Activators

ACTIVATORS, substances that accelerate an enzymatic reaction. The activation of an enzymatic process can be of two kinds: 1) the addition of one chemical substance or another causes an acceleration of an already proceeding enzymatic reaction; 2) the addition of some specific agent, mainly of organic origin, converts an inactive enzyme into an active form. In accordance with the kind of actions they produce and the nature of their origin, activators are divided into nonspecific and specific. The mechanism of action of nonspecific activators on an enzymatic process can be different: a) the activator acts not on the enzyme itself, but on the substrate, changing it in such a way that it becomes more accessible to the action of the enzyme. In this case, changes of a physical-chemical character can occur, such as: a change in dispersion, precipitation, a change in adsorption properties, surface tension, etc., and changes of a purely chemical character, for example: a change in the degree of dissociation upon a change in pH, etc.; b) the activator acts on the enzyme itself, and this activation of the enzyme can, in turn, proceed in two ways, namely: 1. The activator converts a proenzyme into an enzyme. In these cases, it is very difficult to draw a sharp boundary between specific and nonspecific activators; their action is the same, only the origin of the activator is different. 2. The activator is a protective substance for the enzyme. So-called fermentation activators, according to Haen, are nothing other than a group of anti-enzymes acting on yeast protease and thereby protecting zymase from decomposition by this protease. Nonspecific activators include acids, alkalis, neutral salts, salts of heavy metals, organic compounds, etc.

Recently, through the work of Sørensen, Michaelis, and other authors, the outstanding role of hydrogen ion concentration in enzymatic processes has been precisely established. The activating or, in other cases, inhibitory action that the reaction of the medium exerts in relation to enzymes depends on a whole series of causes. Enzymes are amphoteric electrolytes, and their action depends on the degree of their dissociation, which, in turn, depends on the pH. The formation and decomposition of the intermediate compound of the enzyme with the substrate also depends on the pH. Where the substrate is also an amphoteric electrolyte (proteins), the action of the enzyme depends not only on the ionization of the enzyme but also on the ionization of the substrate. Acids and alkalis in a whole series of chemical processes are true catalysts. Thus, for example, the hydrolysis of proteins, carbohydrates, and fats can be obtained with the help of acids and alkalis. In biochemical processes, acids and alkalis have the significance of activators. Thus, the process of converting pepsinogen into pepsin occurs with the help of HCl. According to Langley, the glands of the stomach produce inactive pepsinogen, which is activated by hydrochloric acid found in gastric juice. Hydrochloric acid can be replaced by other acids. Neutral salts, which activate enzymatic processes, often have a specific action, being in these cases true coenzymes (see), for example: the addition of neutral salts (chlorides, nitrates, sulfates) to amylase inactivated by dialysis regenerates it; tyrosinase is accompanied by an inorganic dialyzing coenzyme, which can be replaced by salts of Zn, Cd, Ca; phosphates are activators for zymase; calcium salts play the role of energetic activators for lipase. Where neutral salts are activators, their optimal concentration lies in the range of 2–5%. Salts of heavy metals in a whole series of cases have the significance of auxiliary catalysts. Amylase and lipase are activated by Mg salts. Of organic compounds, HCN is an activator for papayotin and for urease (Jacobi). For urease, amino acids are also activators. Salts of bile acids activate lipase.

Specific activators include substances of biological origin, most likely of an enzymatic character, which act on a specific enzyme, converting it from a naturally inactive phase (zymogen) into an active enzyme. Activators of this kind are called kinases. An example of this kind of activation is the activation of trypsinogen. Pure pancreatic juice does not act on natural proteins. For its activation, enterokinase, found in intestinal juice, is necessary. Analogous kinases for trypsinogen have been found in bacteria and in snake venom. Regarding the nature of this activation process, there are two opposing opinions. While Bayliss, Starling, and Vernon believe that the activation of trypsinogen is, in turn, an enzymatic process, other authors believe that the formation of a new compound between the proenzyme and the activator takes place here, following stoichiometric laws: a given amount of enterokinase is capable of activating a specific amount of trypsinogen. Another very complex process of proenzyme activation by a kinase is the formation of thrombin. In blood plasma, there is inactive prothrombin, which is activated by a kinase (so-called thrombokinase) contained in blood platelets and in tissue cells. For this activation process, Ca salts are necessary. Activation proceeds according to the following scheme: plasma + thrombogen + thrombokinase -> thrombin. An activator is also pnein (Battelli and Stern), which activates the oxidative processes of main respiration. The mechanism of its action has not yet been clarified.