New insights into carrier binding and epithelial uptake of the erythropoietic nutrients cobalamin and folate.
OBJECTIVE
In addition to malnutrition several genetic and acquired conditions may affect the homeostasis of cobalamin (vitamin B12) and folate, leading to megaloblastic anemia and other diseases. The present review describes new insight into protein handling of cobalamin and folate.


RESULTS
The recent solution of the three-dimensional structure of the cobalamin binder transcobalamin shows two separate domains enclosing the vitamin. This structure apparently also applies for the other homologous cobalamin binders, intrinsic factor and haptocorrin. Genetic studies of inherited cobalamin malabsorption and biochemical studies have now revealed that the functional receptor for uptake of intrinsic factor-vitamin cobalamin complexes also is a complex itself consisting of two different gene products, cubilin and amnionless. A role in folate uptake of megalin, an endocytic receptor for epithelial uptake of various proteins including transcobalamin, is now also indicated by the observation that megalin can mediate uptake of soluble folate receptor.


CONCLUSIONS
New data show the structure of cobalamin carriers and reveal novel proteins involved in the epithelial uptake of cobalamin and folate. Genetic abnormalities in three different genes encoding proteins in the epithelial uptake of cobalamin are now known to cause malabsorption of cobalamin and megaloblastic anemia.
Department of Medical Biochemistry, University of Aarhus, Denmark. skm@biokemi.au.dk
Søren K
SK
Moestrup
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology*; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D011485:Protein Binding; D014805:Vitamin B 12 / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*
D002352:Carrier Proteins; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D005492:Folic Acid; D014805:Vitamin B 12