Metabolic transformation of methylseleninic acid through key selenium intermediate selenide

Journal Article · Fri Sep 01 04:00:00 EDT 2006 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2006.02.011· OSTI ID:20850406

Suzuki, Kazuo T ^[1]; Kurasaki, Kazuki ^[1]; Ogawa, Sayaka ^[1]; Suzuki, Noriyuki ^[1]

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1. Graduate School of Pharmaceutical Sciences, Chiba University, Chuo, Chiba 260-8675 (Japan)

Methylseleninic acid (MSA{sup IV}) [CH{sub 3}Se(O)OH] is readily reducible to methylselenol [CH{sub 3}SeH], the assumed lyase metabolite and the proposed biologically active form of methylated selenoamino acids. At the same time, MSA{sup IV} is an oxidation product of the major urinary metabolite selenosugar. {sup 77}Se-Enriched MSA{sup IV} was injected intravenously into rats (25 {mu}g Se/kg body weight), and urine, blood and liver were obtained at five time points after the injection. Time-related changes in the concentration of {sup 77}Se were determined together with speciation analysis of the labeled metabolites. {sup 77}Se was mostly moved into red blood cells (RBCs) within 10 min, and then redistributed into organs within 30 min. Excessive {sup 77}Se taken up by the liver was first detected as selenosugar A and then as B, suggesting that MSA{sup IV} was transformed to selenide, and then to selenosugar A followed by methylation to selenosugar B (urinary metabolite). {sup 77}Se was incorporated also into selenoproteins (most efficiently to plasma selenoprotein P that is synthesized in liver), suggesting that MSA{sup IV} is utilized for the synthesis of selenosugar (for excretion) and selenoproteins (for utilization) through selenide. In vitro experiments with simultaneous incubation of {sup 77}Se-MSA{sup IV} and {sup 82}Se-selenite in a RBC suspension revealed the precise difference in the metabolism between MSA{sup IV} and selenite in RBCs. {sup 77}Se excreted into the urine was mostly detected as selenosugar but with a distinct amount of trimethylselenonium, suggesting that selenosugar and trimethylselenonium are produced depending on the capacity to transform methylselenol to selenide. MSA{sup IV} was suggested to be reduced to methylselenol (allowing the production of a proposed active form of selenium), and then transformed (demethylated) to selenide for utilization and excretion.

• OSTI ID: 20850406
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 215; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ARGON
BLOOD CELLS
EXCRETION
GLUTATHIONE
HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY
IN VITRO
LIVER
MASS SPECTROSCOPY
METABOLISM
METABOLITES
METHYLATION
PEROXIDASES
RATS
SELENIUM
SYNTHESIS
URINE