Abstract
Inborn errors of vitamin B12 metabolism affect the synthesis of only Ado-B12 (Cbl A and Cbl B), total vitamin B12 accumulation and the synthesis of both Ado-Bl2 and CH3-B12 (Cbl C and Cbl D) or the synthesis of only CH3-B12 (Cbl E). It is known that after transcobalamin II (TCII)-B12 binds to specific receptors on the plasma membrane, the complex is internalized by means of adsorptive endocytosis, following which the endocytic vesicle fuses with a lysosome, and the TCII is degraded by lysosomal proteases releasing free B12 which exits the lysosome. Fibroblasts from a patient with minimal methylmalonic aciduria accumulated normal total vitamin B12 but only unbound CN-B12 when incubated in TCII-[57Co]-CN-B12. In contrast to control fibroblasts virtually all of the B12 was found in the lysosomal fraction of the cells. Treatment of the cells with chloroquine resulted in the accumulation of TCII-bound B12, in the lysosomal fraction in both control and mutant fibroblasts. These data suggest that fibroblasts from this patient are able to endocytose TCII-B12 and to release the B12 from TCII in the lysosome. Because the mutant cells do not allow the B12 to efflux across the lysosomal membrane, they accumulate neither Ado-B12 nor CH3-B12. The defect thus appears to involve vitamin B12 transport across the lysosomal membrane.
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Rosenblatt, D., Pottier, A., Matiaszuk, N. et al. 853 METHYLMALONIC ACIDURIA ASSOCIATED WITH FAILURE OF LYSOSOMAL RELEASE OF VITAMIN B12. Pediatr Res 19, 253 (1985). https://doi.org/10.1203/00006450-198504000-00883
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DOI: https://doi.org/10.1203/00006450-198504000-00883