The catabolism of homologous and heterologous 7S gamma globulin fragments obtained by pepsin and papain digestion was studied in rabbits, guinea pigs, and mice. The elimination from the circulation of I* labeled gamma globulin fragments was followed and the urinary excretion of the total and protein-bound I* activity determined.
Evidence is presented that the molecular structure responsible for the catabolism of 7S gamma globulin is located in papain fragment III. The elimination of papain fragment III was slow and closely related to the intact gamma globulin, whereas the pepsin fragment and papain fragments I and II were rapidly eliminated and catabolized in all species examined.
Prolonged incubation with cysteine altered papain fragment III as shown by a rapid catabolism of a large portion of incubated fragment III within 24 hours after injection.
Small amounts of intact RGG and RGG papain fragment III were excreted as protein-bound I* activity in the urine. On the other hand, large amounts of the pepsin fragment and papain fragments I and II of RGG were excreted as protein-bound I* activity in the urine. The possibility of a molecular structure present in papain fragment III, which may be responsible for tubular reabsorption in the kidney, is discussed. The rate of urinary excretion of fragments obtained from RGG was different from that of fragments obtained from gamma globulin of several other species. In general, small amounts of the pepsin fragment and papain fragment III obtained from gamma globulin other than RGG were excreted as protein-bound I* activity. The amounts of fragment I* excreted as protein-bound I* activity depended on the species in which it was injected, as well as the source of the gamma globulin.
The rapid catabolism of the pepsin fragment and papain fragments I or II which bear antibody-combining sites suggest that their use for the prophylactic treatment of tetanus and diphtheria in man is limited.