ENZYMES 139 



enzyme-substrate system, their major value lies in work with enzyme 

 inhibitors (see page 145). 



Cofactors 



Many enzymes act on their substrates only in the presence of addi- 

 tional materials called cofactors. These substances are readily sep- 

 arated from the enzymes themselves and are usually not isolated with 

 the enzymes. Thus cofactors are distinguished from the firmly bound 

 prosthetic groups. The cofactors are readily dialyzable, small mole- 

 cules that are relatively heat stable. At least in some cases, they are 

 known to form complexes with their respective enzymes during the 

 course of enzymatic activity. These complexes are relatively unstable, 

 with equilibrium points permitting easy removal of the cofactors. 



The cofactors may be divided into two groups. When the cofactor 

 itself undergoes a definite chemical reaction, it is usually called a 

 coenzyme. Such changes would classify the coenzymes with substrates, 

 and sometimes there may be no real distinction. However, the chem- 

 ical roles of the coenzymes were unknown when they were first discov- 

 ered, so the term has been retained. Besides, the number of different 

 coenzymes is much more limited than the number of substrates, and a 

 single coenzyme functions with many different enzymes and substrates. 

 Finally, though the structure of a coenzyme is changed by an en- 

 zymatic reaction, in a functioning cell a subsequent enzymatic process 

 restores the coenzyme to its original form. Substrates usually undergo 

 successive transformations, seldom being re-formed except in certain 

 cyclic processes. Thus the use of the special term coenzyme seems justi- 

 fied. 



It turns out that several of the water-soluble vitamins are important 

 structural components of certain coenzymes. Since fifteen or more 

 coenzymes are now known and most are rather complex in structure, 

 only two examples will be presented here. These two have been 

 chosen from among coenzymes involved in quite diverse roles, includ- 

 ing the transfers of phosphate, hydrogen and electrons, and acyl 

 groups; the amination, deamination, and decarboxylation of amino 

 acids; the decarboxylation of keto acids; and the isomerization of 

 carbohydrate derivatives. One coenzyme, variously called diphospho- 

 pyridine nucleotide, DPN + , coenzyme I, cozymase, or codehydrogen- 

 ase I, participates with specific enzymes in a number of oxidation- 

 reduction systems of great metabolic importance. The coenzyme 

 itself is oxidized or reduced according to the following scheme: 



