The reaction of 3-deoxy-d-glycero-pentos-2-ulose (“3-deoxyxylosone”) with aminoguanidine

Hirsch, Ján; Bayness, John W.; Blackledge, James A.; Feather, Milton S.

doi:10.1016/0008-6215(91)80024-h

Cited by 14 publications

(3 citation statements)

References 10 publications

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“…In animal models of diabetes, AG also prevents development of complications, including nephropathy (Soulis-Liparota et al, 1991;Itakura et al, 1991), retinopathy (Hammes et al, 1991), neuropathy (Kihara et al, 1991;Cameron et al, 1992;Yagihashi et al, 1992), and vascular disease (Kihara et al, 1991;Corbett et al, 1993). One hypothesis to explain AG inhibition of advanced stages of the Maillard reaction is its reaction with a-dicarbonyl compounds formed by oxidative (e.g., glyoxal) and nonoxidative (e.g., 3-deoxyglucosone) mechanisms, to form stable aminotriazine derivatives (Neunhoeffer, 1984;Hirsch et al, 1991). We have detected 3-amino-1,2,4-triazine as a major product formed during autoxidation of glucose in the presence of AG (unpublished), consistent with the proposed role of glyoxal as a key intermediate in autoxidative glycosylation of protein during the Maillard reaction in vitro.…”

Section: Discussionmentioning

confidence: 99%

Identification of Glyoxal and Arabinose as Intermediates in the Autoxidative Modification of Proteins by Glucose

Wells‐Knecht

Zyzak²,

Litchfield³

et al. 1995

Biochemistry

574

354

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Glycation and oxidation reactions contribute to protein modification in aging and diabetes. Formation of dicarbonyl sugars during autoxidation of glucose is the hypothetical first step in the autoxidative glycosylation and subsequent browning of proteins by glucose [Wolff, S. P., & Dean, R. T. (1987) Biochem. J. 245, 243-250]. In order to identify the dicarbonyl sugar(s) formed during autoxidation of glucose under physiological conditions, glucose was incubated in phosphate buffer (pH 7.4) at 37 degrees C under air (oxidative conditions) or nitrogen with transition metal chelators (antioxidative conditions). Dicarbonyl compounds were analyzed spectrophotometrically and by HPLC after reaction with Girard-T reagent. Carbohydrates were analyzed by gas chromatography-mass spectrometry. Both dicarbonyl sugar and arabinose concentrations increased with time and glucose concentration in incubations conducted under oxidative conditions; only trace amounts of these products were detected in glucose incubated under antioxidative conditions. HPLC analysis of adducts formed with Girard-T reagent indicated that glyoxal was the only alpha-dicarbonyl sugar formed on autoxidation of glucose. Glyoxal and arabinose accounted for > or = 50% of the glucose lost during a 21 day incubation. Neither glucosone nor its degradation product, ribulose, was detectable. Reaction of glyoxal with RNase yielded the glycoxidation product, N epsilon-(carboxymethyl)lysine, while arabinose is a source of pentosidine. Our results implicate glyoxal and arabinose as intermediates in the browning and crosslinking of proteins by glucose under oxidative conditions. They also provide a mechanism by which antioxidants and dicarbonyl trapping reagents, such as aminoguanidine, limit glycoxidation reactions and support further evaluation of these types of compounds for inhibition of chemical modification and crosslinking of proteins during aging and diabetes.

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Section: Discussionmentioning

confidence: 99%

Identification of Glyoxal and Arabinose as Intermediates in the Autoxidative Modification of Proteins by Glucose

Wells‐Knecht

Zyzak²,

Litchfield³

et al. 1995

Biochemistry

574

354

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“…Instead, aminoguanidine, through its guanidinium functionality, was found to inhibit another AGE formation pathway by scavenging reactive dicarbonyl intermediates (Scheme 1) that arise from glycoxidation during glycation (65)(66)(67)(68). Dicarbonyls can include glyoxal and glycoaldehyde that arise from free sugar or from Schiff bases (via the Namiki pathway) and "glucosones" (deoxydiketoses or deoxyaldoketoses) which can arise from Amadori intermediates (35,36,38,53).…”

