ENZYMES 



273 



which decomposes acetylcholine; as a result, the latter accumulates and 

 causes increased stimulation. 



Activation 



Zymogens. A number of enzymes are secreted in the form of inactive 

 precursors known as zymogens. For each zymogen there is some reagent 

 that can change it into the active enzyme. To illustrate, pepsinogen, the 

 zymogen of pepsin, is slowly converted into active pepsin by hydrogen 

 ions, but it is rapidly activated by pepsin itself; that is, the activation 

 is autocatalytic. Chymotrypsinogen is converted into chymotrypsin by 

 trypsin. The conversion of trypsinogen to the active form is autocata- 

 lytic, i.e., by trypsin itself. 



Ions. Certain enzymes can be separated into two fractions by dialysis. 

 Either fraction alone is inactive, but upon recombination the activity is 

 restored. The portion of the enzyme that can pass through the membrane 

 has a much smaller molecular weight than the remaining part. This 

 dialyzable portion is considered as a cofactor which is necessary for the 

 activity of the total enzyme. In some cases more drastic conditions 

 than simple dialysis must be employed to separate the cofactor from 

 the apoenzyme; for example, treatment with acid in ammonium sulfate 

 solution in the case of certain flavo-proteins. In some enzymes the 

 cofactor is so tightly bound that it has not been yet possible to remove 

 it without destroying the enzyme. 



In many cases the cofactor is simply a metallic ion. For example, 

 Mn++, Co + + , or Zn + + have been found to be activators for certain 

 peptidases. The theory has been proposed that the metal ions form 

 coordination compounds and act as bridges to bring substrate and enzyme 

 together. Certain enzymes have a characteristic anion requirement, e.g., 

 salivary amylase is activated by chloride. 



Coenzymes. Another group of cofactors are organic compounds which 

 are called coenzymes. The study of coenzymes has received much atten- 

 tion by biochemists for the past 20 years, and the chemical structures 

 of many of them have been determined. The cofactors required by 

 several enzymes are given in Table 10-1. 



1. Cocarboxylase. It has been pointed out previously (p. 227) that 

 thiamine is required for the metabolism of carbohydrates, and particularly 

 of pyruvic acid. The reason for this requirement is that the enzyme which 



CHa Q O 



Is=C-NH2 c=C-CH5CH— OP-0— P-0- 



/ I I 



o o 



H3C-C C-CH,-+N 



N-CH Y ^ H H 



H 



Fig. 10-4. Thiamine pyrophosphate (cocarboxylase). 



