work of Buchner proved him to be wrong.

The general mechanism of the action of the hydrolyzing enzymes is known. The old idea of de la Rive, that a molecule of enzyme combines transitorily with a molecule of substrate; the further idea, which may possibly go back to Engler, that the molecule of substrate is disrupted in the “strain” of the new combina­tion and that the broken fragments fall off or are easily knocked off by collision from the ferment molecule which is now ready to repeat the process, seems to be correct. On the assump­tion that the velocity of enzyme reac­tion is propor­tional to the mass of the enzyme and that de la Rive’s idea was correct, Van Slyke and Cullen were able to calculate the coefficients of the velocity of enzyme reac­tions for the fermenta­tion of urea and other substances, and the agreement between calculated and observed values was remarkable.16

While the hydrolytic action of enzymes is thus clear the synthesis in the cell is still a riddle. An interesting sugges­tion was made by van’t Hoff, who in 1898 expressed the idea that the hydrolytic enzymes should also act in the opposite direc­tion, namely synthetically. Thus it should not only be possible to digest proteins with pepsin but also to synthetize them from the products of diges­tion with the aid of the same enzyme. This expecta­tion was based on the idea that the enzyme did not alter the equilibrium between the hydrolyzed and non-hydrolyzed part of the substrate but only accelerated the rate with which the equilibrium was reached. Van’t Hoff’s idea omitted, however, the possibility that in the transitory combina­tion between enzyme molecule and substrate a change in the molecular configura­tion of the substrate or in the distribu­tion of intramolecular strain may take place. The first apparently complete confirma­tion of van’t Hoff’s sugges­tion appeared in the form of the synthesis of maltose from grape sugar by the enzyme maltase, which decomposes maltose into grape sugar. By adding the enzyme maltase from yeast to a forty per cent. solu­tion of glucose Croft Hill17 obtained a good yield of maltose. It turned out, however, that what he took for maltose was not this compound but an isomer, namely isomaltose, which has a different molecular configura­tion and cannot be hydrolyzed by the enzyme maltase.

Lactose is hydrolyzed from kephyr by an enzyme lactase into galactose and glucose; by adding this enzyme to galactose and glucose a synthesis was obtained not of lactose but of isolactose; the latter, however, is not decomposed by the enzyme lactase.

E. F. Armstrong has worked out a theory which tries to account for this striking phenomenon by assuming “that the enzyme has a specific influence in promoting the forma­tion of the biose which it cannot hydrolyze.”18 The theory is very ingenious and seems supported by fact. This then would lead to the result that certain hydrolytic enzymes may have a synthetic action but not in the manner suggested by van’t Hoff.

The principle enunciated by Armstrong, that in the synthetic action of hydrolytic enzymes not the original compound but an isomer is formed which can not be hydrolyzed by the enzyme, may possibly be of great importance in the understanding of life phenomena. It shows us how the cell can grow in the presence of hydrolytic enzymes and why in hunger the disintegra­tion of the cell material is so slow. It was at first thought that the forma­tion of isomers contradicted the idea of the reversible action of enzymes, but this is not the case; on the contrary, it supports it but makes an addi­tion which may solve the riddle of what Claude Bernard called the creative action of living matter. We shall come back to this problem in the last chapter.

Kastle and Loevenhart demonstrated the synthesis of a trace of ethylbutyrate by lipase if the latter enzyme was added to the products of the hydrolysis of ethylbutyrate, ethyl alcohol, and butyric acid by the same enzyme.19 Taylor20 obtained the synthesis of a slight amount of triolein