Nanosecond Absorption Study of Kinetics Associated with Carbon Monoxide Rebinding to Hemoglobin S and Hemoglobin C Following Ligand Photolysis

Shapiro, Daniel B.; Paquette, S. J.; Esquerra, Raymond M.; Che, Diping; Goldbeck, Robert A.; Hirsch, Rhoda Elison; Mohandas, Naveen; Kliger, David S.

doi:10.1006/bbrc.1994.2643

Cited by 11 publications

(10 citation statements)

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“…3 (a and b) shows that the high and low frequency regions of the resonance Raman spectra of both the equilibrium deoxy form and the 10-ns transient photoproduct of HbA and HbC are identical within our spectral resolution. Identical proximal and distal heme pocket environments would be consistent with the recent report by Shapiro et al (17) that there are no differences between HbA and HbC with respect to CO geminate recombination kinetics (10-ns resolution). Geminate rebinding has been shown to be sensitive to both proximal (18) and distal (19) perturbations.…”

Section: Resultssupporting

confidence: 91%

Conformational Changes in Oxyhemoglobin C (Gluβ6 → Lys) Detected by Spectroscopic Probing

Hirsch

Lin

Vidugirus

et al. 1996

Journal of Biological Chemistry

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Exposure of an N-terminal hydrophobic region in troponin C is thought to be important for the regulation of contraction in striated muscle. To test this hypothesis, single Cys residues were engineered at positions 45, 81, 84, or 85 in the N-terminal hydrophobic region of cardiac troponin C (cTnC) to provide specific sites for attachment of blocking groups. A synthetic peptide, Ac-Val-Arg-Ala-Ile-Gly-Lys-Leu-Ser-Ser, or biotin was coupled to these Cys residues, and the covalent adducts were tested for activity in TnC-extracted myofibrils. Covalent modification of cTnC(C45) had no effect on maximal myofibril ATPase activity. Greatly decreased myofibril ATPase activity (70-80% inhibited) resulted when the peptide was conjugated to Cys-81 in cTnC(C81), while a lesser degree of inhibition (10-25% inhibited) resulted from covalent modification of cTnC(C84) and cTnC(C85). Inhibition was not due to an altered affinity of the cTnC(C81)/peptide conjugate for the myofibrils, and the Ca2+ dependence of ATPase activity was essentially identical to the unmodified protein. Thus, a subregion of the N-terminal hydrophobic region in cTnC is sensitive to disruption, while other regions are less important or can adapt to rather bulky blocking groups. The data suggest that Ca(2+)-sensitizing drugs may bind to the N-terminal hydrophobic region on cTnC but not interfere with transmission of the Ca2+ signal.

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Section: Resultssupporting

confidence: 91%

Conformational Changes in Oxyhemoglobin C (Gluβ6 → Lys) Detected by Spectroscopic Probing

Hirsch

Lin

Vidugirus

et al. 1996

Journal of Biological Chemistry

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“…In another study, the rate that deoxygenated normal adult hemoglobin, HbA 0 , reacts with nitrite was compared with the rate that sickle cell hemoglobin, HbS, reacts with nitrite. 22 The ligand affinity of solution phase (unpolymerized) HbS is the same as HbA 0 , [28][29][30][31] so that any differences in the nitrite-deoxyhemoglobin reaction between these hemoglobin variants could be due to redox potential (note that we cannot exclude unknown differences in nitrite binding that are different from oxygen binding). The redox potential of HbS is lower than HbA 0 .…”

