ENZYMES 



hormone elaborated by I lie kidney, hydrolyzes hypertensinogen, one 

 of the plasma proteins, with formation of a pressor substance. If this 

 possibility is confirmed, we would have the first identification of a 

 hormone with an enzyme function. Whatever the uncertainty about 

 hormones as enzymes, the evidence leaves no doubt that hormones 

 influence enzymic phenomena, e. g., the dramatic efTect of insulin* or 

 adrenalin on carbohydrate metabolism. In practically every instance, 

 hormone action has been boiled down to the regulation of some phase 

 of intermediary metabolism. Do hormones regulate by being enzymes 

 themselves, by influencing enzymes, or perhaps by controlling the 

 synthesis of enzymes? There are many indications which point to 

 some of the hormones controlling the synthesis of enzymes. But since 

 the synthesis of proteins represents one of the most obscure corners of 

 enzyme chemistry, there is little hope of any early clarification of the 

 precise role which hormones might play in synthesis. 



Oddly enough, our most precise knowledge of the way in which 

 the synthesis of enzymes is regulated has been acquired from the field 

 of genetics. The experimentation which has led to this knowledge 

 constitutes one of the most brilliant chapters of modern biology. 

 Geneticists have succeeded in demonstrating that single genes control 

 the syntheses of single enzymes. This implies that genes, like hor- 

 mones, are regulators of intermediary metabolism. Genes accom- 

 plish this regulation by controlling the synthesis of enzymes, whereas 

 hormones operate in ways as yet not classified. Genes and hormones 

 are distinguishable in another fundamental respect — hormones must 

 be synthesized by the respective endocrine glands, while genes are 

 autocatalytic and hence self-perpetuating. This autocatalytic property 

 of the gene resolves the dilemma that, if enzymes are needed to synthe- 

 size other enzymes, there must then be an infinite series of enzymes 

 making enzymes. But recognition of autocatalysis as a phenomenon 

 is a far cry from understanding the mechanism. As a matter of fact, 

 guesswork constitutes the sum and total of our knowledge of the way 

 in which certain protein molecules are able to reproduce themselves. 



* When this essay was in the proof stage, Cori and his group announced the 

 epoch-making discovery that insuHn reverses the inhibition of hexokinase produced 

 by one of the anterior pituitary hormones. In these two instances, at any rate, 

 hormones must be regarded as regulators of enzymes by virtue of their inhibiting 

 or releasing the inhibition of key enzymic processes. 



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