An investigation of hemopexin redox properties by spectroelectrochemistry: biological relevance for heme uptake |
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Authors: | Meghan M Flaherty Kimberley R Rish Ann Smith Alvin L Crumbliss |
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Institution: | (1) Department of Chemistry, Duke University, Box 90346, Durham, NC 27708-0346, USA;(2) Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri – K.C., Kansas City, MO 64110-2499, USA |
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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 K2HPO4, 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. |
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Keywords: | Heme Meso-heme Hemopexin Iron Hemophore Heme transport Redox Endocytosis |
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