ON THE INACTIVATION OF FERMENTS AND THE PRODUCTION OF ANTIFERMENTS IN VITRO IN THE PRESENCE OF ARTIFICIAL MEMBRANES

It has been established that it is possible to inactivate a number of ferments by keeping them in contact with artificial membranes, especially with collodion. Most ferments which have thus been inactivated have at the same time acquired inhibitive properties. It is thus possible to imitate with artificial membranes the action of living bacterial membranes on ferments and immune substances. It seems reasonable to conclude that the living membranes of the animal body have a similar power, and that this is the means by which the organism rids itself of the ferments which it is constantly producing. Such a view affords an explanation of the existence of antiferments. The inactivation of ferments by membranes is not due to simple absorption. There is no evidence of saturation of the membrane; on the contrary, its inactivating power appears to improve by repeated use. And further, only a trace of ferment can be recovered from the membrane. The inhibitive power of inactivated ferments is due, partly at any rate, to substances preformed in the solution. This is clear from the fact that the inhibition is most marked with such preparations as stomach extracts, which are known to contain inhibitive substances in considerable amount. But sufficient inhibition appears also after removal of these inhibitive substances, and we must conclude that the ferment itself is changed by contact with a membrane into a substance having an inhibiting power. This conclusion is further supported by the fact that the repeated use of a membrane appears to improve its inactivating power. The question arises whether the inhibiting substance acts as a true antiferment, i.e. by combining with the ferment, or by acting on the substrate as Cramer and Bearn suggested for their zymoids. The fact that collodion‐pepsin is inactive against edestin, but not inhibitive, while inhibitive if fibrin or serum is used, tends to show that the inhibition is due to an action on the substrate and not to a neutralisation of the active ferment. This view is confirmed by the fact that the inhibitive action of collodion‐trypsin is more marked when added first to the substrate, than when added first to the ferment. Old stomach extracts which had been kept for 7–9 months underwent a spontaneous inactivation, becoming at the same time powerfully inhibitive to fresh ferment, a behaviour strongly suggestive of a deterioration from enzyme to zymoid. Whether, however, the inhibitive action of ferments which have been treated with collodion is entirely due to zymoid formation is somewhat uncertain. An indication of recovery on the part of inactivated pepsin has been noticed which is very suggestive of the recovery of ferments after combination with antiferments, which has been described by Bredig (32) for inorganic ferments, Fuld and Spiro (33) for serum antirennet, and Dastre and Stassano (34) for the antitrypsin of Weinland. These antiferments are absorbed into the pores of the ferment, thereby inhibiting it, but in the absorbed state are peculiarly liable to decomposition, the ferment wholly recovering in this way, and in the case of inorganic ferments becoming actually somewhat “immune” to the action of additional antiferment. The recovery of inactivated pepsin is, however, slight, and is not comparable with the complete recovery noticed by other authors in the case of pure true antiferments. While it is sufficient to indicate that some pepsin does still exist in the apparently inactive solution and therefore renders the existence of a true antiferment probable, it does not exclude the influence of a zymoid, to which undoubtedly the greater part of the inhibition is due.