284 



NA TURE 



[July 23, 1903 



of the vital process of the organism itself — that the sugar 

 taken in as food by the organism is finally thrown out in 

 the form of carbon dioxide and alcohol ; it is now clear, 

 however, that the formation of these two products is in 

 no way a vital process. By triturating yeast with powdered 

 quartz, so as to shatter the cell walls, and expressing the 

 pulp thus produced, Buchner has succeeded in obtaining a 

 solution which, when mixed with sugar solution, converts 

 the sugar into carbon dioxide and alcohol. The ferment- 

 ation is therefore not a vital phenomenon, but is a chemical 

 action induced by some non-living substance contained in 

 the expressed juice of the yeast cells. This substance — 

 zymase — has been isolated in the solid state, and belongs 

 to the class of substances known as unorganised ferments 

 or enzymes. Although many enzymes are known, each 

 active in inducing the occurrence of some particular chemical 

 change or changes, nothing is as yet known as to their 

 molecular constitutions ; ages of evolution have given such 

 complexity to these substances that a century or less of 

 chemical investigation has contributed practically nothing 

 towards elucidating their nature. 



During the investigation of cases of animal and vegetable 

 vital activity, great numbers of instances of the action 

 of enzymes have been found, the function of the enzyme 

 being to bring about the molecular degradation and, in 

 certain cases, the molecular complication, of more or less 

 complex ipaterials used or produced in the organism. As 

 an example of molecular degradation due primarily to 

 enzymic action, the action of zymase on grape-sugar — 

 d-glucose — may be quoted. In aqueous solution, one mole- 

 cule of grape-sugar becomes directly converted into two 

 molecules of alcohol and two molecules of carbon dioxide, 

 in accordance with the equation 



C.Hi,0, = 2CjH,0+2CO„ 



by the enzyme zymase. The enzyme itself suffers no 

 permanent change as a result of exercising the power of 

 causing this chemical reaction to take place, so that a 

 comparatively minute quantity of the enzyme, acting for 

 a more or less prolonged period, is able to convert an un- 

 limited quantity of grape-sugar into alcohol and carbon 

 dioxide. The power which the enzyme possesses of inducing 

 the occurrence of some chemical reaction which otherwise 

 does not take place is not peculiar to enzymes ; many sub- 

 stances, which are all classed together as the so-called 

 catalytic agents, are known to exercise the same sort of 

 influence in assisting a chemical reaction to occur. Thus 

 the action of finely divided platinum in causing certain 

 inflammable gases to ignite in air at the ordinary tempera- 

 ture is a catalytic action. The particular function exer- 

 cised by enzymes in animal or vegetable life consists in 

 bringing about chemical change, quietly and continuously, 

 without necessitating the application of any violent chemical 

 effects such as we are in the habit of using in the labor- 

 atory. Although they proceed so quietly, the chemical 

 changes thus effected are, in certain cases, changes which 

 we have not yet succeeded in carrying out without the 

 assistance of an enzyme ; in the conversion of sugar into 

 alcohol and carbon dioxide, zymase is performing a re- 

 action which has never yet been brought about by the use 

 of the ordinary laboratory methods. 



Without quoting more specific instances, it may be gener- 

 ally stated that most of the cases of enzymic action hitherto 

 investigated are cases in which a large molecular complex 

 is degraded or broken down into substances of lower mole- 

 cular weight. But it is important to note that the organism 

 is also the seat of processes which result in the building 

 up of very complex molecules from simpler ones, such, for 

 instance, as the formation of starch from carbon dioxide 

 and water. A specific case in which enzymic action leads 

 to the production of a complex substance from simpler ones 

 • has been recently worked out by Fischer and Armstrong, 

 who show that the enzyme, lactase, converts the sugar 

 galactose, C^^^O^^, into a new sugar, isolactose, CijHjaOji, 

 of nearly twice the molecular weight of the former." 



All the enzymes with which we are acquainted appear to 

 be enantiomorphous bodies ; they are, perhaps, substances 

 lo which no definite molecular composition can ever be 

 assigned, inasmuch as they may be systems consisting of a 

 number of different true chemical compounds, the system be- 



NO. 1760, VOL. 68] 



ing one which becomes endowed with extraordinary chemical! 

 activity when placed in a suitable environment. The enan- 

 tiomorphism of the enzyme has been repeatedly demon- 

 strated during the course of Emil Fischer's remarkable- 

 synthetic work on the sugars. Fischer succeeded in pre- 

 paring fruit-sugar or fructose by purely synthetical methods- 

 as a mixture of the dextro- and the laevo-isomerides ; in order 

 to_ isolate the previously unknown /-fructose, he applied the 

 third Pasteur method in that he cultivated a yeast in the 

 solution of the compensated fructose. The yeast enzyme 

 —presumably zymase — has arrived at its present stage of 

 development by passing through countless generations, all! 

 of which have been fed upon sugars of the dextro-configura- 

 tion, these being the only ones occurring in Nature. In 

 Fischer's experiment the enzyme therefore readily devoured 

 the d-fructose, but refused to touch the Z-fructose, which 

 had never before been presented to it. The Z-fructose was, 

 of course, subsequently isolated from the solution. The- 

 need for compatibility between the enzyme and the material 

 upon which it has to act is very clearly illustrated by 

 considering the effect of yeast upon a number of optically 

 active and isomeric sugars. In the table (Fig. 9) are given- 

 the constitutions of a number of sugars of the composition- 

 C6Hj20e, the configurations of the three or four asymmetric 

 carbon atoms present in the molecule being indicated hj 

 writing the hydrogen atoms on the right or the left of the 

 figure, as the case may be ; the right or left hands indicate 

 which asymmetric carbon atoms are of similar, and which 

 of opposed, configurations. 





d-Glucose 



d-Mannose 



d-Galactose d-Talose 



Fig. 9. 



The beer yeast ferments d-glucose, d-mannose and d-fruc- 

 tose, each of which contains in the molecule a set of three 

 asymmetric carbon atoms of similar configuration, with 

 about equal readiness ; d-galactose is, however, only fer- 

 mented ■ with difficulty — in the set of three asymmetric 

 carbon atoms referred to, it contains one differing in con- 

 figuration from the corresponding one in the three easily 

 fermentable sugars. d-Talose, in which two of the three 

 asymmetric carbon atoms differ in configuration from the 

 corresponding carbon atoms in d-fructose, is quite un- 

 affected by the yeast. It is just as if the enzyme were 

 provided with three hands, in the order right, right, left, 

 to enable it to grip the sugar molecule and commence 

 tearing it to pieces ; with these three hands it grips the 

 corresponding hands — also of the configuration and order, 

 right, right, left, of the first three sugars. The enzyme 

 can, however, only grip the d-galactose molecule by two 

 hands, and so obtains a less firm hold. Owing to the 

 greater incompatibility between the zymase and the d-talose, 

 the former obtains too feeble a hold on the latter to enable 

 it to make a successful assault, and the sugar therefore 

 remains unfermented. 



The fact that the chemical reactions of animal and vege- 

 table physiology consist, in the main, of the production or 

 destruction of optically active substances through the agency 

 of enantiomorphous enzymes is one of enormous import- 

 ance. The complex substances concerned, such as starches,, 

 albumins and food-stuffs generally, occur in Nature in but 



