A theory of the mechanism of enzyme action.

Abstract

A LTHOUGH there exists an extensive literature concerned with the nature of enzyme action and the chemistry and structure of enzymes, little progress has been made toward understanding the mechanism of enzyme action in explicit terms of the molecular structure of proteins, prosthetic groups, and their combinations. Woolf (1931), Szent-Gyorgyi (1941, 1947), and LuValle and Goddard (1948) are among those who have dealt with the problem and have proposed mechanisms, but while they have treated in detail certain of the fundamental aspects of enzyme action, they have given only cursory consideration to the structure and role of the protein components of enzymes. There can be little doubt that the protein portion of the enzyme molecule plays an essential role in its reactions. Indeed, many enzymes consist, so far as is known, entirely of protein. Enough is known at the present time of the structure of enzymes, of the nature of enzymatic reactions, and of the kinds of substrates and products involved in enzymatic processes to justify the attempt to evolve a general hypothesis of the mechanism of these reactions. Except for the participation of inorganic ions, it is evident that enzymes are primarily organic compounds and that, in the majority of cases, they act upon organic substances, the reactions involving for the most part organic oxidations, reductions, hydrolyses, and condensations. In the present treatment the approach will be made from the following point of view: that reactions involving organic substances can be examined from the standpoint of present-day concepts of the nature and mechanisms of organic reactions. It will be shown in this paper that it is possible to consider all enzyme reactions to involve the same fundamental property of the protein molecule, and that when prosthetic groups are essential participants in the process, as in oxidation-reduction reactions, the role of the prosthetic group is auxiliary and not an independent one. In short, it is suggested that enzyme reactions of all kinds have as a common denominator a unique and characteristic property of the protein molecule, which lies in its possession of a long hydrogenbridged system of peptide linkages. The question of the mechanism of enzyme action is essentially one of the means by which the enzyme brings about a sufficient lowering of the activation energy of a normally slow chemical reaction to cause its rate to be enormously increased over what it would be under non-enzymatic conditions and at comparable conditions of pH and temperature (see Kalckar, 1946).