**2. Biochemical basis of AGEs**

Protein glycation can be subdivided into three major stages: early, middle, and late. In the initial reaction, the carbonyl group (C=O) of a reducing sugar, such as glucose, reacts with the amino group (NH2) of the amino acid residue in the protein

#### *Advanced Glycation End Products and Oxidative Stress in a Hyperglycaemic Environment DOI: http://dx.doi.org/10.5772/intechopen.97234*

to form a Schiff base (C=N). This Schiff base is relatively unstable and eventually becomes an enol, causing Amadori rearrangement and finally leading to the formation of a stable Amadori compound (C-N).

Kunkel found abnormal haemoglobin levels in the blood of normal people [16], and increased levels of abnormal haemoglobin were observed in patients with diabetes [17]. Currently, haemoglobin A1c (HbA1c), which is used as a diagnostic criterion for diabetes, is formed via Amadori rearrangement of the amino-terminal valine of the haemoglobin β chain and reflects the blood glucose level for 3–4 weeks [18, 19]. In the intermediate stage, α-dicarbonyl compounds, which are derivatives of sugars such as glucosone, 3-deoxyglucosone, glyoxal, and methylglyoxal, are produced from Amadori compounds. After further reacting with the amino compound, these α-dicarbonyl compounds undergo dehydration, condensation, cyclisation, and intermolecular crosslinking to form stable AGEs in the advanced stage (**Figure 2**). The pathway through which AGEs are produced from these series of Schiff bases via Amadori compounds and α-dicarbonyl compounds is known as the Hodge pathway [4]. In addition, the Namiki pathway, which produces glyoxal and glycolaldehyde, generates free radicals from Schiff bases without producing Amadori compounds [20].

Because the Schiff base is in a state in which it easily undergoes a secondary reaction with sugars and amino acids, dehydration, isomerisation, cleavage, cyclisation, and polymerisation can be repeated; the final products produced through these intermediates are extremely diverse. Therefore, the structures of many compounds are complicated, and most have not been identified. The structures of typical AGEs, such as CML, pyrarin, argpyrimidine, and pentosidine, have been reported (**Figure 2**).

#### **Figure 2.**

*The main chemical structures of AGEs. Abbreviations used: CML, Nε-carboxymethyl-lysine; CEL, Nε-(1 carboxyethyl)lysine; CML, Nω-(Carboxymethyl)-L-arginine; G-H1, Nδ-(5-hydro-4-imidazolon- 2-yl) ornithine; MG-H1, Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine; 3DG-H1, Nδ-[5-(2,3,4 trihydroxybutyl)-5-hydro-4-imidazolon-2-yl] ornithine; GA- pyridine, Glycolaldehyde-pyridine; FTP, Formyl Threosyl Pyrrole; GLAP, glyceraldehyde-derived pyridinium-type advanced glycation end product; GOLD, glyoxal-derived lysine dimer; MOLD, methylglyoxal-derived lysine dimer; DOLD, 3-deoxyglucosone-derived lysine dimer*
