Journal of Molecular Medicine

, Volume 88, Issue 5, pp 459–466

Insights into lysosomal cobalamin trafficking: lessons learned from cblF disease

  • Susann Gailus
  • Wolfgang Höhne
  • Bruno Gasnier
  • Peter Nürnberg
  • Brian Fowler
  • Frank Rutsch
Review

DOI: 10.1007/s00109-010-0601-x

Cite this article as:
Gailus, S., Höhne, W., Gasnier, B. et al. J Mol Med (2010) 88: 459. doi:10.1007/s00109-010-0601-x

Abstract

Vitamin B12 (cobalamin) is essential in animals and humans for metabolism of methylmalonic acid, for the remethylation of homocysteine to methionine and, consequently, for all S-adenosylmethionine-dependent methylation reactions, including DNA synthesis. In man, cobalamin deficiency leads to anemia and neurologic and cognitive impairment. In the cblF inborn error of vitamin B12 metabolism, free vitamin accumulates in lysosomes and cannot be converted to cofactors for mitochondrial methylmalonyl-CoA mutase and cytosolic methionine synthase. Recent work has shown that this defect is caused by mutations in the lysosomal membrane protein LMBD1, which shows significant homology to lipocalin membrane receptors, thereby indicating that LMBD1 is a lysosomal membrane exporter for cobalamin.

Keywords

Vitamin B12CobalamincblFMethylmalonic aciduriaHyperhomocysteinemia

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Susann Gailus
    • 1
  • Wolfgang Höhne
    • 2
  • Bruno Gasnier
    • 3
  • Peter Nürnberg
    • 4
  • Brian Fowler
    • 5
  • Frank Rutsch
    • 1
    • 6
  1. 1.Department of General PediatricsMünster University Children’s HospitalMünsterGermany
  2. 2.Department of BiochemistryCharité University Medical CenterBerlinGermany
  3. 3.Institut de Biologie Physico-Chimique, Centre National de la Recherche ScientifiqueUniversité Paris DescartesParisFrance
  4. 4.Cologne Center for Genomics, Institute for Human GeneticsUniversity of CologneCologneGermany
  5. 5.Metabolic UnitUniversity Children’s HospitalBaselSwitzerland
  6. 6.Klinik und Poliklinik für Kinder- und JugendmedizinUniversitätsklinikum MünsterMünsterGermany