Biological inactivation of proteins by the Maillard reaction. Effect of mild heat on the tertiary structure of insulin.

The effects of the Maillard reaction on the biological activity of insulin as a hormone, and on the utilization of egg albumin as a source of amino acids have been studied. In order to know the number, the position, and the effect of the glucose residues that bind a protein, crystalline zinc insulin was stored with 14C-glucose at 37° and 68% R.H. for four months. The unreacted sugar was separated from insulin in a Bio-Gel column and the bound radioactivity counted. The first sugar residue reacted within five days, and additional 2.7 residues reacted through the end of the storage. Binding of 1.4 residues increased the a~id solubility of insulin ten times suggesting impairment of hexamer formation. The ability of this Maillard insulin in controlling the blood glucose and tryptophan levels suffered little or no change. After four months the s9lubility decreased by a factor of