It is proposed to conduct an interrelated series of experiments to elucidate the biochemical mechanism of the antagonism of the nutritional utilization of selenium (Se) by mercaptans. The project developed out of our interest in metabolic and nutritional responses to Se with likely involvement of Se-dependent factors other than the only well characterized one (Se-dependent glutathione peroxidase, SeGSHpx). In preliminary work, in which mercaptan compounds, recently shown to be potent inhibitors of SeGSHpx in vitro, were tested in vivo, several were found to reduce tissue activities activities of SeGSHpx and to potentiate clinical signs of Se-deficiency. Because the in vivo effect on SeGSHpx is not explainable by direct inhibition of the enzyme, it is of interest to learn the mechanism involved and whether it also involves more general aspects of Se metabolic function. Therefore, this project was designed to address these questions with regard to the immediate implications to the health of populations with limited Se intakes. If the antagonism of Se by mercaptans is not specific for SeGSHpx, as hypothesized, then the activities of these compounds may have important implications to the treatment of selenosis. The experiments in this plan use established animal models and biochemical methods. Two mercaptans. D-(-)-penicillamine and beta-mercaptopyruvate, will be used as model mercaptans. Because the former is also a chelator of Cu, experiments will be conducted to partition effects on Cu and/or Zn from those on Se utilization. The results can be expected to yield information relevant to both the mode of action of mercaptans and the metabolic function of Se.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK038903-02
Application #
3238485
Study Section
Nutrition Study Section (NTN)
Project Start
1988-05-01
Project End
1991-04-30
Budget Start
1989-05-01
Budget End
1990-04-30
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Cornell University
Department
Type
Earth Sciences/Resources
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850