The Heat Coagulation of Human Serum Albumin

The present studies were designed to develop a rapid micromethod for investigation of the effects of heat on relatively concentrated solutions of human serum albumin. The method so devised is proposed for the routine study of commercial preparations, and for inquiry into some of the factors that appear to determine the thermal stability of an albumin solution. As will be clear from the paragraphs that follow, we are using the word stability in a very restricted sense: the studies pertain only to the formation of coagula or aggregates of presumably denatured albumin that are capable of producing a considerable Tyndall effect. The observed phenomenon, which will be referred to as cloud formation, is, according to the views of various authorities (l-lo), the net result of two consecutive reactions: the denaturation or unfolding of the protein molecules in solution, and the flocculation, aggregation, or polymerization of the unfolded molecules to form particles that are large enough and present in sufficient concentration to scatter light and give the appearace of a cloud or turbidity. The factors that influence the rate of formation of soluble denatured protein at higher temperatures are not considered in the present study, although work is in progress on a method to ascertain the state of the protein in solution. Likewise, the formation of soluble cleavage products that might arise from thermal degradation under special conditions is not considered.