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1.
It was established in experimental normobaric and hypobaric hypoxia and hemic hypoxia induced by carbon monoxide poisoning that zinc compounds administered in a dose of 0.15 mA/kg have a marked prophylactic protective effect. The mechanism of action of zinc compounds consists in changes of oxygen transport blood function. It was shown that interaction of the hemoglobin molecule with zinc ion brings about an increase in Hb affinity for O2 (the left drive of the oxyhemoglobin dissociation curve), a reduction in cooperative interaction of hemoglobin subunits, and a relative decrease in hemoglobin affinity for carbon monoxide. The leading defence mechanism against hypoxic hypoxia is the left drive, the mechanism of defence against carbon monoxide protection consists in the lowering of the "hem-hem" cooperation and of the relative hemoglobin affinity for carbon monoxide. 相似文献
2.
Carbon monoxide and oxygen binding to human hemoglobin F0 总被引:1,自引:0,他引:1
E Di Cera M L Doyle M S Morgan R De Cristofaro R Landolfi B Bizzi M Castagnola S J Gill 《Biochemistry》1989,28(6):2631-2638
3.
B Seamonds J A McCray L J Parkhurst P D Smith 《The Journal of biological chemistry》1976,251(9):2579-2583
Oxygen and carbon monoxide kinetics of Glycera dibranchiata monomeric hemoglobin have been studied using laser photolysis, air flash, and stopped flow techniques. The reactions of this hemoglobin with both ligands were found to be more rapid than the corresponding reactions involving myoglobin and were also biphasic in nature, the rate constants being approximately an order of magnitude different for the fast and slow phases in each case. No pH or hemoglobin concentration dependence of the pseudo-first order rate constants was apparent between pH 6 and 9 and in the concentration range of 1.25 to 40 muM heme. Both fast and slow pseudo-first order oxygen combination rate constants varied linearly with oxygen concentration between 16 and 1300 muM. A first order slow relaxation was also noted which was linearly dependent on heme concentration and inversely dependent on oxygen concentration. This reaction has been shown to be due to a replacement of oxygen by carbon monoxide. The presence of this reaction is a result of the high affinity of Glycera monomer for carbon monoxide as shown by the partition coefficient Mr = approximately 20,000 ana an equilibrium dissociation constant of the order L = 1.1 X 10(-9) M. 相似文献
4.
The Secretion of Oxygen into the Swim-bladder of Fish : II. The simultaneous transport of carbon monoxide and oxygen
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Toadfish, Opsanus tau, L., were maintained in sea water equilibrated with gas mixtures containing a fixed proportion of oxygen and varying proportions of carbon monoxide. The swim-bladder was emptied by puncture, and, after an interval of 24 or 48 hours, the newly secreted gases were withdrawn and analyzed. Both carbon monoxide and oxygen are accumulated in the swim-bladder at tensions greater than ambient. The ratio of concentrations, carbon monoxide (secreted): carbon monoxide (administered) bears a constant relation to the ratio, oxygen (secreted): oxygen (administered). The value of the partition coefficient describing this relation is (α = 5.44). The two gases are considered to compete for a common intracellular carrier mediating their active transport. The suggestion is advanced that the intracellular oxygen carrier is a hemoglobin. Comparison of the proportions of carboxy- and oxyhemoglobin in the blood with the composition of the secreted gas proves that the secreted gases are not evolved directly from combination with blood hemoglobin. The suggestion is advanced that cellular oxygen secretion occurs in the rete mirabile: the rete may build up large oxygen tensions in the gas gland capillaries. It is suggested that the gas gland acts as a valve impeding back diffusion of gases from the swim-bladder. 相似文献
5.
The aim of this paper is to quantify the effect of small quantities of carbon monoxide on the facilitated diffusion of oxygen by haemoglobin in the steady state. It is the first phase in the study of a mathematical model for carbon monoxide poisoning. Here we extend the Wyman model for facilitated diffusion to the case in which there are two ligands. The equations are solved using an asymptotic technique developed by Murray. We obtain accurate analytic approximations for the biologically important quantities of the problem for various percentages of carbon monoxide. These are the concentrations of free oxygen, haemoglobin, oxyhaemoglobin and carboxyhaemoglobin, and hence the saturation of the protein and the facilitated oxygen flux. The major effect of very small quantities of carbon monoxide on the oxygen flux is shown. 相似文献
6.
