title: Metabolism of selenite to selenosugar and trimethylselenonium in vivo: tissue dependency and requirement for S-adenosylmethionine-dependent methylation.
abstract: Impaired S-adenosylmethionine (SAM)-dependent transmethylation and methylation capacity feature in diseases related to obesity or aging, and selenium (Se) metabolism is altered in these states. We tested the hypothesis that SAM metabolism is required for methylation and excretion of Se in a rat model. Four hours after selenite and periodate-oxidized adenosine (POA; an inhibitor of SAM metabolism) were administered, circulating markers of single-carbon status were unchanged, except for decreased circulating phosphatidylcholine (P<.05). In contrast, liver and kidney SAM and S-adenosylhomocysteine were elevated (P<.05 for all). Concentrations of total Se were significantly elevated in both liver (P<.001) and kidney (P<.01), however the degree of accumulation in liver was significantly greater than that of kidney (P<.05). Red blood cell Se levels were decreased (P=.01). Trimethylselenonium levels were decreased in liver and kidney (P=.001 for both tissues) and Se-methyl-N-acetylselenohexosamine selenosugar was decreased in liver (P=.001). Urinary output of both trimethylselenonium (P=.001) and selenosugar (P=.01) was decreased as well. Trimethylselenonium production is more inhibited by POA than is selenosugar production (P<.05). This work indicates that low molecular weight Se metabolism requires SAM-dependent methylation, and disrupting the conversion of SAM to S-adenosylhomocysteine prevents conversion of selenite and intermediate metabolites to final excretory forms, suggesting implications for selenium supplementation under conditions where transmethylation is suboptimal, such as in the case of obese or aging individuals.
authors.affiliation: Grand Forks Human Nutrition Research Center; ARS-USDA, North Dakota, USA. Electronic address: matthew_jackson@hillspet.com.
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Jackson
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Lunøe
authors.forename: Charlotte
authors.initials: C
authors.lastname: Gabel-Jensen
authors.forename: Bente
authors.initials: B
authors.lastname: Gammelgaard
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Combs
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D019587:Dietary Supplements; D004912:Erythrocytes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008745:Methylation; D008970:Molecular Weight; D016566:Organoselenium Compounds / Q000378:metabolism* / Q000652:urine; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism*; D020887:Selenious Acid / Q000378:metabolism*; D012643:Selenium / Q000008:administration & dosage / Q000493:pharmacokinetics; D018036:Selenium Compounds / Q000378:metabolism* / Q000652:urine; D051140:Selenoproteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016566:Organoselenium Compounds; D012333:RNA, Messenger; C464429:Se-methyl-N-acetylselenohexosamine; D018036:Selenium Compounds; D051140:Selenoproteins; C027579:periodate-oxidized adenosine; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D020887:Selenious Acid; D012643:Selenium; D000241:Adenosine; C003717:trimethylselenonium
keywords: Cancer; Liver; Methylation; S-adenosylhomocysteine; S-adenosylmethionine; Selenite; Selenium; Selenosugar; Trimethylselenonium