaine homocysteine methyltransferase, methionine synthase, S-adenosylmethionine synthase, and cystathionine synthase were determined; selenium deficiency affected only betaine homocysteine methyltransferase, which was decreased (p<0.0001). The ratios of plasma free reduced homocysteine (or cysteine) to free oxidized homocysteine (or cysteine) or to total homocysteine (or cysteine) were increased by selenium deprivation suggesting that selenium deprivation affects the normally tightly controlled redox status of these thiols. Although the mechanism leading to a decrease in plasma homocysteine as a result of selenium deficiency is unknown, it is evident that selenium status can affect methionine metabolism while apparently not greatly affecting the net flux of methionine to inorganic sulfate. The metabolic consequences of a marked decrease in plasma homocysteine are smaller but significant decreases in tissue homocysteine are not known.