The time-dependent theory developed in Part I is specialized to treat tetrameric hemoglobin, and the results of the theory for dimeric-and tetrameric hemoglobin are compared with data on the kinetics of the reactions of hemoglobin with carbon monoxide and oxygen at various salt concentrations for the case of large concentration of ligand relative to that of hemoglobin. The fit of the theoretical results to the data suggests that hemoglobin at a 2 M salt concentration is predominantly dimeric and that the tetramer should be taken as the functional unit to explain the kinetics of the reactions of normal hemoglobin. A relationship is established between the time-dependent theory arid Adair's Intermediate Compound Hypothesis (I.C.H.) for hemoglobin, as brought to its present state by Gibson and Roughton. A generalization (G.I.C.H.) of the I.C.H. is presented and is shown to be equivalent to the time-dependent theory in the limit of infinite ligand concentration. The I.C.H. is shown to be an excellent approximation to the centralized theory (G.I.C.H.) in this limit. 相似文献
7.
The biological functions of heme proteins are linked to their rate and affinity constants for ligand binding. Kinetic experiments are commonly used to measure equilibrium constants for traditional hemoglobins comprised of pentacoordinate ligand binding sites and simple bimolecular reaction schemes. However, kinetic methods do not always yield reliable equilibrium constants with more complex hemoglobins for which reaction mechanisms are not clearly understood. Furthermore, even where reaction mechanisms are clearly understood, it is very difficult to directly measure equilibrium constants for oxygen and carbon monoxide binding to high-affinity (K(D) < 1 micro M) hemoglobins. This work presents a method for direct measurement of equilibrium constants for high-affinity hemoglobins that utilizes a competition for ligands between the "target" protein and an array of "scavenger" hemoglobins with known affinities. This method is described for oxygen and carbon monoxide binding to two hexacoordinate hemoglobins: rice nonsymbiotic hemoglobin and Synechocystis hemoglobin. Our results demonstrate that although these proteins have different mechanisms for ligand binding, their affinities for oxygen and carbon monoxide are similar. Their large affinity constants for oxygen, 285 and approximately 100 micro M(-1) respectively, indicate that they are not capable of facilitating oxygen transport. 相似文献
8.
Carbon monoxide binding to human hemoglobin A0 总被引:3,自引:0,他引:3
The carbon monoxide binding curve to human hemoglobin A0 has been measured to high precision in experimental conditions of 600 microM heme, 0.1 M N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid, 0.1 M NaCl, 10 mM inositol hexaphosphate, 1 mM disodium ethylenediaminetetraacetic acid, pH 6.94, and 25 degrees C. Comparison to the oxygen binding curve in the same experimental conditions demonstrates that the two curves are not parallel. This result invalidates Haldane's two laws for the partitioning between carbon monoxide and oxygen to human hemoglobin. The partition coefficient is found to be 263 +/- 27 at high saturation, in agreement with previous studies, but is lowered substantially at low saturation. Although the oxygen and carbon monoxide binding curves are not parallel, both show the population of the triply ligated species to be negligible. The molecular mechanism underlying carbon monoxide binding to hemoglobin is consistent with the allosteric model [Di Cera, E., Robert, C. H., & Gill, S. J. (1987) Biochemistry 26, 4003-4008], which accounts for the negligible contribution of the triply ligated species in the oxygen binding reaction to hemoglobin [Gill, S. J., Di Cera, E., Doyle, M. L., Bishop, G. A., & Robert, C. H. (1987) Biochemistry 26, 3995-4002]. The nature of the different binding properties of carbon monoxide stems largely from the lower partition coefficient of the T state (123 +/- 34), relative to the R state (241 +/- 19).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
9.
C Bonaventura J Bonaventura B Kitto M Brunori E Antonini 《Biochimica et biophysica acta》1976,428(3):779-786
It has been established that Molpadia hemoglobin tends to dissociate into subunits as oxygen is bound. The kinetics and equilibria of carbon monoxide and ethylisocyanide binding reported here show a dependence on protein concentration that supports the conclusion that the aggregated hemoglobin has a lower ligand affinity than the dissociated subunits. This is true for the isolated D-chain as well as for the unfractionated hemolysate that contains four distinct polypeptide chains (A-D). This indicates that even homopolymers of Molpadia hemoglobin have lower ligand affinity than the dissociated subunits. At high protein concentration hemolysates of Molpadia hemoglobin show slight cooperativity. The time course of ligand binding to the deoxy D-chain also suggests cooperative interactions. The low affinity of the aggregated state may have a different molecular explanation than in human hemoglobin where tetramers of identical subunits (as in Hb H) show high oxygen affinity. The absence of tyrosine and histidine at the C-terminal of the Molpadia D-chains also suggests a different stabilization of the low affinity deoxy state. An additional functional difference between Molpadia hemoglobin and human hemoglobin is that organic phosphates do not alter the ligand affinity of the sea cucumber hemoglobin. 相似文献
10.
