Insights into lysosomal cobalamin trafficking: lessons learned from cblF disease.

Gailus, Susann; Höhne, Wolfgang; Gasnier, Bruno; Nürnberg, Peter; Fowler, Brian; Rutsch, Frank

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.

VITAMIN B12; BIOCHEMISTRY; HOMOLOGY (Biology); MEMBRANE proteins; BLOOD diseases

Journal of Molecular Medicine, 2010, Vol 88, Issue 5, p459

0946-2716

Academic Journal

10.1007/s00109-010-0601-x