The Experts below are selected from a list of 14514 Experts worldwide ranked by ideXlab platform
Truman R. Brown - One of the best experts on this subject based on the ideXlab platform.
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Fructose 3 Phosphate production and polyol pathway metabolism in diabetic rat hearts
Metabolism-clinical and Experimental, 1997Co-Authors: Sundeep Lal, Francis Kappler, William C Randall, Truman R. Brown, Anne Taylor, Michael Walker, Benjamin S SzwergoldAbstract:Previous studies have suggested that polyol-pathway and nonenzymatic glycation may be involved in the development of cardiac myopathy, a well-known manifestation of diabetes. Although the exact etiology of this complication is not fully understood, it is likely to be multifactorial. In this study, we investigated the metabolic consequences of diabetes and the effect of aldose reductase inhibitor (ARI) treatment on cardiac tissues of Sprague-Dawley rats. Perchloric acid (PCA) extracts of hearts from the animals were examined using 31P-nuclear magnetic resonance (NMR), gas chromatography/mass spectrometry (GC/MS), and high-performance liquid chromatography (HPLC). In 31P-NMR spectra of diabetic animals, a peak resonating at the chemical shift of 5.8 ppm with a coupling constant of 10 Hz was identified as Fructose-3-Phosphate (F3P). Undetectable in controls (< approximately 20 nmol/g), this metabolite was present at a concentration of 81.3 +/- 16.3 nmol/g wet weight (n = 4) in diabetic rat hearts. GC/MS analysis of these extracts from diabetics also identified a decomposition product of F3P, 3-deoxyglucosone (3DG), at a concentration of 9.4 +/- 3.5 nmol/g (n = 3), compared with 0.98 +/- 0.43 nmol/g (n = 3) in controls. No evidence was found for the expected detoxification products of 3-DG, 3-deoxyFructose and 2-keto 3-deoxygluconate. Concomitant with the elevation of F3P and 3DG, Fructose and sorbitol levels were also elevated in diabetic animals. Surprisingly, ARI treatment was found to have no effect on the levels of these metabolites. These data suggest that either the heart may be unique in its production of Fructose or it may not readily transport the ARI sorbinil. Production of the potent glycating agents F3P and 3DG in diabetics suggests that these compounds may be contributing factors in the glycation of cardiac proteins in the diabetic rat heart.
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identification of galactitol 2 Phosphate and galactitol 3 Phosphate in the lens of galactose fed rats
Metabolism-clinical and Experimental, 1995Co-Authors: Francis Kappler, Bangying Su, Benjamin S Szwergold, William C Randall, Truman R. BrownAbstract:Abstract Production of unusual phosphorylated metabolites in the lens is one of several changes caused by hyperglycemia. Sorbitol 3-Phosphate (Sor-3P) and Fructose 3-Phosphate (Fru-3P) are two such compounds identified in the diabetic lens, and galactitol 2-Phosphate (Gal-2P) and galactitol 3-Phosphate (Gal-3P) are identified here in the galactosemic lens. These new compounds are the first example of galactitol metabolism in mammalian tissue other than liver. Sor-3P and Fru-3P are also present in the galactosemic lens, apparently synthesized directly from their precursors, sorbitol and Fructose, which are elevated in the lens due to increased flux of glucose through the aldose reductase (AR) pathway. The NADPH necessary to support this increased flux is derived from activation of the hexose monoPhosphate shunt (HMPS), which is clearly demonstrated by a large increase in the concentration of sedoheptulose 7-Phosphate (Sed-7P), a HMPS-specific metabolite. Additionally, during 3 weeks of galactose feeding there is a dramatic increase in lenticular concentrations of galactitol, sorbitol, galactose, and Fructose and a sharp decrease in inositol. Glucose remains unchanged. A precipitous loss of both phosphorylated and nonphosphorylated metabolites occurs after 3 weeks, possibly due to lens rupture.
