STRUCTURE AND FUNCTION OF SOME ENZYMES 



By HUGO THEORELL 



BIOCHEMICAL DIVISION, THE NOBEL INSTITUTE FOR MEDICINE, STOCKHOLM, SWEDEN 



Somewhat more than 100 years ago, 1836, 

 the Swedish chemist Berzelius originated 

 the concept of catalysis and pointed out that 

 the catalytic reactions, which were begin- 

 ning at that time to be recognized in in- 

 organic chemistry, must be similar in prin- 

 ciple to the chemical reactions in the living 

 cells. This theory of Berzelius has later 

 been fully confirmed by the work of several 

 scientists, as Tamman, Arrhenius, Henri, 

 Michaelis, Hopkins, Wieland, and v. Euler, 

 but first and foremost by Warburg. The 

 analogy between inorganic catalysis and 

 enzymatic catalysis is evident from the fact 

 that in most cases the catalyst, as well as 

 the enzyme, exerts its action by means of 

 circle reactions, the enzymes forming re- 

 versible compounds, i.e., being oxidized and 

 reduced alternately. 



The name "enzyme" is due to Kiihne. 

 He and others, as Payen, Persoz, Schwann, 

 and Buchner, recognized that the reactions 

 in the cells are performed by substances 

 produced by the living cells, but not living 

 themselves. Our knowledge about the 

 chemical nature and function of enzymes is, 

 however, of a much more recent date. The 

 prerequisite for any deeper knowledge 

 about the chemical nature of any substance 

 is its preparation in a pure state. The first 

 enzyme obtained in this form was urease, 

 which was crystallized by J. B. Sumner in 

 1926. This important step solved one of the 

 questions about the enzymes insofar as it 

 proved this enzyme to be a protein. The 

 extensive work of J. H. Northrop and his 

 co-workers on the proteolytic enzymes dem- 

 onstrated the protein nature of this im- 

 portant group of enzymes. It may seem 

 nearly superfluous to point out the protein 

 nature of enzymes today, since nobody has 

 any doubt on that point; but the demon- 

 stration of the protein nature of enzymes 

 was a very important advance, considering 

 the fact that in the same year of 1926 when 

 Sumner crystallized urease, the German 



chemist Willstatter, in a lecture given in 

 the "Deutsche chemische Gesellschaf t, " 

 drew the conclusions from his extensive 

 work on enzymes that they could be neither 

 carbohydrates nor proteins, and that the 

 enzyme activity is due to some unknown 

 natural force. However, since that very 

 time, it has become evident that enzymes 

 are proteins nevertheless, and, furthermore, 

 that no new sort of natural force is involved 

 in their activity. We are today convinced 

 that enzymes perform chemical reactions of 

 essentially the same kind as those which we 

 know in organic chemistry. However, only 

 for some of the oxidation enzymes are we 

 able to give a picture of their action by 

 means of chemical formulas. This is at 

 present not the case for the hydrolytic 

 enzymes. The difference depends upon the 

 fact that we have found in the former, but 

 not in latter, so-called prosthetic groups. 

 This low-molecular part of the enzyme 

 molecule can be regarded as the seat of the 

 enzymatic action, because the circle reac- 

 tions take place there. The ferments which 

 contain heavy metals carry a stream of 

 electrons by means of the metal atom which 

 oscillates between two different oxidation 

 levels, such as ferrous ^ ferric, or cuprous 

 ^ cupric. The metal-free oxidation en- 

 zymes carry a stream of hydrogen from the 

 substrates toward the oxygen by means of 

 their ability to oscillate between the reduced 

 and the oxidized state, their prosthetic 

 groups (flavin compounds or nicotinic acid 

 amide compounds or others) taking up and 

 giving off hydrogen in the same w^ay that 

 well-known dyestuffs form leuco-com- 

 pounds with hydrogen, and may be oxidized 

 again. The protein part of the oxidation 

 enzymes has the function of differentiating 

 the prosthetic group for its special purpose. 

 Thus tlie same prosthetic group may occur 

 in enzymes of very different functions, such 

 as hemin in the respiratory pigment of 

 Warburg, the cytochromes, the catalases, 

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