The 31PNMR spectra of lenses from diabetic rats, show ATP,P1, glycerophosphoryl choline, alpha-glycerol phosphate, and two unusual phosphorylated metabolites resonating at 5.8 ppm and 6.5 ppm. In the normal rat lens the concentration of the 6.5 ppm compound is much lower and the 5.8 ppm compound is undetectable. The increase in the concentrations of these metabolites in the diabetic rat lens is correlated with activation of the aldose reductase pathway since it can be inhibited with an aldose reductase inhibitor sorbinil. Using normal calf lenses as a source we have purified one of these compounds (6.5 ppm) and identified it as sorbitol-3-phosphate by utilizing a variety of NMR techniques. This proposal outlines a plan for purification and characterization of the second compound (5.8 ppm). In addition, we plan to study the biosynthesis of these two compounds and to undertake initial studies on the possible correlation between them and diabetic cytopathy in the lens.
| Petersen, A; Kappler, F; Szwergold, B S et al. (1992) Fructose metabolism in the human erythrocyte. Phosphorylation to fructose 3-phosphate. Biochem J 284 ( Pt 2):363-6 |
| Szwergold, B S; Kappler, F; Brown, T R (1990) Identification of fructose 3-phosphate in the lens of diabetic rats. Science 247:451-4 |
| Petersen, A; Szwergold, B S; Kappler, F et al. (1990) Identification of sorbitol 3-phosphate and fructose 3-phosphate in normal and diabetic human erythrocytes. J Biol Chem 265:17424-7 |
