PubMed Health⌕ Search

Biomedical subjects

I Tyuma

Publications and source records attributed to I Tyuma.

13 recordsLinked to original sources
PubMed1989

The interaction between nitrogen oxides and hemoglobin and endothelium-derived relaxing factor.

Among nitrogen oxides, NO and NO2 are free radicals and show a variety of biological effects. NO2 is a strongly oxidizing toxicant, although NO, not oxidizing as NO2, is toxic in that it interacts with hemoglobin to form nitrosyl- and methemoglobin. Nitrosylhemoglobin shows a characteristic electron spin resonance (ESR) signal due to an odd electron localized on the nitrogen atom of NO and reacts with oxygen to yield nitrate and methemoglobin, which is rapidly reduced by methemoglobin reductase in red cells. NO was found to inhibit the reductase activity. Part of NO inhaled in the body is oxidized by oxygen to NO2, which easily dissolves in water and converts to nitrite and nitrate. The nitrite oxidizes oxyhemoglobin autocatalytically after a lag. The mechanism of the oxidation, particularly the involvement of superoxide, was controversial. The stoichiometry of the reaction has now been established using nitrate ion electrode and a methemoglobin free radical was detected by ESR during the oxidation. Complete inhibition of the autocatalysis by aniline or aminopyrine suggests that the radical catalyzes conversion of nitrite to NO2, which oxidizes oxyhemoglobin. Recently NO was shown to be one of endothelium-derived relaxing factors and the relaxation induced by the factor was inhibited by hemoglobin and potentiated by superoxide dismutase.

Free Radicals↗
PubMed1989

Spectrophotometric, electron paramagnetic resonance and oxygen binding studies on the hemoglobin from the marine polychaete Perinereis aibuhitensis (Grübe): comparative physiology of hemoglobin.

The physicochemical properties of giant hemoglobin (Hb) of the marine polychaete Perinereis aibuhitensis were extensively studied and the following results were obtained. (1) Light absorption spectra of the oxy, deoxy, CO, met, and cyanomet derivatives were similar to those for human Hb, except for a somewhat peculiar shape and pH-dependence of the met derivative, and high absorbance values around 277 nm for all these derivatives of Perinereis Hb. Abnormal pH dependence for the met derivative was confirmed by powder electron parmagnetic resonance (EPR) spectroscopy, which revealed that a water molecule does not coordinate to the heme iron as a sixth ligand. The high absorption around 277 nm is indicative of the existence of some non-heme polypeptide chains and/or a high content of aromatic residues in the molecule. (2) UV difference and derivative spectra revealed oxygenation-induced conformational changes in the protein moiety that are related to the degree of cooperativity. (3) The EPR spectrum for the nitrosyl derivative showed well-resolved triplet-triplet splittings due to 14N, indicating that the proximal residue is probably a histidine. (4) The oxygen affinity and cooperativity of this Hb were pH-dependent. Mg2+ markedly increased the oxygen affinity, the Bohr effect, and the cooperativity, which was maximal at physiological pH. CO2 and anions such as 2,3-diphosphoglycerate and inositol hexaphosphate had no effect on the oxygenation properties. Thus, different from vertebrate Hb, the oxygen-binding properties of this Hb are regulated by divalent cations which bind preferentially to the oxy form. The low temperature-dependence of oxygen affinity observed for this Hb is a sign of adaptation to the environment by this poikilothermic organism. (5) By using a graphic method, the minimal functional unit that preserves the full cooperativity (allosteric unit) was inferred to be the one containing 6 heme groups and its significance is discussed in connection with the structural hierarchy of the molecule.

2,3-Diphosphoglycerate↗
PubMed1987

Mechanism of autocatalytic oxidation of oxyhemoglobin by nitrite.

