Nephrol Dial Transplant (2003) 18: 1095-1100
© 2003 European Renal Association-European Dialysis and Transplant Association
Diversity in rat tissue accumulation of vitamin B12 supports a distinct role for the kidney in vitamin B12 homeostasis
1 Department of Cell Biology, Institute of Anatomy, University of Aarhus and 2 Department of Clinical Biochemistry, AKH, Aarhus University Hospital, Aarhus, Denmark
Background. Vitamin B12 in plasma is complexed to the carrier proteins transcobalamin (TC) and haptocorrin. The TC–B12 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 B12. The present study investigates the role of the rodent kidney in B12 homeostasis by examining the distribution of vitamin B12 in rats during vitamin B12 depletion or B12 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 B12 supplemented with s.c. injections of B12. Twenty four hours prior to sacrifice, all animals were injected with [57Co]B12. The vitamin contents of kidneys, liver, spleen, brain, testis, intestine, skeletal muscle, serum and urine were analysed. Both total tissue vitamin B12 accumulation and [57Co]B12 were determined to compare steady-state B12 and the distribution of an acutely injected dose. In the kidney, free and protein-bound B12 was determined by gel filtration.
Results. The rat kidneys accumulated more B12 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 B12 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 B12 metabolism. We propose a model for rat tissue uptake consistent with the presence of two different TC–B12 receptors and renal uptake following filtration of TC–B12 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 B12 deficiency.
Keywords: cobalamin; megalin; renal physiology; vitamin metabolism
Correspondence and offprint requests to: Henrik Birn, MD, PhD, Department of Cell Biology, Institute of Anatomy, University of Aarhus, Building 234, DK-8000 Aarhus C, Denmark. Email: hb{at}ana.au.dk
The term vitamin B12 is generally used for cyanocobalamin only. However, since the different forms of cobalamin may be converted into each other, the term vitamin B12 or B12 herein includes all forms of cobalamin identified by our assay, including also adenosylcobalamin, methylcobalamin and hydroxycobalamin.
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