Thermal coagulation of serum proteins; the effects of iodoacetate, iodoacetamide, and thiol compounds on coagulation.

In the course of studies of the effect of heat on the proteins of human serum it was observed that, at pH 7.4, minute amounts of sodium iodoacetate completely prevented thermal coagulation, while traces of mercaptans markedly enhanced the coagulation. The present paper is an analysis of these observations. The thermal coagulation of a protein, such as egg albumin, has been postulated (1) to consist of two processes, the denaturation reaction between the protein and hot water, followed by the agglutination of the altered protein in particulate form. From x-ray diffraction studies (2) it has been demonstrated that denaturation of proteins involves liberation or generation of peptide chains which aggregate on coagulation into parallel bundles. This over-all physical change is affected by many factors including pH (3, 4) and the concentration (5) and nature (6, 7) of electrolytes in the solution. A number of substances prevent thermal coagulation of proteins, such as concentrated thiocyanate and iodide (6), germanin (S), certain sugars in concentrated solution (9, lo), thymus nucleate (ll), and certain fatty acids and detergents (12, 13). However, the only agents which inhibit coagulation in the low concentration range in which iodoacetate is active are detergents and thymus nucleate, and the inhibitory effect of the latter substance, unlike that of iodoacetate, is abolished by relatively low concentrations of sodium chloride (11). Because of implications in pathology (14) most of the experiments described in this paper were carried out with normal human serum in order to secure data on this intact system. However, the principal effects were also observed when solutions of crystallized bovine plasma albumin, crystallized egg albumin, and human serum albumin were employed; preliminary experiments with these simpler systems, which bear on the mechanism of the phenomenon, are included.