The distal side of the heme pocket, known to regulate ligand affinity, is shown to be directly involved in subunit interactions. Valency hybrids with oxygen or carbon monoxide bound to the reduced chain are used to model R-state hemoglobin with different distal perturbations. Electron paramagnetic resonance of the oxidized chains shows that the carbon monoxide perturbation is transmitted between subunits to the distal histidine and the oxidized iron center. A comparison of hybrids with only one type of chain oxidized and hybrids with a single alpha beta dimer oxidized is consistent with this perturbation being transmitted across the alpha 1 beta 1 interface. This represents a new mode of subunit interactions in hemoglobin. 相似文献
11.
Solutions of protohemin in aqueous buffer containing imidazole were reduced and exposed to carbon monoxide forming the carbon monoxide-imidazole complex similar to that in carboxyhemoglobin. This complex is stable for long periods in the presence of low pressures of oxygen and thus the standard flash photolysis methods can be used to determine rates of combination of the heme-imidazole complex with oxygen. Combination rates for both carbon monoxide and oxygen are faster than any on rates for hemoglobin and oxygen dissociation rates are also faster. But the equilibrium constant for binding of this isolated site is larger than that for hemoglobin. 相似文献
12.
Cliff WH 《Advances in physiology education》2006,30(4):215-223
Most students enter the physiology classroom with one or more fundamental misconceptions about respiratory physiology. This study examined the prevalence of four respiratory misconceptions and determined the role of case analysis in the remediation of one of them. A case study was used to help students learn about oxygen transport in the blood and a conceptual diagnostic test was used to assess student understanding of the relation between Po(2) and hemoglobin saturation by probing for the corresponding (Sa/Po(2)) misconception. A 36% remediation of the Sa/Po(2) misconception was found to be associated with case analysis. This repair was selective since the frequency of three other respiratory misconceptions was found to be unchanged after classroom instruction about respiratory physiology in lectures and laboratories. Remediation of the Sa/Po(2) misconception before an instructor-led, in-class case review was superficial and temporary. Explanations provided by students who correctly answered the Sa/Po(2) conceptual diagnostic test showed improved conceptual understanding following case analysis. These results suggest that a learning strategy where students actively confront their faulty notions about respiratory physiology is useful in helping them overcome their misconceptions. 相似文献
13.
14.
Stefan Bosch 《当今生物学》2016,46(2):114-117
Unexpected carbon monoxide poisonings The poisonous gas carbon monoxide (CO) is not only produced as a result of combustion processes but can also be inhaled during the operation of barbecues, the smoking of water pipes, or in wood pellet stores. Inhalation of carbon monoxide can lead to life‐threatening or chronic poisoning. The present article provides information on the formation and effects of CO in domestic settings, and gives advice on how instances of poisoning can be avoided. 相似文献
15.
A thin-layer gas-solution microcalorimeter has been developed to study the binding reactions of gaseous ligands with ligand binding macromolecules. We have measured the enthalpy of binding oxygen and carbon monoxide to horse myoglobin, human hemoglobin A0 and sperm whale myoglobin in phosphate buffer at pH 7.6, with the enzyme reducing system of Hayashi. Reactions of human hemoglobin were also done under various buffer conditions in order to elucidate the Bohr effect. These binding reactions were found not to exhibit a detectable enthalpy change over the temperature range of 10 degrees C to 25 degrees C. The enzyme reducing system was shown to react with oxygen in a manner that releases a substantial amount of heat. This problem was corrected by using a minimum amount and by placing the buffer and enzyme system in the reference cell effectively cancelling the oxygen enzyme reaction heat as well as the heat of gas dissolution. It was also demonstrated that glucose-6-phosphate, one of the reducing system components, in 50 mM concentrations can influence the heat of binding oxygen and carbon monoxide to hemoglobin. This effect was shown to be absent in the myoglobins and also with hemoglobin at glucose-6-phosphate concentrations less than 5 mM. 相似文献
16.
目的:探讨急性一氧化碳中毒(ACOP)患者的发病特点、临床表现及其对预后的影响。方法:回顾性分析2006年1月一2011年12月我院收治的131例ACOP患者,将其按病情的严重程度分为轻、中、重度3组,比较各组的发病原因和临床表现。结果:接触时间、基础疾病、血清肌酸激酶(CK)、昏迷时间在3组间差异有显著性(P〈0.01),年龄、性别、中毒原因方面3组间差异无显著性(P〉0.05)。迟发性脑病组和无迟发性脑病组在年龄、基础疾病、并发症、接触时间、昏迷时间、CK方面差异有显著性(P〈0.01);而在性别、中毒原因方面差异无显著性(P〉0.05)。结论:对于ACOP患者而言,接触时间长、伴有基础疾病、昏迷时间长、CK高不仅提示病情的严重程度,更是迟发性脑病的易患因素。而高压氧治疗是ACOP的首选及有效的治疗方法。 相似文献
17.
