The long-term objective is to clarify at the chemical level the fate of selenium in living organisms. This information is needed to better understand its functions as an essential trace element, its anticarcinogenic action, and toxic effects of excess selenium. There is great interest in supplementing the human diet with selenium to correct nutritional deficiencies or improve oxidant defense mechanisms, and recent human cancer chemoprevention trials also have used selenium supplementation. There is rather limited knowledge about forms of selenium in tissues, and the mechanisms by which inorganic forms of selenium such as sodium selenite or selenate are firmly and selectively incorporated into proteins. There is evidence that selenoaminoacids are formed, even in proteins that do not appear to have mechanisms for inserting selenocysteine by cotranslational processes; these selenoaminoacids typically show divergence in their chromatographic properties from the known selenoaminoacids, and tend to be found with the more hydrophobic residues. It is the purpose of this study to clarify the nature of the selenoaminoacids or related forms found in proteins of animals following in vivo or in vitro labeling with radioactive inorganic selenium. The hypothesis to be tested is that selenium is metabolized to reactive intermediates that bind covalently to protein targets. These proteins may selectively labeled because of their proximity to the site where the reactive intermediates are generated, as well as having certain types of aminoacid residues (hydrophobic) that are more likely to undergo reactions with the reactive selenium intermediates. It is emphasized that in long-term dietary supplementation of humans with selenium, these modification reactions may be significant in regard to certain biological effects of selenium such as anticarcinogenic action, as well as undesirable toxic side effects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK014184-24
Application #
2136830
Study Section
Nutrition Study Section (NTN)
Project Start
1977-12-01
Project End
1998-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
24
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Nutrition
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Ganther, H E (2001) Selenotyrosine and related phenylalanine derivatives. Bioorg Med Chem 9:1459-66
Vadhanavikit, S; Ganther, H E (1994) Selenium deficiency and decreased coenzyme Q levels. Mol Aspects Med 15 Suppl:s103-7
Vadhanavikit, S; Ganther, H E (1993) Selenium requirements of rats for normal hepatic and thyroidal 5'-deiodinase (type I) activities. J Nutr 123:1124-8
Vadhanavikit, S; Ganther, H E (1993) Decreased ubiquinone levels in tissues of rats deficient in selenium. Biochem Biophys Res Commun 190:921-6
Ganther, H E; Kraus, R J (1989) Chemical stability of selenious acid in total parenteral nutrition solutions containing ascorbic acid. JPEN J Parenter Enteral Nutr 13:185-8
Ip, C; Ganther, H (1988) Efficacy of trimethylselenonium versus selenite in cancer chemoprevention and its modulation by arsenite. Carcinogenesis 9:1481-4