Human Serum Albumin - Glycosylation

Glycosylation

It has been known for a long time that human blood proteins like hemoglobin and serum albumin may undergo a slow non-enzymatic glycation, mainly by formation of a Schiff base between ε-amino groups of lysine (and sometimes arginine) residues and glucose molecules in blood (Maillard reaction). This reaction can be inhibited in the presence of antioxidant agents. Although this reaction may happen normally, elevated glycoalbumin is observed in diabetes mellitus.

Glycation has the potential to alter the biological structure and function of the serum albumin protein.

Moreover, the glycation can result in the formation of Advanced Glycosylation End-Products (AGE), which result in abnormal biological effects. Accumulation of AGEs leads to tissue damage via alteration of the structures and functions of tissue proteins, stimulation of cellular responses, through receptors specific for AGE-proteins, and generation of reactive oxygen intermediates. AGEs also react with DNA, thus causing mutations and DNA transposition. Thermal processing of proteins and carbohydrates brings major changes in allergenicity. AGEs are antigenic and represent many of the important neoantigens found in cooked or stored foods. They also interfere with the normal product of nitric oxide in cells.

Although there are several lysine and arginine residues in the serum albumin structure, very few of them can take part in the glycation reaction. It is not clear exactly why only these residues are glycated in serum albumin, but it is suggested that non-covalent binding of glucose to serum albumin prior to the covalent bond formation might be the reason.