Portal and biliary phases of enterohepatic circulation of corrinoids in humans

The assimilation of labeled cobalamin and the transport of corrinoids in portal blood, peripheral venous blood, and bile were studied in eight cholecystectomized patients, after ingestion of a dose of cyano[57Co]cobalamin (0.5 μCi). The radioactivity appeared in the portal vein after a delay of 1.5–2 hours and in the peripheral vein 1 hour later. In bile, it reached a maximum at 24–72 hours; the excreted cobalamin corresponded to 1.42% ± 0.92% of the dose ingested. The output of total corrinoids was 1.85 nmol/day. The high-performance liquid chromatography analysis of bile showed the presence of methylcobalamin, 5′-deoxyadenosylcobalamin, hydroxocobalamin, and an unknown corrinoid. This corrinoid bound to R binder but not to the intrinsic factor, and it had the same retention time as cobinamide. The R binder was the single cobalaminbinding protein found in bile. It was completely saturated in some periods of bile secretion. The corrinoids corresponding to such a period were eluted in Sephacryl S 300 gel filtration (Pharmacia Fine Chemicals, Uppsala, Sweden) in two peaks corresponding to saturated R binder and to free cobalamin. The mean level of total corrinoid was significantly higher in the portal vein (593 ± 238 pmol/L) than in the peripheral vein (376 ± 114 pmol/L) (P< 0.01). This “cobalamin analogue” fraction was hypothetical because it was calculated from the difference between total corrinoid concentration and the so called “true cobalamin” concentration. This difference corresponded to the cobalamin analogue fraction. These data show that bile removes not only cobalamin but also cobalamin analogues and that R binder is the single carrier protein involved in their excretion.