Metabolic transformation of methylseleninic acid through key selenium intermediate selenide.

Methylseleninic acid (MSA(IV)) [CH(3)Se(O)OH] is readily reducible to methylselenol [CH(3)SeH], the assumed lyase metabolite and the proposed biologically active form of methylated selenoamino acids. At the same time, MSA(IV) is an oxidation product of the major urinary metabolite selenosugar. (77)Se-Enriched MSA(IV) was injected intravenously into rats (25 microg 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 (77)Se were determined together with speciation analysis of the labeled metabolites. (77)Se was mostly moved into red blood cells (RBCs) within 10 min, and then redistributed into organs within 30 min. Excessive (77)Se taken up by the liver was first detected as selenosugar A and then as B, suggesting that MSA(IV) was transformed to selenide, and then to selenosugar A followed by methylation to selenosugar B (urinary metabolite). (77)Se was incorporated also into selenoproteins (most efficiently to plasma selenoprotein P that is synthesized in liver), suggesting that MSA(IV) is utilized for the synthesis of selenosugar (for excretion) and selenoproteins (for utilization) through selenide. In vitro experiments with simultaneous incubation of (77)Se-MSA(IV) and (82)Se-selenite in a RBC suspension revealed the precise difference in the metabolism between MSA(IV) and selenite in RBCs. (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(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.