J B Wittenberg B A Wittenberg Q H Gibson M J Trinick C A Appleby 《The Journal of biological chemistry》1986,261(29):13624-13631
Hemoglobin I was isolated from nodules formed on the roots of Parasponia andersonii inoculated with Rhizobium strain CP 283. The rate of oxygen dissociation from Parasponia hemoglobin increases about 12-fold between pH 4 and 7, with apparent pK 6.4, to reach a limiting value of 14.8s-1. The optical spectrum of oxyhemoglobin in the visible region is also dependent on pH with pK near 6.4. The rate constant for oxygen combination with Parasponia hemoglobin increases about 7-8-fold between pH 4 and 7, with apparent pK 5.37, to reach a value of 1.67 X 10(8) M-1 s-1 at pH 7. The optical spectrum of deoxyhemoglobin in the visible region and the rate constant for carbon monoxide combination are also dependent on pH with apparent pK 5.65 and 5.75, respectively. The rate constant for carbon monoxide dissociation is independent of pH. The oxygen affinity of Parasponia hemoglobin, P50 = 0.049 torr at 20 degrees C, calculated from the kinetic constants at pH 7, is very great. At alkaline pH there is a prominent geminate reaction with oxygen and nitric oxide, with both subnanosecond and tens of nanosecond components. These reactions disappear at acid pH, with pK 6.4, and the effective quantum yield is reduced. In general, the reactions of Parasponia hemoglobin with oxygen and carbon monoxide resemble those of soybean leghemoglobin. In each, great oxygen affinity is achieved by unusually rapid oxygen combination together with a moderate rate of oxygen dissociation. We suggest that protonation of a heme-linked group with pK near 6.4 controls many properties of Parasponia oxyhemoglobin, and protonation of a group with pK near 5.5 controls many properties of Parasponia deoxyhemoglobin. 相似文献
18.
Celia Bonaventura Joseph Bonaventura Barrie Kitto Maurizio Brunori Eraldo Antonini 《Biochimica et Biophysica Acta (BBA)/General Subjects》1976,428(3):779-786
It has been established that Molpadia hemoglobin tends to dissociate into subunits as oxygen is bound. The kinetics and equilibria of carbon monoxide and ehtylisocyanide binding reported here show a dependence on protein concentration that supports the conclusions that the aggregated hemoglobin has a lower ligand affinity than the dissociated subunits. This is true for the isolated D-chain as well as for the unfractionated hemolysate that contains four distinct polypeptide chains (A-D). This indicates that even homopolymers of Molpadia hemoglobin have lower ligand affinity than the dissociated subunits. At high protein concentration hemolysates of Molpadia hemoglobin show slight cooperativity. The time course of ligand binding to the deoxy D-chain also suggests cooperative interactions, The low affinity of the aggregated state may have a different molecular explanation than in human hemoglobin were tetramers of identical subunits (as in Hb H) show high oxygen affinity. The absence of tyrosine and histidine at the C-tremini of the Molpadia D-chains also suggests a different stabilization of the low affinity deoxy state. An additional functional difference between Molpadia hemoglobin and human hemoglobin is that organic phosphate do not alter the ligand affinity of the sea cucumber hemoglobin. 相似文献
19.
The reaction of Xenopus hemoglobin with oxygen and carbon monoxide has been reinvestigated over the pH range 8.5-6.0, in the absence and presence of organic phosphates (2,3-diphosphoglycerate or inositol hexakisphosphate), to establish if the tetramer can be stabilized in a T-quaternary state by protons and polyphosphate; the equilibrium and kinetic data indicate that Xenopus hemoglobin does exhibit a Root effect. These new results are discussed with reference to those reported by Bridges et al. [(1985) Resp. Physiol. 61, 125-136] on Xenopus blood and, more generally, to the molecular definition and the structural basis of the Root effect as an extreme form of the Bohr effect. 相似文献
20.
The objective of this study was to evaluate the brain function characteristics of carbon monoxide poisoning patients using resting-state functional magnetic resonance imaging (fMRI) method. For this purpose, 12 carbon monoxide poisoning patients and healthy controls were subjected to resting-state fMRI scans separately. A regional homogeneity (ReHo) approach was used to analyze the brain function in carbon monoxide poisoning patients. Compared with control group, the value of ReHo in carbon monoxide poisoning group showed distinct decrease in bilateral superior frontal gyrus, middle frontal gyrus, right cuneus, left middle temporal gyrus, right insula, and cerebellum. Therefore, it was concluded that the brain functions in carbon monoxide poisoning patients were abnormal under the resting-state. The cuneate lobe function may indicate the degree of brain hypoxia and strengthening the cerebellar function training may promote the rehabilitation process. 相似文献