Methods for alleviating deleterious effects of 3-deoxyglucosone
View Patent ↗Disclosed is a class of compounds which inhibit the enzymatic conversion of fructose-lysine into fructose-lysine-3-phosphate in an ATP dependent reaction in a newly discovered metabolic pathway. According to the normal functioning on this pathway, fructose-lysine-3-phosphate (FL3P) is broken down to form free lysine, inorganic phosphate and 3-deoxyglucosone (3DG), the latter being a reactive protein modifying agent. 3DG can be detoxified by reduction to 3-deoxyfructose (3DF), or it can react with endogenous proteins to form advanced glycation end-product modified proteins (AGE-proteins) Also disclosed are therapeutic methods of using such inhibitors to alleviate deleterious effects of 3DG.
1. A method of alleviating the deleterious effects of aging in a diabetic patient in need thereof, said effects being due to the production of 3DG by the enzymatic conversion of fructose-lysine (FL) to fructose-lysine-3-phosphate (FL3P), said method consisting of administering to said patient as the sole therapeutic agent an effective amount of an inhibitor of said enzymatic conversion of FL to FL3P, said inhibitor being a compound selected from the group consisting of sorbitollysine, mannitollysine, galactitollysine, 3-O-methyl sorbitollysine, meglumine and the pharmaceutically acceptable salts thereof.
2. The method of claim 1 , wherein said inhibitor is meglumine or a pharmaceutically acceptable salt thereof.
3. The method of claim 1 , wherein said inhibitor is administered in solid form, also comprising a pharmaceutically acceptable excipient.
4. The method of claim 1 , wherein said inhibitor is administered in liquid form, also comprising a pharmaceutically acceptable diluent.
5. The method of claim 1 , wherein said inhibitor is administered at a dosage level of about 0.7μg to about 20 mg of said inhibitor per kilogram of patient body weight per day.
6. The method of claim 5 , wherein said dosage level is from about 30 μg to about 3.5 mg of said inhibitor per kilogram of patient body weight per day.
7. The method of claim 1 , wherein said inhibitor is administered via a route selected from the group of oral, parenteral, intraperitoneal, or intravenous administration.