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Title: Metabolism of selenite to selenosugar and trimethylselenonium in vivo: tissue dependency and requirement for S-Adenosylmethionine-dependent methylation

Author
item Jackson, Matthew
item LUNOE, KRISTOFFER - University Of Copenhagen
item GABEL-JENSEN, CHARLOTTE - University Of Copenhagen
item GAMMELGAARD, BENTE - University Of Copenhagen
item Combs, Gerald

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/18/2013
Publication Date: 12/2/2013
Citation: Jackson, M.I., Lunoe, K., Gabel-Jensen, C., Gammelgaard, B., Combs, G.F. 2013. Metabolism of selenite to selenosugar and trimethylselenonium in vivo: tissue dependency and requirement for S-Adenosylmethionine-dependent methylation. Journal of Nutritional Biochemistry. 24:2023-2030.

Interpretive Summary: The essential nutrient selenium (Se) is metabolized by methylation and is known to exhibit anticancer activity. However, recent clinical trials have demonstrated that not all subjects benefit from Se supplementation. The process of methylation is perturbed in obesity and aging, which might account for the variability in clinical to Se supplementation. We tested the hypothesis that a type of methylation, dependent upon S-adenosylmethionine (SAM), was required for the metabolism of Se. Our results show that liver and kidney are primary organs for metabolism of Se and that SAM dependent methylation is required for production of Se metabolites and excretion of Se. We conclude that inter-individual variation in methylation capacity might reduce metabolism of dietary Se, and that future trials involving Se supplementation should consider methylation capacity when determining efficacy.

Technical Abstract: Dietary selenium (Se) is subject to post-absorptive transformation to species having both anti-cancer activity and pro-diabetogenic potential; and its transformation is affected by availability of cofactors, substrates and/or inhibitors of methylation. Impaired S-adenosylmethionine (SAM)-dependent transmethylation and reduced methylation capacity feature in the etiology of diseases related to aging and obesity, and Se metabolism is altered in these states. In this study we tested the hypothesis that SAM-dependent transmethylation is required for methylation and excretion of selenite in an acute model that does not affect systemic markers of single-carbon status. The results show that SAM-dependent transmethylation differentially impacts metabolism of selenite into trimethylselenonium versus methylated selenosugar Se-methyl-N-acetylselenohexosamine, as reduced methylation decreases production of the former more so than it does the latter. Further, we demonstrate that hepatic and renal metabolism of selenite differs in their dependencies on transmethylation. This work suggests that low molecular weight Se metabolism requires SAM-dependent methylation, and suggests implications for selenium supplementation under conditions where transmethylation is suboptimal, such as in the case of obese or aging individuals.