In vivo evidence that cobalamin is absorbed by receptor-mediated endocytosis in the mouse.

This study examines the mechanism of cobalamin absorption in the context of receptor-mediated endocytosis. Uptake, the amount of cobalamin that left the intestinal lumen, and transport, the component that was located in organs beyond the intestine, were measured after feeding saturating doses of [57Co]cobalamin to mice. Uptake from a 40-ng dose of [57Co]cobalamin at 1 h was 18.6 +/- 6.3 ng (mean +/- SD; n = 6). When the dose was given 1 h after 40 ng of unlabeled cobalamin, uptake was 18.5 +/- 1.5 ng, n = 6, indicating rapid clearance of the surface receptors. Transport of the initial and of a subsequent dose of cobalamin could not be detected for 2 h but the amounts and rates of transport were similar. Oral chloroquine and intraperitoneal cycloheximide reduced transport at 4 h to 4.3 +/- 1.6 ng, n = 8 and 5.6 +/- 2.4 ng, n = 7, respectively. Control values were 14.3 +/- 1.3 ng, n = 8. These results indicate that the transport of cobalamin involves a series of compartments, one of which may be lysosomal, and that there is a requirement for new protein synthesis.