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At least 19 recordsLinked to original sources
PubMed1990

Methemoglobin formation in the blood of Japanese subjects and mice suffering from acatalasemia in response to methemoglobin inducers.

Hemolysates or erythrocytes prepared from Japanese normal and acatalasemic subjects were exposed to nitrogen monoxide or nitrogen dioxide, and methemoglobin formation was determined. Concentrations of methemoglobin in human and mouse acatalasemic hemolysates exposed to nitrogen monoxide or nitrogen dioxide were higher than those in the normal hemolysates. Results similar to Japanese acatalasemic hemolysates or erythrocytes were obtained with mouse hemolysates or erythrocytes. When acatalasemic mice were exposed to nitrogen monoxide, the methemoglobin concentration in the blood was higher than that in the normal mice. Similar results on methemoglobin formation were obtained after exposing mice to nitrogen dioxide, although the rate of methemoglobin formation was lower in the blood of nitrogen dioxide-exposed mice. The methemoglobin concentration in erythrocytes of acatalasemic mice after the addition of sodium nitrite was higher than that in red cells of normal ones. Methemoglobin concentration in the blood of mice receiving sodium nitrites in vivo was determined, and found that the methemoglobin concentration in the blood of acatalasemic mice was higher than that in the blood of normal ones. These results indicated that the formation of methemoglobin from hemoglobin with nitrogen monoxide, nitrogen dioxide and nitrite ion appears to be controlled by the blood catalase.

Animals↗
PubMed1981

Properties of methemoglobin reductase and kinetic study of methemoglobin reduction.

A soluble erythrocyte cytochrome b5 was purified as the substrate of methemoglobin reductase and an electron carrier to methemoglobin. The isoelectric point of this protein was at pH 4.3, and E0' was -0.010 at pH 7.0.. The Km value of the enzyme for this protein was 1 x 10(-4) M, and the turnover number (k5) was 3.4 x 10(4) min-1, with NADH as an electron donor at pH 7.0. The optimum pH of the enzyme was pH 4.6 for ferricyanide and pH 5.5 for cytochrome b5, with a shoulder of activity at pH 7 to 9 for both substrates. The rate equation which represents the reduction of either methemoglobin or cytochrome c was obtained as a function of methemoglobin or cytochrome c, methemoglobin reductase, and cytochrome b5 by considering the E . S complex for both reductase and cytochrome b5, and the rate constants involved were determined. The rate constants between methemoglobin and reduced cytochrome b5 (k1, M-1 min-1) were 1.6 x 10(4), 3.1 x 10(6), and 4.1 x 10(6) at pH 7.0, pH 5.2, and pH 5.0, respectively. The rate constants between the reduced enzyme and oxidized cytochrome b5 (k'3, M-1 min-1) were 4.3 x 10(8), 12 x 10(8), and 9.3 x 10(8) at pH 7.0, pH 5.2, and pH 5.0, respectively. The rate constant between reduced hemoglobin and oxidized cytochrome b5 (k2) was 35 M-1 min-1 at pH 7.0. The theoretical Km for methemoglobin was 2.1 M at an infinite enzyme concentration at pH 7.0

Cytochrome-B(5) Reductase↗
PubMed1981

Interaction of methemoglobin with inositol hexaphosphate. Presence of the T state in human adult methemoglobin in the low spin state.

The interaction of human methemoglobin with inositol hexaphosphate (IHP) was examined by proton NMR spectroscopy. Upon addition of IHP, new proton peaks which are distinguishable from those observed in the absence of IHP appeared irrespective of the spin state of the ferric heme iron. the IHP-induced NMR peaks of low spin azide methemoglobin were not observed when azide was titrated to stripped aquomethemoglobin. Therefore, it was indicated that the IHP-induced peaks are not due to the slight dissociation of azide. Azide titration to aquomethemoglobin in the presence of IHP further revealed that the IHP-induced peaks are not due to a localized structural change but rather due to the presence of an IHP-induced new conformer. The NMR spectral intensity calibration for the 5-methylimidazole complex of methemoglobin showed that the intensity of the spectrum of stripped methemoglobin decreased by about 80% upon addition of IHP, suggesting the structural alterations in both of the alpha and beta subunits. The intensity of the IHP-induced peak at 31.1 ppm in azide methemoglobin spectrum decreased at both higher and lower pD values with its optimal around pD 6.7. The pD dependence of this peak was closely similar to that of the exchangeable proton NMR peak which has been used as a measure of the T quaternary conformation for human aquomethemoglobin (Huang, T.-H. (1979) J. Biol. Chem. 254, 11467-11474). From all of the above results, it was concluded that human low spin methemoglobin can be switched from the R to T quaternary structures by the binding of IHP. The allosteric constant L4 = [T4]/[R4] for the fully ligated low spin methemoglobin increased with decreasing temperature and was estimated to be 1 to 5 at room temperature.

