An investigation of hemopexin redox properties by spectroelectrochemistry: biological relevance for heme uptake
- 22 August 2007
- journal article
- Published by Springer Science and Business Media LLC in BioMetals
- Vol. 21 (3), 239-248
- https://doi.org/10.1007/s10534-007-9112-9
Abstract
Hemopexin (HPX) has two principal roles: it sequesters free heme in vivo for the purpose of preventing the toxic effects of this moiety, which is largely due to heme's ability to catalyze free radical formation, and it transports heme intracellularly thus limiting its availability as an iron source for pathogens. Spectroelectrochemistry was used to determine the redox potential for heme and meso-heme (mH) when bound by HPX. At pH 7.2, the heme-HPX assembly exhibits E (1/2) values in the range 45-90 mV and the mH-HPX assembly in the range 5-55 mV, depending on environmental electrolyte identity. The E (1/2) value exhibits a 100 mV positive shift with a change in pH from 7.2 to 5.5 for mH-HPX, suggesting a single proton dependent equilibrium. The E (1/2) values for heme-HPX are more positive in the presence of NaCl than KCl indicating that Na(+), as well as low pH (5.5) stabilizes ferro-heme-HPX. Furthermore, comparing KCl with K(2)HPO(4), the chloride salt containing system has a lower potential, indicating that heme-HPX is easier to oxidize. These physical properties related to ferri-/ferro-heme reduction are both structurally and biologically relevant for heme release from HPX for transport and regulation of heme oxygenase expression. Consistent with this, when the acidification of endosomes is prevented by bafilomycin then heme oxygenase-1 induction by heme-HPX no longer occurs.Keywords
This publication has 46 references indexed in Scilit:
- Hemoglobin and heme scavengingIUBMB Life, 2005
- Redox Properties of Human Transferrin Bound to Its ReceptorBiochemistry, 2003
- Cell-Surface NAD(P)H-Oxidase: Relationship to Trans-Plasma Membrane NADH-Oxidoreductase and a Potential Source of Circulating NADH-OxidaseAntioxidants and Redox Signaling, 2000
- The crystal structure of HasA, a hemophore secreted by Serratia marcescens.Nature Structural & Molecular Biology, 1999
- Molecular aspects of the endocytic pathwayBiochemical Journal, 1998
- Iron and copper transport in yeast and its relevance to human diseaseTrends in Biochemical Sciences, 1998
- Trans-plasma membrane electron transport: A cellular assay for NADH- and NADPH-oxidase based on extracellular, superoxide-mediated reduction of the sulfonated tetrazolium salt WST-1Protoplasma, 1998
- MCD, EPR and NMR spectroscopic studies of rabbit hemopexin and its heme binding domainBiochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1995
- Hepatic subcellular metabolism of heme from heme-hemopexin: Incorporation of iron into ferritinBiochemical and Biophysical Research Communications, 1979
- A Spectroscopic Study of the Haemin–Human‐Serum‐Albumin SystemJBIC Journal of Biological Inorganic Chemistry, 1974