Vitamin B12 (cobalamin, Cbl) is required as a cofactor for two human enzymes: methylmalonyl-CoA mutase (MCM) and methionine synthase (MS). Fibroblasts from patients with inborn errors of cobalamin metabolism have been classified into nine distinct complementation classes ( cblA-cblH and mut). Previous studies have shown that cobalamin binds MCM in mitochondria and MS in the cytosol. Cobalamin binding patterns were analyzed in crude mitochondrial fractions obtained from normal and mutant fibroblasts. Crude mitochondrial fractions from wildtype fibroblasts confirmed that the majority of [57Co]Cbl eluted with MCM. However, in six of the nine disorders, at least one previously unidentified mitochondrial cobalamin binding protein was observed to bind [57Co]Cbl. The proportion of [57Co]Cbl that binds, is increased when a deficiency in either adenosylcobalamin synthesis or utilization prevents binding to MCM. Furthermore, unique cobalamin binding profiles emerged, demonstrating how known mutations in these patients affect cobalamin binding to accessory proteins.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.97972 |
| Date | January 2006 |
| Creators | Moras, Emily. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Human Genetics.) |
| Rights | © Emily Moras, 2006 |
| Relation | alephsysno: 002487450, proquestno: AAIMR24746, Theses scanned by UMI/ProQuest. |
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