Formation of Reactive Intermediates from Amadori Compounds under Physiological Conditions

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

“…Such fluorescent changes can be produced by dicarbonyl or glycoxidation products that arise from free sugar, from the initial Schiff bases, and from Amadori and other intermediates (50 -52). Carboxymethyllysine (CmL), a notable AGE, can also arise from a variety of glycoxidation intermediates besides the Amadori product (35,36,53). The acid-stable fluorescent AGE pentosidine (54 -56) can be utilized in principle, but the chemical work-up, protein hydrolysis, and high performance liquid chromatography separation required for each time point makes its use inconvenient for large sets of kinetics.…”

“…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). Hirsch et al (66) found very rapid irreversible formation of 5-and 6-substituted triazines from reaction of aminoguanidine with model dicarbonyls, while Chen and Cerami (68) have reported that reaction of a model Amadori compound with aminoguanidine only leads to formation of triazine and bis-hydrazone products of dicarbonyl fragments derived from the Amadori compound.…”

Age-dependent increase in ortho-tyrosine and methionine sulfoxide in human skin collagen is not accelerated in diabetes. Evidence against a generalized increase in oxidative stress in diabetes.

“…1 A ) were comparable under oxidative and antioxidative conditions, but higher yields of FL were obtained at 3-5 wk under antioxidative conditions. Recent work suggests that these differences result from the more rapid rate of degra-dation of FL to CML and other products under oxidative conditions (24). CML and pentosidine were formed only under oxidative conditions, but at significantly different rates, yielding a CML/pentosidine concentration ratio of ‫ف‬ 50 at 5 wk (Fig.…”

Use of 13C Labeling and NMR Spectroscopy for the Investigation of Degradation Pathways of Amadori Compounds

“…In addition, the HPLC method with UV detection provided only limited information on the decomposition pathways of the sugar moiety. Zyzak et al 15) investigated the degradation fate of another model Amadori compound, N a -formyl-N e -(1-deoxy-D-fructos-1-yl)lysine, at pH 7.4 and 37°C under aerobic conditions. They described the same main degradation pathways as described by Smith and Thornalley, namely, formation of carboxymethyl-lysine (CML) by oxidative degradation and liberation of lysine by reversal of the Amadori rearrangement.…”

“…Although various types of 13 C-labeled glucose are commercially available, and different information is obtained depending upon the labeled position, [1-13 C]glucose was used here because this position is contained in most degradation products reported to date. 6,7,14,15) [ 13 C]DHL (see Chart 1) was synthesized by a direct condensation of glucose and HL, as in the synthesis of unlabeled DHL, 20) purified by TLC followed by solid-phase extraction, and characterized by 1 H-NMR spectroscopy and COSY. The 1 H-NMR spectrum in deuterium oxide was similar to the reported spectrum of unlabeled DHL in phosphate buffer (pH 7.4), 20) except the H1 resonance of the fructose moiety (Fru) was split by 13 C incorporation into the C1 position, as shown in Fig.…”