title: Dietary selenium (Se) and copper (Cu) interact to affect homocysteine metabolism in rats.
abstract: Previously, we reported that both Se deficiency and Cu deficiency 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 Se and Cu deficiencies. We suggested that in both deficiencies, Hcys was being shunted through the trans-sulfuration pathway as a result of this up-regulation. Because both Se and Cu deficiencies have similar effects, we hypothesized that a combined deficiency would exacerbate the decrease in pHcys and the increase in pGSH by further up-regulating Gclc. In a 2 x 2 experiment, male weanling Sprague-Dawley rats (n = 8-20/group) were fed an amino-acid-based diet containing either 0 or 0.2 microg Se (as selenite)/g and <1 or 6 microg Cu (as Cu carbonate)/g for 5 weeks. Our findings show that a combined deficiency of both Se and Cu results in lower pHcys and significantly elevated pGSH. However, the up-regulation of liver Gclc alone cannot explain why rats fed with the doubly deficient diet have the lowest pHcys and the highest pGSH.
authors.affiliation: Grand Forks Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Grand Forks, ND 58202-9034, USA. eric.uthus@ars.usda.gov
authors.forename: Eric O
authors.initials: EO
authors.lastname: Uthus
authors.forename: Sharon
authors.initials: S
authors.lastname: Ross
mesh_terms: D000821:Animal Feed; D000818:Animals; D003300:Copper / Q000008:administration & dosage* / Q000172:deficiency / Q000494:pharmacology*; D004347:Drug Interactions; D005978:Glutathione / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012435:S-Adenosylhomocysteine / Q000737:chemistry / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000737:chemistry / Q000378:metabolism; D012643:Selenium / Q000008:administration & dosage* / Q000172:deficiency / Q000494:pharmacology*
chemical_list: D003300:Copper; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D005978:Glutathione; D012643:Selenium