Glucose protein glycation

Hb A,c and fructosamine are measures of protein glycation and serve as indices of long-term glucose conirol. 

FIGURE 1. Protein glycation. The open chain form of glucose can react with protein reversibly, forming a Schiff base. This may then rearrange to form the Amadori product, which in turn can form advanced glycation end products (AGE). The formation of AGE, attached or unattached to protein, occurs in a transition metal-dependent oxidative process. This process has also been termed glycoxidation. 

Ascorbic acid s ability to compete with glucose during protein glycation in vitro and also apparently in vivo requires further comment (Stolba et al., 1987 Davie et al., 1992). Like many reducing sugars ascorbic acid can generate oxidants in the presence of transition metals, in much the same way as glucose. Indeed, any... 

As shown in Figure 10.15, glucose can react non-enzymically with free amino groups on proteins, resulting in glycation of the proteins. Glycated proteins include ... 

Amadori-type early glycosylation products (Brownlee et /., 1988). Protein that has been glycated in vitro is con-formationally altered. For example, the amount of early glycosylation products in vivo in diabetics, whether on haemoglobin (Hb) or basement membrane, increases when blood glucose levels are normalized by treatment. 

Hunt, J.V., Dean, R.T. and Wolff, S. (1988). Hydroxyl radical production and autoxidative glycosylation. Glucose oxidation as the cause of protein damage in the experimental glycation model of diabetes mellitus and ageing. Biochem. J. 256, 205-212. 

Hunt, J., Bottoms, M. and Mitchinson, M.J. (1993). Oxidative alterations in the experimental glycation model of diabetes mellitus are due to protein-glucose adduct oxidation. Biochem. J. 291, 529-535. 

Glucose may auto-oxidize (like other alphahydroxy-aldehydes) and generate hydroxyl radicals in a transition-metal-catalysed reaction, and induce both fragmentation and conformational changes in glycated proteins (Hunt et al., 1990). 

Watkins NG, Thorpe SR, Baynes JW. Glycation of amino groups in protein. Studies on the specificity of modification of RNase by glucose. J. Biol. Chem. 1985 260 10629-10636. 

Several markers for the Maillard reaction have been described in the literature. For example, the product initially formed between glucose and lysine is partly transformed into furosine (Heyns et ah, 1968) on acid hydrolysis. Conversely, the fluorescent amino acid pentosidine (Sell and Monnier, 1989) is an advanced glycation endproduct (AGE) and may form covalent bonds between proteins (cross-linking). Furthermore, the Maillard reaction leads to an increase in characteristic fluorescence (excitation 370 nm, emission 440 nm) (Monnier et ah, 1984 Pongor et ah, 1984). 

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