THE BIOCHEMICAL PROCESSES OF DIGESTION 519 



The digestive action of hydrochloric acid is closely linked with that of 

 pepsin, with which it will, therefore, be considered. 



The Action of Pepsin 



It is commonly believed that before its secretion pepsin exists in the 

 cells of the gastric glands as zymogen granules. The chief evidence for 

 this belief appears to be that after considerable activity the amount of 

 zymogen granules in the gland cells is found to be decidedly dimin- 

 ished. By such an hypothesis it is easy to explain certain interesting 

 results concerning the effect of weak alkali on the activities of extracts 

 of the mucous membrane of the stomach. When the mucous membrane 

 is extracted with weak acids, the extract is very active proteolytically. 

 If this so-called pepsin solution be made faintly alkaline, or even only 

 neutralized, and again made acid, it will be found to have lost much, 

 if not all, of its activity. On the other hand, an aqueous extract may be 

 rendered slightly alkaline for a short time and still display its digestive 

 activity on subsequent acidification. The extract made with water is 

 therefore much more resistant toward alkali than that made with weak 

 acid, and the difference is explained on the supposition that the watery 

 extract contains pepsinogen, whereas the acid extract contains pepsin. 



It is believed that there are several varieties of pepsin, because the optimum con- 

 centration of acid in which pepsin, derived from the stomachs of different animals, acts 

 is not always the same. Pepsin of the dog, for example, acts best in a hydrogen-ion 

 concentration corresponding to that of a 0.05 N. hydrochloric acid solution, whereas 

 that of the human stomach works best at a concentration of 0.03 N. Different pepsin 

 solutions also show a difference with regard to the optimum temperature at which they 

 act, and with regard to the nature of the protein which they most readily attack. Thus, 

 the pepsin of a calf's stomach digests casein very rapidly, but coagulated egg white 

 only slowly, whereas the pepsin of the pig's stomach acts on both these proteins at 

 about the same rate. 



It is well known that the activity of pepsin can proceed only in the presence of 

 acids, but this action of acids does not appear to depend on the hydrogen-ion concen- 

 tration alone, for when equal quantities of the same pepsin are mixed with quantities 

 of different acids so that the hydrogen-ion concentration of the mixtures is uniform, 

 it is found that digestion proceeds most rapidly with hydrochloric acid and least 

 rapidly with sulphuric acid. The SO 4 ion seems, therefore, to be unfavorable for 

 peptic activities. The acid seems to combine with the protein before the pepsin attacks 

 the latter; for, if we first combine the protein with acid and then wash away all 

 traces of free acid, the protein can be digested in a neutral pepsin solution without the 

 liberation of any free acid. 



There is evidence to show that pepsin itself also becomes combined with the pro- 

 tein during the digestive process. If a piece of protein such as fibrin be immersed 

 in a solution of pepsin and then taken out and washed thoroughly to get rid of all 

 adherent pepsin, it will be found, on placing it in a hydrochloric acid solution of the 

 proper strength, that peptic digestion proceeds. Advantage may be taken of this fact 

 to separate pepsin from a solution, but the best protein to use for this purpose is 



