Diversity in rat tissue accumulation of vitamin B12 supports a distinct role for the kidney in vitamin B12 homeostasis

Background. Vitamin B-12 in plasma is complexed to the carrier proteins transcobalamin (TC) and haptocorrin. The TC-B-12 complex is filtered in the glomeruli and reabsorbed in the renal tubules by receptor-mediated endocytosis, providing a route for a significant renal accumulation of vitamin B-12. The present study investigates the role of the rodent kidney in B-12 homeostasis by examining the distribution of vitamin B-12 in rats during vitamin B-12 depletion or B-12 load, and compares kidney accumulation with the vitamin distribution in other tissues including brain, liver, testes, intestine, spleen and plasma. Methods. Fifteen rats were fed on a diet containing different concentrations of B-12 supplemented with s.c. injections of B-12. Twenty four hours prior to sacrifice, all animals were injected with [Co-57]B-12. The vitamin contents of kidneys, liver, spleen, brain, testis, intestine, skeletal muscle, serum and urine were analysed. Both total tissue vitamin B-12 accumulation and [57Co]B-12 were determined to compare steady-state B-12 and the distribution of an acutely injected dose. In the kidney, free and protein-bound B-12 was determined by gel filtration. Results. The rat kidneys accumulated more B-12 during normal and loaded conditions than any other tissue. A 110-fold increase in vitamin content was observed from the deficient to the loaded conditions in the kidney compared with a 3.5-fold increase in the liver. In contrast to all other organs, significantly smaller amounts of acutely injected B-12 accumulated in the kidneys in the vitamin-deprived state compared with both the normal and the vitamin-loaded condition. Conclusions. The present study suggests a significant role for the rodent kidney in vitamin B-12 metabolism. We propose a model for rat tissue uptake consistent with the presence of two different TC-B-12 receptors and renal uptake following filtration of TC-B-12 in the glomeruli. The presented model allows for the reduced renal uptake and accumulation in vitamin-deprived conditions, thus reserving the vitamin for other tissues, including nerve tissue and bone marrow, which are more sensitive to vitamin B-12 deficiency.