The long term objective is to clarify at the chemical level the form, fate, and function of selenium in the diet, in its role as an essential nutrient and as a modifier of environmental hazards. There is great interest in supplementing the human dietary intake of selenium to correct nutritional deficiencies, or in regard to intervention with the objective of modifying the carcinogenic process. The most critical medical use for selenium is to correct the deficiency that develops with long term total parenteral nutrition. Because of the limited knowledge about forms of selenium, metabolic transformations, and detoxification or excretory metabolites, the present study aims to identify forms of selenium that are excreted in human urine, and clarify the quantitative importance and metabolic origins of trimethylselenonium, the only known urinary metabolite. Another objective is to investigate the pathways by which known forms of selenium that are consumed by humans in food (selenoamino acids) or supplemental forms (sodium selenite) are metabolized to excretory products. The basis for the instability of sodium selenite added to TPN formulas will be investigated so that a better basis for correcting Se deficiency in long term uses of TPN can be developed. A cadmium-binding protein that may be involved in cadmium-induced injury to the microvascular system of testis, which is prevented by selenium, will be purified further and characterized. The methods for fractionating urine involve initial separation into cationic and anionic forms. Separation of cationic compounds will be done by HPLC. An important strategy is to reduce all urinary inorganic Se and compounds of the type R-Se(O)nH(n=0-2) to selenols, then convert these to R-Se-DNP derivatives for characterization by HPLC and mass spectrometry. Once the nature of R is established, model compounds of the type R-Se(0)nH will be synthesized for comparison to the unknown urinary metabolites.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
2R01AM014184-16
Application #
3150903
Study Section
Nutrition Study Section (NTN)
Project Start
1977-12-01
Project End
1988-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
16
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Earth Sciences/Resources
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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Vadhanavikit, S; Ganther, H E (1988) Nutritional availability and chronic toxicity of selenocyanate in the rat. J Nutr 118:718-22
Kinoshita, C M; Ganther, H E (1988) Isolation of a novel rat testicular metalloprotein binding cadmium and zinc. Biol Trace Elem Res 17:189-206
Ganther, H E; Kraus, R J (1987) Hydrogen selenide and methylselenol. Methods Enzymol 143:32-8
Ganther, H E; Kraus, R J; Foster, S J (1987) Trimethylselenonium ion. Methods Enzymol 143:195-201
Vadhanavikit, S; Kraus, R J; Ganther, H E (1987) Metabolism of selenocyanate in the rat. Arch Biochem Biophys 258:1-6
Foster, S J; Kraus, R J; Ganther, H E (1986) The metabolism of selenomethionine, Se-methylselenocysteine, their selenonium derivatives, and trimethylselenonium in the rat. Arch Biochem Biophys 251:77-86
Foster, S J; Kraus, R J; Ganther, H E (1986) Formation of dimethyl selenide and trimethylselenonium from selenobetaine in the rat. Arch Biochem Biophys 247:12-9
Kraus, R J; Foster, S J; Ganther, H E (1985) Analysis of trimethylselenonium ion in urine by high-performance liquid chromatography. Anal Biochem 147:432-6