A novel enzyme that phosphorylates the Amadori product fructoselysine to fructoselysine-3-phosphate (FL3P) has been identified. FL3P is an unstable compound that decomposes to lysine, inorganic phosphate and 3- deoxyglucosone (3-DG). 3-DG is a potent protein crosslinking agent and a precursor to advanced glycation end products (AGEs). Results in normal rats suggest that increasing the flux through this new kinase with a glycated protein diet produces retinal and kidney changes similar to those seen in diabetic animals, even though blood glucose remains normal. The applicant believes that the damage seen is induced by glycation from the elevated concentration of 3-DG, and this is the first example of this type of damage in a non-diabetic animal. Therefore, this enzyme could potentially be a new therapeutic target for treatment of diabetic complications. The applicant seeks support to carry out the steps necessary to isolate this enzyme as the first step in determining its importance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DK055079-01
Application #
2794816
Study Section
Special Emphasis Panel (ZRG2-NMS (01))
Program Officer
Linder, Barbara
Project Start
1998-09-30
Project End
2000-08-31
Budget Start
1998-09-30
Budget End
1999-08-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Fox Chase Cancer Center
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19111