Oxidation of oxyhemoglobin by nitrite is characterized by the presence of a lag phase followed by autocatalysis. The stoichiometry of the overall reaction is described by the following equation: 4HbO2 + 4NO2- + 4H+ = 4Hb+ + 4NO3- + O2 + 2H2O (Hb denotes hemoglobin monomer). During the oxidation, we detected a free radical at g = 2.005, which is very similar to the methemoglobin free radical generated by the reaction with hydrogen peroxide. Nitrosylhemoglobin was not detected. The oxidation was delayed by the addition of KCN or catalase, but was not modified by superoxide dismutase in phosphate buffer. In bistris buffer, however, superoxide dimutase markedly prolonged the lag phase. The results suggest that during the oxidation, the methemoglobin peroxide compound is generated and converts nitrite into nitrogen dioxide by its peroxidatic activity. Nitrogen dioxide oxidizes oxyhemoglobin to methemoglobin and nitrite, yielding the autocatalytic phase.

Electron Spin Resonance Spectroscopy↗
PubMed1979

Influence of steric factors on oxygen binding. I. Studies on 2,4-diisopropyldeuteroheme-myoglobin.

Sperm whale apomyoglobin was recombined with 2,4-diisopropyldeuterohemin to form 2,4-diisopropyldeuteroheme-myoglobin and its various physico-chemical properties were investigated to get an insight into the structural and functional role of the peripheral vinyl groups. 2,4-Diisopropyldeuteroheme-myoglobin showed a four times lower oxygen affinity at 25 degrees C and larger enthalpy and entropy changes of oxygenation than the corresponding values of native myoglobin. 2,4-Diisopropyldeuteroheme-metmyoglobin shows a pKa value of 9.68 which is higher than those of native metmyoglobin and mesoheme-metmyoglobin. The rate of autooxidation of oxy-form was about seven times larger in 2,4-diisopropyldeuteroheme-myoglobin than in native myoglobin. The electron-donating effect of isopropyl groups does not give straightforward explanation for these anomalous properties of 2,4-diisopropyldeuteroheme-myoglobin. It is proposed that site and stereospecific van der Waals' interaction between the polypeptide side chains and the peripheral 2,4-diisopropyl groups may weaken the interaction between the bound oxygen molecule and the distal His, resulting in the decrease in the stability of oxyform.

Animals↗
PubMed1979

Stoichiometry of the reaction of oxyhemoglobin with nitrite.

During the reaction of oxyhemoglobin (HbO2) with nitrite, the concentration of residual nitrite, nitrate, oxygen, and methemoglobin (Hb+) was determined successively. The results obtained at various pH values indicate the following stoichiometry for the overall reaction: 4HbO2 + 4NO2- 4H+ leads to 4Hb+ + 4NO3- + O2 + 2H2 O (Hb denotes hemoglobin monomer). NO2- binds with methemoglobin noncooperatively with a binding constant of 340 M-1 at pH 7.4 and 25 degrees C. Thus, the major part of Hb+ produced is aquomethemoglobin, not methemoglobin nitrite, when less than 2 equivalents of nitrite is used for the oxidation.

Hemoglobin A↗
PubMed1979

The linkage between the four-step binding of oxygen and the binding of heterotropic anionic ligands in hemoglobin.

The linkage between the four-step binding of oxygen and the binding of heterotropic anionic ligands in hemoglobin was investigated by accurately measuring and analyzing the oxygen equilibrium curves of human adult hemoglobin in the presence and absence of various concentrations of one or two of the following materials: chloride (Cl-), 2,3-diphosphoglycerate (DPG), and inositol hexaphosphate (IHP). Each equilibrium curve was analyzed according to the Adair equation to evaluate the four-step oxygen equilibrium constants (Adair constants) and the median oxygen pressure. The binding constants of the anions for the molecular species of hemoglobin carrying j oxygen molecules, Hb(O2)j(j=0,1,...,4), were evaluated from the dependences of the Adair constants and the median oxygen pressure on the anion concentration by introducing a model which takes the competitive binding of Cl- and DPG or IHP into account. Assumptions made in the model are: (a) the hemoglobin molecule has two oxygen-linked binding sites for Cl- which are equivalent and independent and (b) no Cl- can be bound to hemoglobin to which DPG or IHP is already bound and vice versa. Thus, we could obtain values for the intrinsic binding constants of Cl- and DPG, i.e., the constants in the absence of other competitive anions. For IHP, only the binding constants and apparent binding constants for Hb and Hb(O2)2 were obtained. Values of the Cl- binding constants and apparent binding constants for DPG and IHP, i.e., the binding constants in the presence of Cl- for Hb and Hb(O2)4, were in reasonable agreement with literature values. From the binding constants we calculated anion binding curves for Hb(O2)j(J=0,1,...,4), the number of anions bound to Hb(O2)J, And the relationship between fractional anion saturation of hemoglobin and fractional oxygen saturation. The numbers of released anions are not uniform with respect to oxygenation step. This non-uniformity is the reason for the changes in the shape of the oxygen equilibrium curve with anion concentration changes and for the non-uniform dependences of the Adair constants on anion concentration, and also results in non-linear relations between anion saturation and oxygen saturation. The anion binding constants and various binding properties of the anions derived from those constants are consistent with those observed by other investigators using different techniques, indicating that the present model describes the oxygen-linked competitive anion binding well.

