The preparation of a novel complex, ferric bromopyruvate, is described. In solutions from which most of the carbonate has been removed, ferric bromopyruvate can be used both as an iron and pyruvate source for the full iron saturation of apotransferrin. Using ferric bromopyruvate as an iron donor, iron incorporation into human apotransferrin is biphasic; the N-terminal domain is saturated three times faster than its homologous C-terminal iron binding site. Following the reaction of apotransferrin with ferric bromopyruvate, 4 moles of pyruvate per mole of transferrin are covalently bound. Based on the effect of acetylation on pyruvate and iron binding, it is suggested that lysyl residues could be the target of pyruvate bonding. However, the reaction of pyruvate with other positively charged amino acid residues cannot be excluded. The possible sites of pyruvate binding within the N-terminal domain of human serum transferrin are discussed. Covalent attachment of pyruvate to cationic amino acid residues decreased both in vitro and in vivo iron release, preferentially from the N-terminal domain of transferrin. The decreased rate of iron incorporation from iron-pyruvate-transferrin complexes by rabbit reticulocytes caused a lower iron incorporation into heme. It is suggested that an impairment of iron release from transferrin may decrease the rate of heme synthesis in reticulocytes. In vitro studies on the iron removal from iron-pyruvate-transferrin complexes showed that pyrophosphate can remove iron from this complex at an acid pH to a similar extent to the cellular mediated iron release from this complex. Based on this data, a model for the intravesicular iron release from transferrin is proposed.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.74529 |
| Date | January 1990 |
| Creators | Pulido-Cejudo, Gabriel |
| 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 | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001114799, proquestno: AAINN66352, Theses scanned by UMI/ProQuest. |
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