Section: Discussionmentioning

confidence: 99%

In Vitro Kinetic Studies of Formation of Antigenic Advanced Glycation End Products (AGEs)

Booth

Khalifah

Todd

et al. 1997

Journal of Biological Chemistry

263

194

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“…Chelation of metal ions that act as catalysts in the oxidative reactions and scavenging of free radicals by antioxidants are some of the suggested mechanisms (9). On the other hand, AG has been suggested to act by trapping the dicarbonyl intermediate (40,(42)(43)(44) and hence at a stage distal to the oxidative reaction (9). In the in vitro AGE-BSA collagen cross-linking inhibition assay (31), the inhibition of cross-linking by AG, ALT 462, and ALT 486 is measured post-AGE-formation.…”

Section: Age-formation and Cross-linking Inhibitory Activity Of Alt 4mentioning

confidence: 99%

Chronic Dosing With Aminoguanidine and Novel Advanced Glycosylation End Product-Formation Inhibitors Ameliorates Cross-Linking of Tail Tendon Collagen in STZ-Induced Diabetic Rats

Kochakian¹,

Manjula²,

Egan³

1996

Diabetes

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Solubility of tail tendon collagen from normal, streptozotocin-induced diabetic Lewis rats, and diabetic animals treated with aminoguanidine and two novel advanced glycosylation end products (AGE)-formation inhibitors was investigated by limited pepsin digestion under acidic conditions. Assays were conducted using tail tendon collagen from Lewis rats obtained from two different vendors, Harlan and Charles River Laboratories. Collagen solubility was assessed by following the kinetics of pepsin digestion. The data revealed that the rate of digestion for diabetic animals is markedly slow relative to that of normals. More strikingly, the kinetics of the diabetic animals showed the feature of a lag in digestion regardless of the animal source. Experiments designed to optimize the difference in solubility between normal and diabetic animals demonstrated that Charles River animals exhibit a greater window of solubility than the Harlan animals. More importantly, a pronounced effect of aminoguanidine, an AGE-formation inhibitor, was observed in Charles River animals, but not in the Harlan animals, presumably because of the larger window of solubility between the normal and the diabetic animals in the former. These data indicated that the Charles River Lewis rats are an animal model that demonstrates greater efficacy in this assay. Analysis of in vivo screens designed to test efficacy of aminoguanidine and two novel AGE-formation inhibitors, ALT 462 and ALT 486, demonstrated that monitoring an in vivo dose response is highly dependent on the enzyme concentration as well as the time of digestion, and that 1.5 h of digestion and 10 microg/ml pepsin (5 pg pepsin/mg collagen) appeared optimal. Under these conditions, a 29% normalization of solubility was observed with aminoguanidine at 100 mg/kg body wt, whereas a similar normalization was observed at 10 mg/kg body wt for both ALT 462 and ALT 486. Thus, on a molar basis, ALT 462 and ALT 486 are at least 20 times more potent than aminoguanidine. This is the first demonstration of dose-dependent efficacy for AGE-formation inhibitors in animal models, and as such, this assay provides a method with which to assess the in vivo efficacy of other such inhibitors.

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The reaction of 3-deoxy-d-glycero-pentos-2-ulose (“3-deoxyxylosone”) with aminoguanidine

Cited by 14 publications

References 10 publications

Identification of Glyoxal and Arabinose as Intermediates in the Autoxidative Modification of Proteins by Glucose

Identification of Glyoxal and Arabinose as Intermediates in the Autoxidative Modification of Proteins by Glucose

In Vitro Kinetic Studies of Formation of Antigenic Advanced Glycation End Products (AGEs)

Chronic Dosing With Aminoguanidine and Novel Advanced Glycosylation End Product-Formation Inhibitors Ameliorates Cross-Linking of Tail Tendon Collagen in STZ-Induced Diabetic Rats

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