Vitamin b12 transport from food to the body's cells—a sophisticated, multistep pathway

ABSTRACT Vitamin B12 (B12; also known as cobalamin) is a cofactor in many metabolic processes; deficiency of this vitamin is associated with megaloblastic anaemia and various neurological

disorders. In contrast to many prokaryotes, humans and other mammals are unable to synthesize B12. Instead, a sophisticated pathway for specific uptake and transport of this molecule has

evolved. Failure in the gastrointestinal part of this pathway is the most common cause of nondietary-induced B12 deficiency disease. However, although less frequent, defects in cellular

processing and further downstream steps in the transport pathway are also known culprits of functional B12 deficiency. Biochemical and genetic approaches have identified novel proteins in

the B12 transport pathway—now known to involve more than 15 gene products—delineating a coherent pathway for B12 trafficking from food to the body's cells. Some of these gene products

are specifically dedicated to B12 transport, whereas others embrace additional roles, which explains the heterogeneity in the clinical picture of the many genetic disorders causing B12

deficiency. This Review describes basic and clinical features of this multistep pathway with emphasis on gastrointestinal transport of B12 and its importance in clinical medicine. KEY POINTS

* A coherent vitamin B12 (B12) transport pathway from food to the body's cells has now been delineated; the pathway includes an ABC transporter for cellular B12 efflux and a receptor

for uptake of B12-bound transcobalamin * More than 15 gene products are involved in B12 transport and/or processing; several new genes encoding intracellular proteins (including a potential

lysosomal transporter of B12) have been identified * Gastrointestinal uptake of B12 is via cubam, the complex of cubilin and amnionless * Novel genetic causes of B12 deficiency disease have

been clarified; many of the new proteins have been identified by positional cloning of the genes harbouring the disease-causing mutations * New diagnostic assays for B12 deficiency are being

developed; plasma level of holo-transcobalamin is a promising biomarker in combination with existing markers Access through your institution Buy or subscribe This is a preview of

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Ther._ 9, 3033–3040 (2010). Article  CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS This study was supported by the Novo Nordisk Foundation, the Lundbeck

Foundation, the Danish Medical Research Council and the European Research Council. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Biomedicine, Aarhus University, Ole Worms Allé

3, Building 1170, Aarhus, 8000, Denmark Marianne J. Nielsen, Mie R. Rasmussen, Christian B. F. Andersen & Søren K. Moestrup * Department of Clinical Biochemistry, Aarhus University

Hospital, Norrebrogade, Aarhus, 8000, Denmark Ebba Nexø Authors * Marianne J. Nielsen View author publications You can also search for this author inPubMed Google Scholar * Mie R. Rasmussen

View author publications You can also search for this author inPubMed Google Scholar * Christian B. F. Andersen View author publications You can also search for this author inPubMed Google

Scholar * Ebba Nexø View author publications You can also search for this author inPubMed Google Scholar * Søren K. Moestrup View author publications You can also search for this author

inPubMed Google Scholar CONTRIBUTIONS M. J. Nielsen contributed to the writing and reviewing/editing of the manuscript. M. R. Rasmussen and C. B. F. Andersen researched data. E. Nexø

researched data and contributed to reviewing/editing the manuscript. S. K. Moestrup contributed to all aspects of this manuscript. CORRESPONDING AUTHOR Correspondence to Søren K. Moestrup.

ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Nielsen,

M., Rasmussen, M., Andersen, C. _et al._ Vitamin B12 transport from food to the body's cells—a sophisticated, multistep pathway. _Nat Rev Gastroenterol Hepatol_ 9, 345–354 (2012).

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