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Metabolism of Fructose-3-Phosphate in the Diabetic Rat Lens
Archives of Biochemistry and Biophysics, 1995Co-Authors: Benjamin S Szwergold, Francis Kappler, William C Randall, Anne H Taylor, Kevin J. Wells-knecht, John W. Baynes, Truman R. BrownAbstract:Abstract Fructose-S-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 μmol/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.
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Production of Fructose and Fructose-3-Phosphate in maturing rat lenses.
Investigative Ophthalmology & Visual Science, 1995Co-Authors: Benjamin S Szwergold, Francis Kappler, William C Randall, Anne H Taylor, Truman R. BrownAbstract:Purpose. A large increase in glycation of crystallins between 1 and 8 months has been demonstrated in lenses obtained from aging rats. The objective of this study was to investigate if an age-associated increase in the levels of any of the phosphorylated and nonphosphorylated sugars in the aging rat lenses could be correlated with this increase. Methods. Lenses were obtained from Sprague-Dawley rats ranging in age from 2 to 20 months. Trichloroacetic extracts of these tissues were analyzed by using 31 P-NMR for sugar Phosphates and high-pressure liquid chromatography equipped with an electrochemical detector for sugars and polyols. Results. Although no elevation in the lenticular glucose levels was observed, an age-associated increase in the concentrations of polyol pathway-associated metabolites-sorbitol, Fructose, sorbitol-3-Phosphate, and Fructose-3-Phosphate-was detected. In contrast, no significant changes were observed in glycolytic or pentose shunt metabolites. Conclusion. Aging lenses accumulate increased concentrations of Fructose and Fructose-3-Phosphate. Because Fructose-3-Phosphate is a potent glycating agent and a potential in vivo source 3-deoxyglucosone, its accumulation in the lens, along with Fructose, may be a contributing factor in the age-associated increase of nonenzymatic glycation in rat lenses
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Fructose metabolism in the human erythrocyte. Phosphorylation to Fructose 3-Phosphate.
Biochemical Journal, 1992Co-Authors: A Petersen, Francis Kappler, Benjamin S Szwergold, Truman R. BrownAbstract:In human erythrocytes, the first step in the metabolism of Fructose is generally thought to be phosphorylation to Fructose 6-Phosphate catalysed by hexokinase. In variance with this assumption, we show here that Fructose in these cells is metabolized primarily to Fructose 3-Phosphate by a specific 3-phosphokinase. This process has an overall estimated Km of 30 mM with respect to extracellular Fructose and an apparent Vmax. of 0.6 mumol/h per ml. At a fixed concentration of Fructose in the medium, the accumulation of Fructose 3-Phosphate was linearly dependent on the duration of incubation up to 5 h and was not affected by glucose. Once accumulated, Fructose 3-Phosphate appears to be degraded and/or relatively slowly metabolized, decreasing by only approximately 30% after a 12 h incubation in a Fructose-free medium.
Benjamin S Szwergold - One of the best experts on this subject based on the ideXlab platform.
