Insights into lysosomal cobalamin trafficking: lessons learned from cblF disease

J Mol Med (Berl). 2010 May;88(5):459-66. doi: 10.1007/s00109-010-0601-x. Epub 2010 Feb 20.

Abstract

Vitamin B(12) (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 B(12) 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Humans
  • Lysosomal Membrane Proteins / genetics*
  • Lysosomes / metabolism*
  • Metabolism, Inborn Errors / genetics
  • Metabolism, Inborn Errors / metabolism*
  • Molecular Sequence Data
  • Nucleocytoplasmic Transport Proteins / genetics
  • Sequence Alignment
  • Vitamin B 12 / metabolism*

Substances

  • LMBRD1 protein, human
  • Lysosomal Membrane Proteins
  • Nucleocytoplasmic Transport Proteins
  • Vitamin B 12