# Popular Science Monthly/Volume 73/July 1908/A Physiological Problem: Enzymes

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* A PHYSIOLOGICAL PROBLEM: ENZYMES
By ORVILLE HARRY BROWN, Ph.D., M.D.
PHYSICIAN IN CHIEF OF THE MISSOURI STATE SANATORIUM FOR INCIPIENT TUBERCULOSIS
MT. VERNON, MO.
THE question of enzymes is one of fascinating interest to the biologist. There is more or less of a mystical atmosphere surrounding these unknown ever-present bodies in all living organisms, on account of the difficulty in effecting their isolation, and in regard to the method in which they perform their function. The study of enzymes has been pursued with much vigor for years by eminent investigators of the biological sciences, and yet their exact nature is almost as little understood to-day as ever. No enzyme has been absolutely isolated, and consequently the chemical constitution of these principles is yet a matter of conjecture. We can, however, unerringly detect their presence, both qualitatively and quantitatively.
The terms enzyme and ferment as used to-day are practically synonymous. The latter term is doubtless the more familiar of the two to the laity. A classical example of fermentation is the changing of sugar, by means of yeast, to alcohol and carbonic acid gas. The yeast is necessary to this process, in so far as it elaborates the active agent—enzyme, or ferment—which is essential. The yeast, more properly according to our former conception, than now, is spoken of as an organized ferment. This was on account of the supposition that the yeast itself was the ferment. It has only recently been shown that a substance can be extracted from the yeast cell, which brings about the process, spoken of as fermentation. In contradistinction to the organized ferments there were the unorganized ferments, as, for example, the enzymes of the alimentary canal, which were capable of bringing about digestion as w T ell outside of the body in a test beaker, as in their normal habitat, the stomach and intestines. The separation of a material from the yeast cell, which still possessed its activity made obsolete the classification of unorganized and organized ferments. The agents which were formerly classified under the two heads, although differing in characteristics, are alike in that both are definite chemical substances secreted or manufactured by cells—a single-celled organism in one case and a multicellular in the other. Many bacteria were formerly believed to belong to the same class as the yeast, and thought to possess a fermentative function; now it is known that the bacteria elaborate a substance which has the enzymotic properties.
The physiologist defines an enzyme as a body, which, remaining ​unaltered itself, accelerates a chemical reaction, otherwise going on very slowly. To elucidate with an example: fat is a chemical union of two compounds, one of which is called a fatty acid, and the other an alcohol. Fat, in the absence of a fat splitting enzyme, yields very small quantities of these two substances in the course of a long time. But, in the presence of a proper enzyme the fat yields considerable quantities of fatty acid and alcohol in a comparatively short time. The rapidity of the splitting is directly proportional to the amount of the enzyme added. A small amount of the enzyme will decompose just as much of the fat as a large quantity will, but a longer period of time is required. A quantity of the enzyme may be used over and over again for splitting any amount of fat, unless it is destroyed by bacteria, heat, chemicals, or some other deleterious agent.
When fat and an enzyme are placed in a test tube together, not all the fat is changed into its component parts. The reaction proceeds until more than half the fat is decomposed. Then there is a reversal of the chemical reaction. Fat is reformed from the fatty acid and alcohol; the splitting process proceeds very slowly if at all. The fat formation goes on as the predominant process in the tube until an excess of fat is formed, when a reversal again occurs, and fat decomposition becomes the chief reaction in the test tube. The alternate breaking down and building up goes on indefinitely, like the swinging back and forth of a pendulum. The sweep of the pendulum when first started may be broad, but if allowed to swing uninterruptedly, there is a gradual diminution of the distance traversed until the pendulum eventually comes to a standstill. Thus it is with the chemical reaction. This power of an enzyme to carry a chemical reaction in either direction is spoken of as the reversibility of enzymes. This has not been demonstrated to be true of all these bodies, but the physiologist delights in the speculation that it is; and many are the problems planned to demonstrate this characteristic in this or that enzyme.
Enzymes have important functions to perform in both animal and plant economy. Practically all of the chemical reactions, normally occurring in life processes, are believed to be aided by ferments. The distribution of these bodies in an organism is general. In man they are found, not only in the alimentary canal, but in the blood and lymph and presumably every cell of the body. The ferments of the alimentary canal are there for the purpose of splitting the food stuffs into their components, which are more readily absorbable than the original materials. Those of the liquids and cells of the body reform and build up the food elements into the vital tissues or protoplasm of the organism.