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Fructose 3 Phosphate production and polyol pathway metabolism in diabetic rat hearts
Metabolism-clinical and Experimental, 1997Co-Authors: Sundeep Lal, Francis Kappler, William C Randall, Truman R. Brown, Anne Taylor, Michael Walker, Benjamin S SzwergoldAbstract:Previous studies have suggested that polyol-pathway and nonenzymatic glycation may be involved in the development of cardiac myopathy, a well-known manifestation of diabetes. Although the exact etiology of this complication is not fully understood, it is likely to be multifactorial. In this study, we investigated the metabolic consequences of diabetes and the effect of aldose reductase inhibitor (ARI) treatment on cardiac tissues of Sprague-Dawley rats. Perchloric acid (PCA) extracts of hearts from the animals were examined using 31P-nuclear magnetic resonance (NMR), gas chromatography/mass spectrometry (GC/MS), and high-performance liquid chromatography (HPLC). In 31P-NMR spectra of diabetic animals, a peak resonating at the chemical shift of 5.8 ppm with a coupling constant of 10 Hz was identified as Fructose-3-Phosphate (F3P). Undetectable in controls (< approximately 20 nmol/g), this metabolite was present at a concentration of 81.3 +/- 16.3 nmol/g wet weight (n = 4) in diabetic rat hearts. GC/MS analysis of these extracts from diabetics also identified a decomposition product of F3P, 3-deoxyglucosone (3DG), at a concentration of 9.4 +/- 3.5 nmol/g (n = 3), compared with 0.98 +/- 0.43 nmol/g (n = 3) in controls. No evidence was found for the expected detoxification products of 3-DG, 3-deoxyFructose and 2-keto 3-deoxygluconate. Concomitant with the elevation of F3P and 3DG, Fructose and sorbitol levels were also elevated in diabetic animals. Surprisingly, ARI treatment was found to have no effect on the levels of these metabolites. These data suggest that either the heart may be unique in its production of Fructose or it may not readily transport the ARI sorbinil. Production of the potent glycating agents F3P and 3DG in diabetics suggests that these compounds may be contributing factors in the glycation of cardiac proteins in the diabetic rat heart.
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identification of galactitol 2 Phosphate and galactitol 3 Phosphate in the lens of galactose fed rats
Metabolism-clinical and Experimental, 1995Co-Authors: Francis Kappler, Bangying Su, Benjamin S Szwergold, William C Randall, Truman R. BrownAbstract:Abstract Production of unusual phosphorylated metabolites in the lens is one of several changes caused by hyperglycemia. Sorbitol 3-Phosphate (Sor-3P) and Fructose 3-Phosphate (Fru-3P) are two such compounds identified in the diabetic lens, and galactitol 2-Phosphate (Gal-2P) and galactitol 3-Phosphate (Gal-3P) are identified here in the galactosemic lens. These new compounds are the first example of galactitol metabolism in mammalian tissue other than liver. Sor-3P and Fru-3P are also present in the galactosemic lens, apparently synthesized directly from their precursors, sorbitol and Fructose, which are elevated in the lens due to increased flux of glucose through the aldose reductase (AR) pathway. The NADPH necessary to support this increased flux is derived from activation of the hexose monoPhosphate shunt (HMPS), which is clearly demonstrated by a large increase in the concentration of sedoheptulose 7-Phosphate (Sed-7P), a HMPS-specific metabolite. Additionally, during 3 weeks of galactose feeding there is a dramatic increase in lenticular concentrations of galactitol, sorbitol, galactose, and Fructose and a sharp decrease in inositol. Glucose remains unchanged. A precipitous loss of both phosphorylated and nonphosphorylated metabolites occurs after 3 weeks, possibly due to lens rupture.
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Metabolism of Fructose-3-Phosphate in the Diabetic Rat Lens
Archives of Biochemistry and Biophysics, 1995Co-Authors: Benjamin S Szwergold, Francis Kappler, William C Randall, Anne H Taylor, Kevin J. Wells-knecht, John W. Baynes, Truman R. BrownAbstract:Abstract Fructose-S-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 μmol/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.
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Production of Fructose and Fructose-3-Phosphate in maturing rat lenses.
Investigative Ophthalmology & Visual Science, 1995Co-Authors: Benjamin S Szwergold, Francis Kappler, William C Randall, Anne H Taylor, Truman R. BrownAbstract:Purpose. A large increase in glycation of crystallins between 1 and 8 months has been demonstrated in lenses obtained from aging rats. The objective of this study was to investigate if an age-associated increase in the levels of any of the phosphorylated and nonphosphorylated sugars in the aging rat lenses could be correlated with this increase. Methods. Lenses were obtained from Sprague-Dawley rats ranging in age from 2 to 20 months. Trichloroacetic extracts of these tissues were analyzed by using 31 P-NMR for sugar Phosphates and high-pressure liquid chromatography equipped with an electrochemical detector for sugars and polyols. Results. Although no elevation in the lenticular glucose levels was observed, an age-associated increase in the concentrations of polyol pathway-associated metabolites-sorbitol, Fructose, sorbitol-3-Phosphate, and Fructose-3-Phosphate-was detected. In contrast, no significant changes were observed in glycolytic or pentose shunt metabolites. Conclusion. Aging lenses accumulate increased concentrations of Fructose and Fructose-3-Phosphate. Because Fructose-3-Phosphate is a potent glycating agent and a potential in vivo source 3-deoxyglucosone, its accumulation in the lens, along with Fructose, may be a contributing factor in the age-associated increase of nonenzymatic glycation in rat lenses
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Fructose metabolism in the human erythrocyte. Phosphorylation to Fructose 3-Phosphate.
