The enzymes which synthesize and the metabolic pathways which utilize carbamyl phosphate will be studied principally in mammals.
The aim of the studies is to understand the regulation of the pathways, namely, arginine (and urea) and UMP biosynthesis. It is hoped that such studies for urea biosynthesis will be useful in acute ammonia intoxication. In the case of the UMP biosynthetic pathway, it is clear that the levels of these enzymes vary greatly due both to differentiation and development, so that tissues which divide rapidly such as cancers, regenerating and normal liver, brain, etc., have high levels of these enzymes. We would also like to see if the enzymes can be """"""""induced"""""""" and """"""""repressed,"""""""" or if increased levels are merely the result for enzyme stabilization. Studies will involve purification and kinetic characterization of isolated enzymes of both pathways or the enzyme complexes of the UMP pathway, and studies on the in vivo metabolic control of these mammalian enzymes during growth, differentiation, or when changes in nutritional or hormonal states occur in normal individual as well as studies of abnormal tissues such as cancer or mutant cells. Former work on the aspartate transcarbamylases of Streptococcus faecalis and Citrobacter freundii may be continued, as well as work on the activator of the yeast carbonic anhydrase.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK035046-10
Application #
3233281
Study Section
Biochemistry Study Section (BIO)
Project Start
1978-09-01
Project End
1989-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
10
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599