1. To clarify further the role of the pancreas in cobalamin absorption we characterized pure human pancreatic juice. With isolated exceptions, samples of the pure juice contained little cobalamin and had low cobalamin-binding capacities.

2. Ten of 13 specimens of pure human pancreatic juice collected in the cholecystokinin—pancreozymin phase were active against R binder from other sources and degraded them in vitro, as did four of ten secretin phase specimens. Moreover, enteropeptidase activated all but one of the inactive specimens. The sole refractory specimen was from a healthy volunteer. At the same time, the pure pancreatic juices from all three patients with pancreatic insufficiency were active against R binder, illustrating a surprising overlap in this property between healthy and abnormal subjects.

3. Trypsin, although active against R binder, did not fully account for the activity of pure human pancreatic juice, since aprotinin, which inhibited trypsin activity, inhibited the juice poorly. Furthermore, the activity of the juice did not always correlate with its trypsin activity. Chymotrypsin and elastase were active only at very high concentrations.

4. Pure human pancreatic juice affected salivary, gastric, biliary and endogenous pancreatic R binders in two ways. It converted them into a 70 000 mol. wt. molecule. It also produced what seemed to be small fragments and free cobalamin but which may have been primarily an easily dissociable binder—cobalamin bond. The former effect was particularly prominent when gastric R binder was the substrate, whereas saliva R binder seemed more susceptible to the second effect.

5. Holo-R binders were consistently much more resistant than apo-R binders to pure human pancreatic juice. The only exception was bile, whose holo- and apo-R binders appeared equally susceptible.

6. Our findings with pure human materials confirm that the pancreas degrades R binder. However, this activity seems intact in patients with pancreatic insufficiency, at least in vitro. The pancreatic role may be more important in destroying apo-R binder than in releasing cobalamin delivered to the intestine already bound to R binder. In addition, the ready liberation by pure human pancreatic juice of bound cobalamin in bile suggests that pancreatic juice is important in the hepatic recirculation of cobalamin.

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