Biochemical Journal, 1992Co-Authors: A Petersen, Francis Kappler, Benjamin S Szwergold, Truman R. BrownAbstract:In human erythrocytes, the first step in the metabolism of Fructose is generally thought to be phosphorylation to Fructose 6-Phosphate catalysed by hexokinase. In variance with this assumption, we show here that Fructose in these cells is metabolized primarily to Fructose 3-Phosphate by a specific 3-phosphokinase. This process has an overall estimated Km of 30 mM with respect to extracellular Fructose and an apparent Vmax. of 0.6 mumol/h per ml. At a fixed concentration of Fructose in the medium, the accumulation of Fructose 3-Phosphate was linearly dependent on the duration of incubation up to 5 h and was not affected by glucose. Once accumulated, Fructose 3-Phosphate appears to be degraded and/or relatively slowly metabolized, decreasing by only approximately 30% after a 12 h incubation in a Fructose-free medium.
Francis Kappler - One of the best experts on this subject based on the ideXlab platform.
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Fructose 3 Phosphate production and polyol pathway metabolism in diabetic rat hearts
Metabolism-clinical and Experimental, 1997Co-Authors: Sundeep Lal, Francis Kappler, William C Randall, Truman R. Brown, Anne Taylor, Michael Walker, Benjamin S SzwergoldAbstract:Previous studies have suggested that polyol-pathway and nonenzymatic glycation may be involved in the development of cardiac myopathy, a well-known manifestation of diabetes. Although the exact etiology of this complication is not fully understood, it is likely to be multifactorial. In this study, we investigated the metabolic consequences of diabetes and the effect of aldose reductase inhibitor (ARI) treatment on cardiac tissues of Sprague-Dawley rats. Perchloric acid (PCA) extracts of hearts from the animals were examined using 31P-nuclear magnetic resonance (NMR), gas chromatography/mass spectrometry (GC/MS), and high-performance liquid chromatography (HPLC). In 31P-NMR spectra of diabetic animals, a peak resonating at the chemical shift of 5.8 ppm with a coupling constant of 10 Hz was identified as Fructose-3-Phosphate (F3P). Undetectable in controls (< approximately 20 nmol/g), this metabolite was present at a concentration of 81.3 +/- 16.3 nmol/g wet weight (n = 4) in diabetic rat hearts. GC/MS analysis of these extracts from diabetics also identified a decomposition product of F3P, 3-deoxyglucosone (3DG), at a concentration of 9.4 +/- 3.5 nmol/g (n = 3), compared with 0.98 +/- 0.43 nmol/g (n = 3) in controls. No evidence was found for the expected detoxification products of 3-DG, 3-deoxyFructose and 2-keto 3-deoxygluconate. Concomitant with the elevation of F3P and 3DG, Fructose and sorbitol levels were also elevated in diabetic animals. Surprisingly, ARI treatment was found to have no effect on the levels of these metabolites. These data suggest that either the heart may be unique in its production of Fructose or it may not readily transport the ARI sorbinil. Production of the potent glycating agents F3P and 3DG in diabetics suggests that these compounds may be contributing factors in the glycation of cardiac proteins in the diabetic rat heart.