Another process in which enzymes play an omnipotent part is that of respiration. The oxidation of the protoplasmic constituents, from ​which the heat and energy originate, and upon which life is so alarmingly dependent—going on, not chiefly in the lungs or blood, but in every cell of the body, is responsible to an enzyme, or catalase, known as an oxidase. The result of these elements, which is the bringing about of the union of oxygen with the tissue, is perfectly well known, but the chemical nature and the physical characteristics of the oxidases, are problems for speculation.
The enzymes in plant cells are similar at least in action to the corresponding ones of animals; but, in addition to those possessed by animals, plants have ferments which enable them, in the sunlight, to use carbonic acid gas in building up some of its cell constituents.
The method used in the laboratory for demonstrating the presence of an enzyme is very simple. The tissue to be examined is finely minced and ground up in a mortar. In order to facilitate the division of the cells, sand may be used in the grinding. The pulverized mass is then mixed with water or a dilute salt solution, which dissolves the enzyme. To find out what the nature of the enzyme may be, a small amount of the solution just prepared above, free of residue, is added to a solution of a substance, as starch, fat, or proteid, which an enzyme may decompose. After the course of a few hours the mixture is "tested for the splitting products of the respective substance added. If such be found and none were in either solution when kept separate, it may be safely concluded that an enzyme has been discovered in the tissues examined. Very likely it can be demonstrated that the tissue contains more than one ferment, by showing that the tissue extract will split more than one class of substances.
It has been but recently discovered that enzymes or, better, proenzymes have an interaction. The pure secretion from the pancreas does not digest proteids. The unadulterated juices from the intestinal wall do not split up proteids. But a mixture of the two secretions possesses marked proteolytic powers. This phenomenon has also been observed with other ferments.
It has been known for years that certain finely divided metals, like silver, platinum, gold and others, possess the property of accelerating some of the reactions of, or chemical changes in, inorganic chemistry. As an example—if any one of the above metals be added to a solution of hydrogen dioxide, the compound is decomposed into its constituents, water and oxygen. It remained, however, till recent years for a young man working in the physiological laboratory of one of our great universities to show that these finely divided metals, elements of the inorganic world, could perform the function of a body ferment. Finely powdered platinum prepared by precipitation—known as platinum black—when added to a simple fat, decomposes it, in the same manner as a body enzyme would do. The metal has practically all the ​characteristics of an organic enzyme. It digests the fat; it rebuilds fat from the component parts, i. e., its action is reversible; it is affected similarly by temperature changes and chemicals.
Another parallelism exists between the "vital" and inorganic phenomena, in the action of the salivary juice and acids on starch. The starch is to a greater or less extent digested in the mouth by virtue of a starch-splitting enzyme of the saliva. The same thing occurs if the starch and saliva are put together in a test tube. Acids will also digest starch. There is one marked difference, however, between the two. Enzymes act best at body temperature or a little above, while acids require boiling for their optimum action.
The temperature at which ferments act best is usually a little above the temperature of the body to which they belong. The optimum temperature for the action of enzymes of cold-blooded animals is below that for warm-blooded animals. A rise of twenty or thirty degrees above the optimum temperature destroys the ferments. A lowering of the temperature unless to the extreme does not kill; it only inhibits. The enzymes regain their function when the temperature returns to normal.
Many drugs have a very decided influence upon the fermentative processes. Of recent years this problem has occupied the mind and time of a number of physiologists. It is evident that this is a question of vital importance, on account of the general distribution of enzymes in the body, and the common introduction of drugs into the body. Very much too little is known, by even the scientific physician of to-day, regarding the action of drugs on the enzymes of the body. Some chemicals when present with the enzyme increase its power to do work; others decrease its power; and others stop it entirely. The concentration of the chemicals is of paramount importance. Most chemicals in concentrated solutions entirely prevent the action of ferments. On dilution the inhibitory power of the solutions decreases. In moderate concentrations some inhibit, more or less, and some stimulate, more or less. Both these processes usually decrease as the concentration of the respective solutions decrease. In some cases an effect may be noted in even very dilute solutions; a good example of such a solution is hydrocyanic acid.
If the author has been successful in the presentation of this subject, the reader should be impressed with the importance of the problem. The intimate relationship of enzymes with the vital processes renders an extensive knowledge of these bodies fundamental in the research into the phenomena of life.