Dietary selenium (Se) and copper (Cu) interact to affect homocysteine metabolism in rats

Abstract

Previously we reported that both Se deficiency (SeD) and Cu deficiency (CuD) decreased plasma homocysteine (pHcys) and increased plasma glutathione (pGSH) in rats. We also showed that the catalytic subunit of glutamate‐cysteine ligase (Gclc), which catalyzes the rate limiting step in glutathione biosynthesis, was upregulated in SeD as well as in CuD. We suggested that in both deficiencies, that Hcys was being shunted through the transsulfuration pathway as a result of this upregulation. Because both SeD and CuD have similar effects, we hypothesized that a combined deficiency would exacerbate the decrease in pHcys and the increase in pGSH by further upregulating Gclc. In a 2 × 2 experiment, male weanling Sprague‐Dawley rats (N=8–10/group) were fed an amino acid‐based diet containing either 0 or 0.2 μg Se (as selenite)/g and <1 or 6 μg Cu (as Cu carbonate)/g for 5 wk. Values in the table are means±SD. Both SeD and CuD resulted in decreased pHcys; however, CuD in rats fed 0.2 μg Se/g resulted in a greater decrease in pHcys than did CuD in the SeD rats. SeD and CuD resulted in increased pGSH and the combined deficiencies further exacerbated the increase. Plasma cysteine (pCys) was decreased by SeD and increased by CuD.The findings show that a combined deficiency of both Se and Cu results in lower pHcys and significantly elevated pGSH most likely as a result of increased GSH biosynthesis subsequent to upregulation of Gclc.