The regulatory roles of liver and kidney in cobalamin (vitamin BIZ) metabolism in the rat: the uptake and intracellular binding of cobalamin and the activity of the cobalamin-dependent enzymes in response to varying cobalamin supply

1. To examine possible regulatory roles of liver and kidney in cobalamin metabolism, specific activities of the two cobalamin-dependent enzymes, uptake in vivo of cyano [57Co]cobalamin ([57Co]CNCbl) and the binding of [57Co]Cbl to intracellular proteins were measured in normal, cobalamin-loaded and cobalamin-deficient rats. Cobalamin deficiency and cobalamin loading produced greater changes in cobalamin concentration in the kidney than in the liver. 2. Although cobalamin deficiency resulted in a decrease in total methylmalonyl-coenzyme A mutase (methylmalonyl-CoA mutase) in both organs, cobalamin loading had no effect. Neither deficiency nor loading altered total methyltransferase activity. The holoenzyme activities of both enzymes correlated with changes in tissue cobalamin levels. 3. Uptake of [57Co]Cbl indicated that the kidney, in contrast to the liver, increased its uptake during loading and reduced it during deficiency, suggesting a possible regulatory role for this organ. 4. In the normal rat, 24 h after injection of [57Co]CNCbl, 0.3% of the administered [57Co]Cbl was present in the liver as free cobalamin. By contrast, in the kidney, over 13% of the [57Co]Cbl