Selenosugars are key and urinary metabolites for selenium excretion within the required to low-toxic range.
Essential micronutrient selenium is excreted into the urine andor expired after being transformed to methylated metabolites. Monomethylated selenium is excreted into the urine in response to a supply within the required to low-toxic range, whereas tri- and dimethylated selenium increase with excessive supply at a toxic dose. Here we show that the major urinary selenium metabolite within the required to low-toxic range is a selenosugar. The structure of 1beta-methylseleno-N-acetyl-d-galactosamine was deduced from the spectroscopic data and confirmed by chemical synthesis. This metabolite was also detected in the liver, and an additional metabolite increased with inhibition of methylation. The latter metabolite was again a selenosugar conjugated with glutathione instead of a methyl group and was assumed to be a precursor for methylation to the former metabolite. A metabolic pathway for the urinary excretion of selenium, i.e., from the glutathione-S-conjugated selenosugar to the methylated one, was proposed. Urinary monomethylated (selenosugar) and trimethylated selenium can be used as specific indices that increase within the required to low-toxic range and with a distinct toxic dose, respectively.
Kobayashi
Yayoi
Y
Departments of Toxicology and Environmental Health, Graduate School of Pharmaceutical Sciences, Chiba University, Inage, Chiba 263-8522, Japan.
Ogra
Yasumitsu
Y
Ishiwata
Kazuya
K
Takayama
Hiromitsu
H
Aimi
Norio
N
Suzuki
Kazuo T
KT
D000116:Acetylgalactosamine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000652:urine*; D000818:Animals; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008745:Methylation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000652:urine*; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000493:pharmacokinetics / Q000633:toxicity / Q000652:urine*; D018038:Sodium Selenite / Q000008:administration & dosage / Q000493:pharmacokinetics; D021241:Spectrometry, Mass, Electrospray Ionization
C470577:1-methylseleno-N-acetylgalactosamine; D016566:Organoselenium Compounds; D005978:Glutathione; D012643:Selenium; D018038:Sodium Selenite; D000116:Acetylgalactosamine