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identification of galactitol 2 Phosphate and galactitol 3 Phosphate in the lens of galactose fed rats
Metabolism-clinical and Experimental, 1995Co-Authors: Francis Kappler, Bangying Su, Benjamin S Szwergold, William C Randall, Truman R. BrownAbstract:Abstract Production of unusual phosphorylated metabolites in the lens is one of several changes caused by hyperglycemia. Sorbitol 3-Phosphate (Sor-3P) and Fructose 3-Phosphate (Fru-3P) are two such compounds identified in the diabetic lens, and galactitol 2-Phosphate (Gal-2P) and galactitol 3-Phosphate (Gal-3P) are identified here in the galactosemic lens. These new compounds are the first example of galactitol metabolism in mammalian tissue other than liver. Sor-3P and Fru-3P are also present in the galactosemic lens, apparently synthesized directly from their precursors, sorbitol and Fructose, which are elevated in the lens due to increased flux of glucose through the aldose reductase (AR) pathway. The NADPH necessary to support this increased flux is derived from activation of the hexose monoPhosphate shunt (HMPS), which is clearly demonstrated by a large increase in the concentration of sedoheptulose 7-Phosphate (Sed-7P), a HMPS-specific metabolite. Additionally, during 3 weeks of galactose feeding there is a dramatic increase in lenticular concentrations of galactitol, sorbitol, galactose, and Fructose and a sharp decrease in inositol. Glucose remains unchanged. A precipitous loss of both phosphorylated and nonphosphorylated metabolites occurs after 3 weeks, possibly due to lens rupture.
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Metabolism of Fructose-3-Phosphate in the Diabetic Rat Lens
Archives of Biochemistry and Biophysics, 1995Co-Authors: Benjamin S Szwergold, Francis Kappler, William C Randall, Anne H Taylor, Kevin J. Wells-knecht, John W. Baynes, Truman R. BrownAbstract:Abstract Fructose-S-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 μmol/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.
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Production of Fructose and Fructose-3-Phosphate in maturing rat lenses.
Investigative Ophthalmology & Visual Science, 1995Co-Authors: Benjamin S Szwergold, Francis Kappler, William C Randall, Anne H Taylor, Truman R. BrownAbstract:Purpose. A large increase in glycation of crystallins between 1 and 8 months has been demonstrated in lenses obtained from aging rats. The objective of this study was to investigate if an age-associated increase in the levels of any of the phosphorylated and nonphosphorylated sugars in the aging rat lenses could be correlated with this increase. Methods. Lenses were obtained from Sprague-Dawley rats ranging in age from 2 to 20 months. Trichloroacetic extracts of these tissues were analyzed by using 31 P-NMR for sugar Phosphates and high-pressure liquid chromatography equipped with an electrochemical detector for sugars and polyols. Results. Although no elevation in the lenticular glucose levels was observed, an age-associated increase in the concentrations of polyol pathway-associated metabolites-sorbitol, Fructose, sorbitol-3-Phosphate, and Fructose-3-Phosphate-was detected. In contrast, no significant changes were observed in glycolytic or pentose shunt metabolites. Conclusion. Aging lenses accumulate increased concentrations of Fructose and Fructose-3-Phosphate. Because Fructose-3-Phosphate is a potent glycating agent and a potential in vivo source 3-deoxyglucosone, its accumulation in the lens, along with Fructose, may be a contributing factor in the age-associated increase of nonenzymatic glycation in rat lenses
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Fructose metabolism in the human erythrocyte. Phosphorylation to Fructose 3-Phosphate.
Biochemical Journal, 1992Co-Authors: A Petersen, Francis Kappler, Benjamin S Szwergold, Truman R. BrownAbstract:In human erythrocytes, the first step in the metabolism of Fructose is generally thought to be phosphorylation to Fructose 6-Phosphate catalysed by hexokinase. In variance with this assumption, we show here that Fructose in these cells is metabolized primarily to Fructose 3-Phosphate by a specific 3-phosphokinase. This process has an overall estimated Km of 30 mM with respect to extracellular Fructose and an apparent Vmax. of 0.6 mumol/h per ml. At a fixed concentration of Fructose in the medium, the accumulation of Fructose 3-Phosphate was linearly dependent on the duration of incubation up to 5 h and was not affected by glucose. Once accumulated, Fructose 3-Phosphate appears to be degraded and/or relatively slowly metabolized, decreasing by only approximately 30% after a 12 h incubation in a Fructose-free medium.
