Metabolism of fructose-3-phosphate in the diabetic rat lens.
Fructose-3-phosphate and sorbitol-3-phosphate are produced in diabetic rat lenses by a 3-phosphokinase. While sorbitol-3-phosphate appears to be an inert polyol phosphate, fructose-3-phosphate is a potent cross-linking agent and a potential in vivo source of 3-deoxyglucosone. The objective of this study was to investigate the production and decomposition of fructose-3-phosphate in the diabetic rat lens. The results indicate that this metabolite achieves a steady-state concentration of almost 1 mumol/g wet weight within 2 weeks after the onset of diabetes. These steady-state levels appear to be a consequence of a balance between its production from fructose and its further decomposition to 3-deoxyglucosone. This conclusion is supported by results from disappearance of fructose-3-phosphate in insulin-treated diabetic rats and in vitro incubations of fructose-3-phosphate with amines where production of 3-deoxyglucosone was detected using a number of different methods including mass spectrometry. In agreement with these results, elevated concentrations of 3-deoxyglucosone along with its detoxification product, 3-deoxyfructose, were detected in the diabetic rat lenses. Other sugars and sugar phosphates which were detectable in the diabetic rat lenses were glucose, fructose, glucose-6-phosphate, fructose-6-phosphate, and sedoheptulose-7-phosphate. In conclusion, results from this study suggest that fructose-3-phosphate and 3-deoxyglucosone are likely to be important contributors to the process of nonenzymatic glycation in diabetic rat lenses.
Lal
S
S
Department of NMR and Medical Spectroscopy, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Szwergold
B S
BS
Taylor
A H
AH
Randall
W C
WC
Kappler
F
F
Wells-Knecht
K
K
Baynes
J W
JW
Brown
T R
TR
D000818:Animals; D050260:Carbohydrate Metabolism; D003459:Crystallins / Q000378:metabolism; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005636:Fructosephosphates / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006031:Glycosylation; D006600:Hexosephosphates / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013403:Sugar Phosphates / Q000378:metabolism
D003459:Crystallins; D005636:Fructosephosphates; D006600:Hexosephosphates; D013403:Sugar Phosphates; C059844:sorbitol 3-phosphate; C062519:fructose 3-phosphate; D003847:Deoxyglucose; C016350:3-deoxyglucosone