Adult↗
PubMed1981

Interactions of solvent with the heme region of methemoglobin and fluoro-methemoglobin.

It is now more than 20 years since Davidson and collaborators (1957, Biochim. Biophys, Acta. 26:370-373; J. Mol. Biol. 1:190-191) applied the theoretical ideas of Bloembergen et al. (1948. Phys. Rev. 73:679-712) on outer sphere magnetic relaxation of solvent protons to studies of solutions of methemoglobin. From then on, there has been debate regarding the relative contributions to paramagnetic solvent proton relaxation by inner sphere (ligand-exchange) effects and by outer sphere (diffusional) effects in methemoglobin solutions. Gupta and Mildvan (1975. J. Biol. Chem 250:146-253) extended the early measurements, attributed the relatively small paramagnetic effects to exchange with solvent of the water ligand of the heme-Fe3+ ion, and interpreted their data to indicate cooperativity and an alkaline Bohr effect in the presence of inositol hexaphosphate. They neglected the earlier discussions entirely, and made no reference to outer sphere effects. We have measured the relaxation rate of solvent protons as a function of magnetic field for solutions of methemoglobin, under a variety of conditions of pH and temperature, and have given careful consideration to the relatively large diamagnetic corrections that are necessary by making analogous measurements on oxyhemoglobin, carbonmonoxyhemoglobin, and cyano- and azide-methemoglobin. (The latter two, because of their short electronic relaxation times, behave as though diamagnetic). We show that the paramagnetic contribution to solvent relaxation can be dominated by outer sphere effects, a result implying that many conclusions, including those of Gupta and Mildvan, require reexamination. Finally, we present data for fluoro-methemoglobin, which relaxes solvent protons an order of magnitude better than does methemoglobin. Here one has a startling breakdown of the dogma that has been the basis for interpreting many ligand-replacement studies; in contrast to the prevailing view that replacement of a water ligand of a protein-bound paramagnetic ion by another ligand should decrease relaxation rates, replacement of H2O by F- increases the relaxation rate drastically. The data can all be reconciled, however, with what is anticipated from knowledge of ligand interactions in the heme region.

Electron Spin Resonance Spectroscopy↗
PubMed1995

NMR relaxometric investigation on human methemoglobin and fluoromethemoglobin. An improved quantitative in vitro assay of human methemoglobin.

Longitudinal water proton relaxation rates of methemoglobin solutions show a strong dependence on temperature and pH. The increase of the relaxation rates with temperature is associated with shortened exchange lifetime of the coordinated water molecule. An accurate measurement of the relaxation rate of methemoglobin solutions thus requires careful control of the experimental temperature. This observation prompted the authors to look for an improved version of the relaxometric in vitro determination of methemoglobin. The method is based on transforming methemoglobin into the corresponding fluoromethemoglobin derivative, which shows both a higher relaxivity and a negligible dependence on temperature. The proposed method has been found to be in good agreement with data from spectrophotometric assays.

Humans↗
PubMed1977

Heterogeneity in the kinetics of oxygen binding to partially reduced human methemoglobin. A pulse-radiolysis study of oxygenated solutions of methemoglobin.