Adult↗
PubMed1978

On the validity of the spectrophotometric determination of oxygen saturation of hemoglobin. The wavelength dependence of observed oxygen equilibrium parameter values.

Spectral changes of oxyhemoglobin induced by such anions as 2,3-diphosphoglycerate, inositol hexaphosphate, and Cl- may affect the validity of the spectrophotometric determination of oxygen saturation of hemoglobin. Therefore, the anion-induced difference spectra were extensively measured under a variety of conditions and accurate oxygen equilibrium curves were determined under representative conditions with detection at different wavelengths selected from peaks, troughs, and zero difference points of the difference spectra in the visible and Soret regions. Oxygen equilibrium parameters including the four Adair constants (i.e., equilibrium constants for four steps of oxygenation) estimated from the equilibrium curves did not show any dependence on wavelength within the limits of experimental error. These results indicate that anion-induced spectral changes do not invalidate the spectrophotometric determination of oxygen saturation and confirm the validity of the previous conclusions drawn in our series of studies on the effects of anions, pH and temperature on oxygen equilibrium parameters.

Diphosphoglyceric Acids↗
PubMed1977

Evaluation of severinghaus' equation and its modification for 2, 3-dpg.

Severinghaus' equation can safely be used for the indirect estimation of oxygen half saturation pressure (P50) on the basis of blood gas parameters in normal subjects. However, 139 blood samples from 65 patients with severe injuries, the estimated P50 values differed significantly from directly measured values. The difference is highly correlated to the molar ratio of 2, 3-diphosphoglycerate to hemoglobin tetramer (2, 3-DPG ratio, [DPG]). Using this correlation, a modified Severinghaus' equation, including 2, 3-DPG molar ratio, was derived: i.e.,deltalog Po2 equals +0.48 (7.4-pH)+0.024 (T-37), +0.0013BE+0.135[DPG]-0.116 where deltalog Po2 is the shift from the standard oxygen dissociation curve, pH is plasma pH, and T and BE refer to temperature and base excess of blood, respectively. The modified equation enables one to indirectly estimate Po2 and oxygen saturation with an accuracy of plus or minus 2.5 mmHg and plus or minus 5 percent, respectively, based on blood gas parameters and 2, 3-DPG molar ratio in most clinical cases. The limitations of the equation was discussed.

Diphosphoglyceric Acids↗
PubMed1976

Effect of carbon monoxide on equilibrium between oxygen and hemoglobin.

Oxygen dissociation curves of partially CO-saturated human whole blood drawn freshly or preserved more than 3 wk were studied. With increasing CO-hemoglobin concentrations, oxygen affinity of the blood increased and the Hill coefficient, n, fell and gradually approached unity. The changes induced by CO-hemoglobin showed practically no difference in the presence or absence of 2,3-diphosphoglycerate. The Bohr coefficient, deltalog P50/deltapH, was determined as a function of oxygen saturation for various concentrations of CO-hemoglobin. The coefficient remained essentially unchanged in the presence of CO-hemoglobin. In the presence of less than 50% CO-hemoglobin, a good agreement was observed between the observed oxygen dissociation curves and the curves calculated according to Roughton and Darling (Am. J. Physiol. 141: 17-31, 1944). Based on these results, physiological implications of carboxyhemoglobinemia are discussed quantitatively in comparison with methemoglobinemia.

Carboxyhemoglobin↗