Pentosidine formation

Although AG inhibited pentosidine formation at concentrations higher than 18 mM, Urios et al.5S9 found that, at 1.6-18 mM, pentosidine formation was enhanced in Type I insoluble collagen (9 mg rnL 200 mM phosphate buffer, pH 7.4,250 mM glucose, 28 d, 37 °C). The formation of pentosidine was increased maximally at 8 mM (roughly doubled), but almost completely inhibited at 89 mM. 

P. Chellan and R. H. Nagaraj, Early glycation products produce pentosidine cross-links on native proteins Novel mechanism of pentosidine formation and propagation of glycation, J. Biol. Chem., 2001, 276, 3895-3903. 

Sell, D. R., Lapolla, A., Odetti, P., Fogarty, J., and Monnier, V. M., Pentosidine formation in skin correlates with severity of complications in individuals with long-standing IDDM. Diabetes 41, 1286-1292 (1992). 

The 328/378- and 370/440 fluorescences are characteristic for pentosidine and Maillard products, respectively (Dyer et al., 1991b) while the 317/407 fluorescence indicates dityrosine formation (Huggins et al., 1993). 

The increase of carboxymethyllysine (batch 1) and pentosidine (batches 1 and 11) thus observed provided additional proof for fhe Maillard reaction in caries (fable 3, figs. 2, 3). The pentosidine level ranged from abouf equal fo a manifold of the level in sound dentin. The formation of pentosidine can only account for a fraction of the increase in 328/378 fluorescence, which is in accordance with a major contribution from a different fluorophore as stated above. Unfortunately, an increase of dify-rosine as expected from fhe gain in 317/407 fluorescence (fable 2) could not be substantiated unequivocally by HPLC analysis because dityrosine co-eluted with lysylpyridinoline. Even if we would consider dityrosine to originate the lysylpyridinoline peaks observed in HPLC of carious dentin, but not of sound dentin, only one quarter of the increase in 317/407 fluorescence would derive from difyrosine. 

Dyer DG, Blackledge JA, Thorpe SR and Baynes JW (1991b) Formation of pento-sidine during nonenzymatic browning of proteins by glucose identification of glucose and other carbohydrates as possible precursors of pentosidine in vivo. J Biol Ghem 266,11654-11660. 

Plasma levels of creatine as well as of pentosidine increase in diabetic nephropathy, which leads to the possibility of creatine replacing arginine in the formation of pentosidine.376 Accordingly, lysine was incubated at 60 °C for 48 h with ribose and creatine, when on HPLC a novel fluorescent peak was detected. It reacted with an anti-pentosidine antibody and was identified by NMR and FAB-MS as C-pentosidine. 

Scheme 8.3 Pathway for the formation of lysine-arginine crosslinks, glucosepan, pentosi-nane, pentosidine, DOPDIC, and DOGPIC115 377...

The browning of proteins by glucose is catalysed by transition metal ions and by air. The AGEs in tissue proteins best characterised are CML and pentosidine, products of a combination of glycation and oxidation of hexoses or ascorbate. In view of facts such as these, the AGE hypothesis evolved to accommodate a role for oxidative stress.399 Multiple autoxidative mechanisms are involved in the formation of AGEs, as illustrated in Scheme 8.4 for the formation of CML from glucose, including ... 

Oxidative browning in vitro can be distinguished from nonoxidative browning by the formation of CML. Although ribose and 3-DG brown proteins at essentially the same rate under both types of system, CML is formed only under oxidative conditions.20,51 This requirement for oxygen in the formation of CML and pentosidine should be considered to be a good approximation, rather than absolute. These AGEs could... 

AGE formation is related to hyperglycaemia in diabetes, but not in uraemia, because AGE levels do not differ between diabetic and nondiabetic haemodialysis patients, which is a mystery.435 Pentosidine and CML were elevated in uraemic plasma and then-levels were not correlated with fructoselysine levels. The addition of aminoguanidine and OPB-9195 lowered the yield of AGEs in both uraemic and control plasma. Carbonyl stress was therefore thought to be a contributory factor in uraemia. 

Inhibition of the formation of CML and pentosidine from various AGE precursors and BSA was more efficient with OPB-9195 than with AG.601 OPB-9195 also inhibited the formation of two ALEs (malondialdehyde-lysine and 4-hydroxynonenal-protein adduct) with an efficiency similar to that of AG. In glucose-based peritoneal dialysis fluid, OPB-9195 inhibited AGE formation, probably by trapping reactive carbonyls, such as GO, MGO, and 3-deoxyglucosone. 

K. Miyazaki, R. Nagai, and S. Horiuchi, Formation of pentosidine-like AGE structure from creatine, in G, 2002, 457-458. 

G20. Grandhee, S. K., and Monnier, V. M., Mechanism of formation of the Maillard protein cross-link pentosidine. Glucose, fructose, and ascorbate as pentosidine precursors. J. Biol. Chem. 266, 11649-11653 (1991). 

D. G. Dyer, J. K. Blackledge, S. R. Thorpe, and J. W. Baynes Formation of pentosidine during nonenzymatic browning of proteins by glucose. Journal of Biological Chemistry ll, 11654 (1991). 

K. M. Biemel, O. Reihl, J. Conrad, and M. O. Lederer, Formation pathways for lysine-arginine cross-Unks derived fi om hexoses and pentoses by Maillard processes. Unraveling the structure of a pentosidine precursor, /. Biol. Chem., 276 (2001) 23405-23412. 

Apart from the modification of amino acid side chains in individual protein strands, cross-linkage of two protein chains can also occur. Some of the structures are shown in Formula 4.100. Pentosidine was first found in physiological protein. It strongly fluoresces and is formed by bridging an arginine residue with a lysine residue via a pentose. The concentrations of pentosidine in food are comparatively low (Table 4.16). The formation of pentosidine is assumed to be as shown in Formula 4.101. Formation of the Amadori product with the 8-amino group of lysine is followed by water elimination at C-2 and C-3 of pentose with the formation of the 4,5-diulose, which condenses with the... 

The second method of melanoidin formation, which also leads to protein oligomers, is more typical for foods. This reaction assumes covalent bond formation of transformation products of sugars on the side chains of proteins, especially of bound lysine, arginine or cysteine, to form chromophore structures. Some of the previously mentioned AGE structures, such as pentosidine (4-241) are coloured. Other chromophores include substances that are formed in systems containing furan-2-carbaldehyde. The lysyl residue in a peptide chain reacts in a neutral solution with furan-2-carbaldehyde, forming chromophore (4-253). Also described are... 

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