104 - The Cell 





Fig. 5-1. Crystals of purified pepsin. (Courtesy of 

 J. A. Northrop, Rockefeller Institute for Medical Re- 

 search.) 



enzyme has an essential protein component, 

 without which the enzyme loses all catalytic 

 power. Indeed, some enzymes (for example, 

 pepsin and trypsin, Table 5-1) are solely pro- 

 tein. Many others, however, consist of a pro- 

 tein part, called the apoenzyme, and a non- 

 protein part, called a cofactor. Quite a few 

 such cofactors have been identified. Each has 

 proved to be a relatively simple phosphory- 

 lated substance, chemically united to some 

 one or another of the vitamin compounds, 

 such as niacin, thiamine, riboflavin, etc. 

 (Chap. 18). In fact, recent developments indi- 

 cate that the principal role of most vitamins 

 is to act as cofactors in various metabolic en- 

 zyme systems — as will be discussed more fully 

 in Chapters 8 and 1 8. 



Coenzymes vs. Prosthetic Groups. The pro- 

 tein and nonprotein parts, in some enzymes 

 (for example, succinic dehydrogenase, p. 108), 

 are very firmly united, and a separation of 

 the parts leads to an irreversible loss of cata- 

 lytic activity. In such cases, the nonprotein 

 cofactor is spoken of as a prosthetic group, 

 and the total enzyme complex can be re- 

 garded as a conjugated protein. However, 

 in other cases (for example, lactic dehydro- 

 genase, p. 108), the affiliation is loose, and full 

 activity can be restored after the parts have 

 been separated and then brought together 



again. Such readily separable cofactors, in- 

 deed, are called coenzymes. Moreover, several 

 cases are known (for example, coenzyme A, 

 p. 153) wherein the same coenzyme may team 

 up with more than one apoenzyme, thus cata- 

 lyzing several different metabolic reactions. 

 This indicates that the specificity of enzyme 

 action (p. 108) is determined mainly by the 

 structural configuration of the protein part 

 of each different enzyme complex. 



HOW ENZYMES ACT 



The precise mechanisms of enzyme catalysis 

 are still not fully understood, although many 

 investigators are concentrating on this area. 

 The recent evidence indicates that frequently 

 (perhaps always) the enzyme and substrate 

 molecules combine together, rapidly and mo- 

 mentarily forming a highly unstable inter- 

 mediary enzyme-substrate compound (Fig. 5- 

 2). Almost instantaneously thereafter, how- 

 ever, the enzyme-substrate compound de- 

 composes, restoring the free enzyme and 

 liberating the end products of the reaction 

 (Fig. 5-2). The evidence further indicates that 

 energy is generated by the enzyme-substrate 

 union. Presumably this energy serves to raise 

 the energy level of the substrate molecule 

 (Fig. 5-2), inducing what max be termed an 

 activated state, in which certain of the bonds 

 of its molecular structure are more suscepti- 

 ble to rupture. Moreover, union between 

 enzyme and substrate molecules often seems 

 to depend upon a mutual compatibility, or 

 reciprocal fit between the molecular struc- 

 ture of the enzyme and that of the particular 

 substrate. More specifically, the configuration 

 of some particular part of the en/\me mole- 

 cule, which is known as the catalvtic site, 

 must conform in some wax to the confieura- 

 tion of some part of the substrate molecule 

 —more or less in the fashion that a key must 

 be fitted to its lock (Fig. 5-2). 



Enzyme-Substrate Combinations. Almost 

 50 years ago Leonor Michaelis, of the Rocke- 

 feller Institute, first proposed that enzyme- 

 substrate combinations are formed during 