William C Randall - One of the best experts on this subject based on the ideXlab platform.
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Fructose 3 Phosphate production and polyol pathway metabolism in diabetic rat hearts
Metabolism-clinical and Experimental, 1997Co-Authors: Sundeep Lal, Francis Kappler, William C Randall, Truman R. Brown, Anne Taylor, Michael Walker, Benjamin S SzwergoldAbstract:Previous studies have suggested that polyol-pathway and nonenzymatic glycation may be involved in the development of cardiac myopathy, a well-known manifestation of diabetes. Although the exact etiology of this complication is not fully understood, it is likely to be multifactorial. In this study, we investigated the metabolic consequences of diabetes and the effect of aldose reductase inhibitor (ARI) treatment on cardiac tissues of Sprague-Dawley rats. Perchloric acid (PCA) extracts of hearts from the animals were examined using 31P-nuclear magnetic resonance (NMR), gas chromatography/mass spectrometry (GC/MS), and high-performance liquid chromatography (HPLC). In 31P-NMR spectra of diabetic animals, a peak resonating at the chemical shift of 5.8 ppm with a coupling constant of 10 Hz was identified as Fructose-3-Phosphate (F3P). Undetectable in controls (< approximately 20 nmol/g), this metabolite was present at a concentration of 81.3 +/- 16.3 nmol/g wet weight (n = 4) in diabetic rat hearts. GC/MS analysis of these extracts from diabetics also identified a decomposition product of F3P, 3-deoxyglucosone (3DG), at a concentration of 9.4 +/- 3.5 nmol/g (n = 3), compared with 0.98 +/- 0.43 nmol/g (n = 3) in controls. No evidence was found for the expected detoxification products of 3-DG, 3-deoxyFructose and 2-keto 3-deoxygluconate. Concomitant with the elevation of F3P and 3DG, Fructose and sorbitol levels were also elevated in diabetic animals. Surprisingly, ARI treatment was found to have no effect on the levels of these metabolites. These data suggest that either the heart may be unique in its production of Fructose or it may not readily transport the ARI sorbinil. Production of the potent glycating agents F3P and 3DG in diabetics suggests that these compounds may be contributing factors in the glycation of cardiac proteins in the diabetic rat heart.
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identification of galactitol 2 Phosphate and galactitol 3 Phosphate in the lens of galactose fed rats
Metabolism-clinical and Experimental, 1995Co-Authors: Francis Kappler, Bangying Su, Benjamin S Szwergold, William C Randall, Truman R. BrownAbstract:Abstract Production of unusual phosphorylated metabolites in the lens is one of several changes caused by hyperglycemia. Sorbitol 3-Phosphate (Sor-3P) and Fructose 3-Phosphate (Fru-3P) are two such compounds identified in the diabetic lens, and galactitol 2-Phosphate (Gal-2P) and galactitol 3-Phosphate (Gal-3P) are identified here in the galactosemic lens. These new compounds are the first example of galactitol metabolism in mammalian tissue other than liver. Sor-3P and Fru-3P are also present in the galactosemic lens, apparently synthesized directly from their precursors, sorbitol and Fructose, which are elevated in the lens due to increased flux of glucose through the aldose reductase (AR) pathway. The NADPH necessary to support this increased flux is derived from activation of the hexose monoPhosphate shunt (HMPS), which is clearly demonstrated by a large increase in the concentration of sedoheptulose 7-Phosphate (Sed-7P), a HMPS-specific metabolite. Additionally, during 3 weeks of galactose feeding there is a dramatic increase in lenticular concentrations of galactitol, sorbitol, galactose, and Fructose and a sharp decrease in inositol. Glucose remains unchanged. A precipitous loss of both phosphorylated and nonphosphorylated metabolites occurs after 3 weeks, possibly due to lens rupture.
