Selenosugars are key and urinary metabolites for selenium excretion within the required to low-toxic range

Abstract

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.

Fig 1.

Chemical synthesis of the major urinary selenosugar.

Fig 2.

Electrospray-positive mass spectrum of hepatic Se metabolite A. The metabolite A fraction was separated on a Shodex Asahipak GS-320 HQ column by elution with 10 mM ammonium acetate, pH 7.4. (a) Full-scan spectrum for the parent ion. (b and c) Enlarged parent ions comprising the Se-characteristic isotope pattern.

Fig 3.

Electrospray-negative mass spectrum of hepatic Se metabolite A. The metabolite A fraction was separated on a Shodex Asahipak GS-320 HQ column by elution with 10 mM ammonium acetate, pH 7.4. (a) Full-scan spectrum for the parent ion. (b and c) Enlarged parent ions comprising the Se-characteristic isotope pattern.

Fig 4.

Collision-induced dissociation mass spectra (ESI-MS/MS) of the Se-containing positive molecular ions for hepatic Se metabolite A with m/z 591. (a) The proposed structure for hepatic Se metabolite A. Dissociation of the major Se-containing molecular ion, i.e., 591 (⁸⁰Se), was induced in the collision cell with 20- (b) and 40-eV (c) collision energy, and the corresponding fragment ions were detected with the second mass spectrometer.

Fig 5.

Proposed metabolic pathway for selenosugars. GSSeH, GSH selenopersulfide; SeCys, selenocysteine; SeMet, selenomethionine; SAM, S-adenosylmethionine; SAH, S-adenosylhomocysteine.