The pulse-radiolysis technique has been introduced because it permits a rapid reduction (in a few microseconds) of one heme group of the methemoglobin tetramer by hydrated electrons. The kinetics of the binding of oxygen to this particular valence intermediate (Hb3+) with one reduced alpha or beta subunit has been studied. It appears that the hydrated electrons preferentially reduce one type of subunit of methemoglobin at acid and neutral pH-values as is shown by the biphasic behaviour of Hb3+ on oxygenation. The second-order on-rate constants measured for the binding of oxygen to Hb3+ are 14 +/- 3 mM-1 ms-1 and 56 +/- 9 mM-1 ms-1, respectively. The relative contribution of the faster fraction is about 0.63 +/- 0.08 of the total oxygenation process. A comparison of the kinetic absorbance difference spectrum for the reduction of methemoglobin with the static difference spectrum of deoxyhemoglobin and methemoglobin in the Soret-region revealed a decreased absorbance of the unliganded subunit of Hb3+ at 430 nm. This fact suggests that Hb3+ is in the relaxed quaternary conformation, which is in agreement with the observed on-rate constants.

Humans↗
PubMed1991

Oxidation of chlorpromazine by methemoglobin in the presence of hydrogen peroxide. Formation of chlorpromazine radical cation and its covalent binding to methemoglobin.

The oxidation of chlorpromazine by methemoglobin plus H2O2 has been studied. The transient formation of the chlorpromazine radical cation in this reaction has been demonstrated by light absorption measurements. Under the experimental conditions complete conversion of chlorpromazine yields approximately 60% chlorpromazine sulfoxide. From studies with 3H-labeled chlorpromazine it appears that the remaining 40% is covalently bound to apohemoglobin. Upon reaction of methemoglobin with H2O2 a stable ferrylhemoglobin is formed. This ferrylhemoglobin is not the reactive species, which accepts the chlorpromazine electron, as its presence is not sufficient to induce chlorpromazine oxidation. For this the presence of H2O2 is a prerequisite. This indicates that a transient species in the formation of the stable ferrylhemoglobin is involved, whether this is a compound I analogue or a ferrylhemoglobin with a free radical on one of the apoprotein residues. Exposition of methemoglobin to H2O2 denatures hemoglobin and induces protein-heme crosslinks, as appears from changes in the visible absorption spectrum and heme retention by the protein after methyl ethyl ketone extraction. Reaction with CPZ partly protects against denaturation and crosslinking.

Chlorpromazine↗
PubMed1978

The spin-state transition of the hemochrome non-equilibrium conformation in partially reduced human methemoglobin. A pulse-radiolysis study of aqueous-methanol solutions of methemoglobin.

The effect of external parameters on the relaxation process of the hemochrome-type non-equilibrium conformation in partially reduced methemoglobin has been investigated. The relaxation of the intermediate ferrous low-spin state to the high-spin equilibrium conformation of hemoglobin appears to be facilitated particularly by protons and phosphate ions. In addition to studying the spin-state transition in aquomethemoglobin we have also studied it in complexes of the heme group in methemoglobin with fluoride, azide and cyanide anions.

Computers↗
PubMed1990

Impaired erythrocyte methemoglobin reduction in sickle cell disease: dependence of methemoglobin reduction on reduced nicotinamide adenine dinucleotide content.

We have examined aspects of methemoglobin (metHb) reduction in sickle and in thalassemic red blood cells (RBCs). NADH metHb reductase activity in sickle and thalassemic RBCs was significantly increased compared with normal RBCs. Because in vitro enzyme activity does not necessarily represent in vivo activity, we measured the rate of metHb reduction in intact RBCs. Intact thalassemic RBCs demonstrated a significantly increased rate of metHb reduction compared with normal RBCs. In contrast, intact sickle RBCs had a rate of metHb reduction that was similar to normal RBCs and significantly decreased relative to high reticulocyte RBCs of equivalent cell age. To determine the mechanism for the relative impairment of metHb reduction in sickle RBCs, we measured intraerythrocytic NADH, a cofactor in the metHb reduction reaction. Thalassemic RBCs had a significantly increased NADH content relative to normal RBCs. In contrast, sickle RBCs did not have an increase in NADH content. Furthermore, incubating normal RBCs under conditions that increase the NADH content resulted in an increased rate of metHb reduction. In contrast, conditions that decrease the NADH content in normal RBC resulted in a decreased rate of metHb reduction. These data and other results suggest that metHb reduction in intact RBCs is dependent on NADH content, and that the impaired metHb reduction rate in sickle RBCs may be a result of a lack of increase in NADH content. The dependence of metHb reduction on RBC NADH content and the ability to manipulate NADH content in vitro suggest a new strategy for decreasing oxidant damage to sickle RBCs in vivo.

Anemia, Sickle Cell↗