Coenzymes

COENZYMES, specific activators that form a necessary constituent part of the active system of certain enzymes. Coenzymes do not represent a fundamental difference from kinases, and the application of one designation or the other is determined in essence by the practice established for the given case. For more details on the place of coenzymes in the series of other activating substances, see Activators. The inactive part of the enzyme system remaining after the separation of the coenzyme is called an apoenzyme; the addition of the coenzyme again brings the apoenzyme into an active state (example: cozymase + apozymase = active zymase). In many cases, the role of coenzymes is played by simple, precisely known chemical compounds; thus, the coenzyme of the plant protease, papayotin, is hydrocyanic acid, HCN. - Cozymase. In the action of all plant, bacterial, and animal zymases (see), i.e., enzyme systems of alcoholic, lactic acid, and other types of fermentation, as well as glycolysis, a special coenzyme takes part, the so-called cozymase. The latter is an easily dialyzable, thermostable substance, apparently close in its chemical nature to nucleic acids, more precisely to nucleotides (Euler). Yeast and muscles are especially rich in it. After dialysis or washing with water, yeast and muscle tissue contain only inactive apozymase; the latter can be reactivated by adding cozymase in the form of a dialysate of the corresponding cells or an extract from them, in which the apozymase has been destroyed by boiling. Cozymases of various cells (yeast, muscles, erythrocytes, bacteria) are identical in their action and probably also in their chemical nature; in any case, they can mutually replace each other; washed yeast is activated by the cozymase of muscles or lactic acid bacteria and vice versa (Meyerhof, Euler). Cozymase is also identical with the coenzyme of cellular respiration ("pnein" of Battelli-Stern, "Atmungskörper" of Meyerhof). This is quite natural, since the first phases of the oxidative breakdown of carbohydrates, which represent the most important substrate of tissue respiration, coincide with the same phases of fermentation. The mechanism of action of cozymase has not yet been fully established. One of the first stages of sugar fermentation is the formation of esters with phosphoric acid (see Hexosephosphoric acids, Harden-Young equation). Without cozymase, the initial rearrangement of the sugar molecule necessary for this phosphorylation is impossible (Euler, Neuberg, Bodnar). Likewise, in the absence of cozymase, aldehydemutases (see Cannizzaro reaction) do not act, producing the conversion of the most important intermediate product of carbohydrate breakdown—methylglyoxal—into pyruvic or lactic acid. In the absence of cozymase, the fermentation of hexose phosphate stops at the methylglyoxal stage (Neuberg, Kobel). Thus, cozymase plays the role of cophosphatase (activator of the phosphorylating enzyme) and comutase (coenzyme of aldehydemutases) during fermentation. The remaining phases of fermentation—the breakdown of hexose phosphate to methylglyoxal and the splitting of pyruvic acid by carboxylase (see) into acetaldehyde and CO₂—apparently do not require the participation of cozymase, i.e., they can be carried out with the help of apozymase alone. Whether the participation of cozymase is necessary in the Cannizzaro reaction, which converts acetaldehyde into alcohol, has not yet been established.