Section: Redox Potential and Ligand Accessibilitymentioning

confidence: 99%

The functional nitrite reductase activity of the heme-globins

Gladwin

Kim‐Shapiro

2008

Blood

259

195

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Hemoglobin and myoglobin are among the most extensively studied proteins, and nitrite is one of the most studied small molecules. Recently, multiple physiologic studies have surprisingly revealed that nitrite represents a biologic reservoir of NO that can regulate hypoxic vasodilation, cellular respiration, and signaling. These studies suggest a vital role for deoxyhemoglobin-and deoxymyoglobindependent nitrite reduction. Biophysical and chemical analysis of the nitritedeoxyhemoglobin reaction has revealed unexpected chemistries between nitrite and deoxyhemoglobin that may contribute to and facilitate hypoxic NO generation and signaling. The first is that hemoglobin is an allosterically regulated nitrite reductase, such that oxygen binding increases the rate of nitrite conversion to NO, a process termed R-state catalysis. The second chemical property is oxidative denitrosylation, a process by which the NO formed in the deoxyhemoglobinnitrite reaction that binds to other deoxyhemes can be released due to heme oxidation, releasing free NO. Third, the reaction undergoes a nitrite reductase/anhydrase redox cycle that catalyzes the anaerobic conversion of 2 molecules of nitrite into dinitrogen trioxide (N 2 O 3 ), an uncharged molecule that may be exported from the erythrocyte. We will review these reactions in the biologic framework of hypoxic signaling in blood and the heart. IntroductionNitric oxide (NO) is a diatomic gas molecule that is a critical regulator of basal blood vessel tone and vascular homeostasis (antiplatelet activity, modulation of endothelial and smooth muscle proliferation, and adhesion molecule expression). [1][2][3][4][5] NO is a paracrine signaling molecule, as it is produced in endothelium and then diffuses to vicinal smooth muscle to activate soluble guanylyl cyclase that produces cGMP, and ultimately produces smooth muscle relaxation. Nitric oxide is subject to rapid inactivation reactions with hemoglobin that greatly limit its lifetime in blood, however recent studies suggest that NO formed from endothelial NO synthases is also oxidized by oxygen or plasma ceruloplasmin to form nitrite. 6 Nitrite transport in blood provides an endocrine form of NO that is shuttled from the lungs to the periphery, while limiting the exposure of authentic NO to the scavenging red cell environment. Then during the rapid hemoglobin deoxygenation from artery to vein the nitrite is reduced back to NO. Such a cycle conserves NO in the one electron oxidation state. In this model, the nitrite pool represents the "live payload," only one electron away from NO.We have hypothesized that nitrite and the heme-globin family subserve a critical NO signaling function in blood, smooth muscle cells, the cardiomyocyte, and skeletal muscle cells. In these environments, NO is conserved by oxidation, allowing nitrite storage and free nitrite diffusion. As oxygen tensions decrease, nitrite reactions with deoxygenated hemoglobin, myoglobin, neuroglobin, cytoglobin, and other heme proteins may generate NO to regulate physiologic h...

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“…Such data include, for example, the number of intermediates present in a reaction, the rate or equilibrium constants, and the spectra for each one of those intermediates [40][41][42]. For example, singular value decomposition (SVD) and global analysis were used to determine the kinetics of the binding of the CO to the HbS polymers that was recorded by time resolved optical spectroscopy, then results were compared with CO-deoxy HbA complex [43], or to determine the re-equilibration rate of carbon monoxide binding to HbS polymers is determined by time-resolved measurements of linear dichroism spectra [44]. Multivariate curve resolutionalternating least squares (MCR-ALS) [45] is a well-known resolution methodology that has been used to model processes [46][47][48].…”

Section: Introductionmentioning

confidence: 99%

Comparison between two different hemichromes of hemoglobins (HbA and HbS) induced by n-dodecyl trimethylammonium bromide: Chemometric study

Mojtahedi

Parastar

Jalali‐Heravi

et al. 2008

Colloids and Surfaces B: Biointerfaces

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Nanosecond Absorption Study of Kinetics Associated with Carbon Monoxide Rebinding to Hemoglobin S and Hemoglobin C Following Ligand Photolysis

Cited by 11 publications

References 0 publications

Conformational Changes in Oxyhemoglobin C (Gluβ6 → Lys) Detected by Spectroscopic Probing

Conformational Changes in Oxyhemoglobin C (Gluβ6 → Lys) Detected by Spectroscopic Probing

The functional nitrite reductase activity of the heme-globins

Comparison between two different hemichromes of hemoglobins (HbA and HbS) induced by n-dodecyl trimethylammonium bromide: Chemometric study

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