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Metabolism of Fructose-3-Phosphate in the Diabetic Rat Lens
Archives of Biochemistry and Biophysics, 1995Co-Authors: Benjamin S Szwergold, Francis Kappler, William C Randall, Anne H Taylor, Kevin J. Wells-knecht, John W. Baynes, Truman R. BrownAbstract:Abstract Fructose-S-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 μmol/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.
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Production of Fructose and Fructose-3-Phosphate in maturing rat lenses.
Investigative Ophthalmology & Visual Science, 1995Co-Authors: Benjamin S Szwergold, Francis Kappler, William C Randall, Anne H Taylor, Truman R. BrownAbstract:Purpose. A large increase in glycation of crystallins between 1 and 8 months has been demonstrated in lenses obtained from aging rats. The objective of this study was to investigate if an age-associated increase in the levels of any of the phosphorylated and nonphosphorylated sugars in the aging rat lenses could be correlated with this increase. Methods. Lenses were obtained from Sprague-Dawley rats ranging in age from 2 to 20 months. Trichloroacetic extracts of these tissues were analyzed by using 31 P-NMR for sugar Phosphates and high-pressure liquid chromatography equipped with an electrochemical detector for sugars and polyols. Results. Although no elevation in the lenticular glucose levels was observed, an age-associated increase in the concentrations of polyol pathway-associated metabolites-sorbitol, Fructose, sorbitol-3-Phosphate, and Fructose-3-Phosphate-was detected. In contrast, no significant changes were observed in glycolytic or pentose shunt metabolites. Conclusion. Aging lenses accumulate increased concentrations of Fructose and Fructose-3-Phosphate. Because Fructose-3-Phosphate is a potent glycating agent and a potential in vivo source 3-deoxyglucosone, its accumulation in the lens, along with Fructose, may be a contributing factor in the age-associated increase of nonenzymatic glycation in rat lenses
Anne H Taylor - One of the best experts on this subject based on the ideXlab platform.
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Metabolism of Fructose-3-Phosphate in the Diabetic Rat Lens
Archives of Biochemistry and Biophysics, 1995Co-Authors: Benjamin S Szwergold, Francis Kappler, William C Randall, Anne H Taylor, Kevin J. Wells-knecht, John W. Baynes, Truman R. BrownAbstract:Abstract Fructose-S-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 μmol/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.
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Production of Fructose and Fructose-3-Phosphate in maturing rat lenses.
Investigative Ophthalmology & Visual Science, 1995Co-Authors: Benjamin S Szwergold, Francis Kappler, William C Randall, Anne H Taylor, Truman R. BrownAbstract:Purpose. A large increase in glycation of crystallins between 1 and 8 months has been demonstrated in lenses obtained from aging rats. The objective of this study was to investigate if an age-associated increase in the levels of any of the phosphorylated and nonphosphorylated sugars in the aging rat lenses could be correlated with this increase. Methods. Lenses were obtained from Sprague-Dawley rats ranging in age from 2 to 20 months. Trichloroacetic extracts of these tissues were analyzed by using 31 P-NMR for sugar Phosphates and high-pressure liquid chromatography equipped with an electrochemical detector for sugars and polyols. Results. Although no elevation in the lenticular glucose levels was observed, an age-associated increase in the concentrations of polyol pathway-associated metabolites-sorbitol, Fructose, sorbitol-3-Phosphate, and Fructose-3-Phosphate-was detected. In contrast, no significant changes were observed in glycolytic or pentose shunt metabolites. Conclusion. Aging lenses accumulate increased concentrations of Fructose and Fructose-3-Phosphate. Because Fructose-3-Phosphate is a potent glycating agent and a potential in vivo source 3-deoxyglucosone, its accumulation in the lens, along with Fructose, may be a contributing factor in the age-associated increase of nonenzymatic glycation in rat lenses
