Studies on carbon monoxide binding by shark haemoglobin.
Ontology highlight
ABSTRACT:
SUBMITTER: Dickinson FM
PROVIDER: S-EPMC1163144 | biostudies-other | 1981 Aug
REPOSITORIES: biostudies-other
Similar Datasets
Project description:The dimeric haemoglobin in the tracheal cells of the Gastrophilus larva was extracted and purified, and the spectral properties of its oxy- and carbon monoxide adducts are recorded. In dilute solutions the kinetic parameters of binding of oxygen and carbon monoxide were determined. In solutions between 0.1 and 50mum for oxygen k(on) is 1x10(7)m(-1).s(-1) and k(off) is 1s(-1); for carbon monoxide l(on) is 6.5x10(5)m(-1).s(-1) and l(off) is 0.14s(-1). These values are in agreement with previous equilibrium results on oxygen binding and carbon monoxide/oxygen partition. These results are discussed and compared with the known values for other monomeric protohaem proteins.
| S-EPMC1174234 | biostudies-other
Project description:Haemoglobin (Hb) is a tetrameric iron-containing protein that carries oxygen from the lungs to tissues and carbon dioxide from tissues back to the lungs. Pisces are the advanced aquatic vertebrates capable of surviving at wide depth ranges. The shortfin mako shark (SMS) is the pelagic, largest, fastest and most sophisticated species of the shark kingdom with well developed eyes. Mostly the pisces species are cold blooded in nature. Distinctly, the SMSs are warm-blooded animals with an advanced circulatory system. SMSs are capable of maintaining elevated muscle temperatures up to 33 K above the ambient water temperatures at a depth of 150-500 m. SMSs have a diverged air-breathing mechanism compared with other vertebrates. The haemoglobin molecule consists of four polypeptide chains, namely two ? chains, each with 140 amino acids and two ? chains each having 136 amino acids. The SMS Hb was found to crystallize in monoclinic space group P21 using the hanging-drop vapour-diffusion method at room temperature. The crystal packing parameters for the SMS Hb structure contain one whole biological molecule in the asymmetric unit with a solvent content of 47%. The SMS Hb quaternary structural features interface-interface interactions and heme binding sites are discussed with different state Hbs and the results reveal that SMS Hb adopts an unliganded deoxy T state conformation.
| S-EPMC3795541 | biostudies-literature
Project description:Cystathionine beta-synthase (CBS) condenses homocysteine, a toxic metabolite, with serine in a pyridoxal phosphate-dependent reaction. It also contains a heme cofactor to which carbon monoxide (CO) or nitric oxide can bind, resulting in enzyme inhibition. To understand the mechanism of this regulation, we have investigated the equilibria and kinetics of CO binding to the highly active catalytic core of CBS, which is dimeric. CBS exhibits strong anticooperativity in CO binding with successive association constants of 0.24 and 0.02 microm(-1). Stopped flow measurements reveal slow CO association (0.0166 s(-1)) limited by dissociation of the endogenous ligand, Cys-52. Rebinding of CO and of Cys-52 following CO photodissociation were independently monitored via time-resolved resonance Raman spectroscopy. The Cys-52 rebinding rate, 4000 s(-1), is essentially unchanged between pH 7.6 and 10.5, indicating that the pK(a) of Cys-52 is shifted below pH 7.6. This effect is attributed to the nearby Arg-266 residue, which is proposed to form a salt bridge with the dissociated Cys-52, thereby inhibiting its protonation and slowing rebinding to the Fe. This salt bridge suggests a pathway for enzyme inactivation upon CO binding, because Arg-266 is located on a helix that connects the heme and pyridoxal phosphate cofactor domains.
| S-EPMC2745537 | biostudies-literature
Project description:BACKGROUND:Anemia is common in liver cirrhosis. This generally infers a fall in total hemoglobin mass (tHb-mass). However, hemoglobin concentration ([Hb]) may fall due to an expansion in plasma volume (PV). The "optimized carbon monoxide rebreathing method" (oCOR) measures tHb-mass directly and PV (indirectly using hematocrit). It relies upon carboxyhemoglobin (COHb) distribution throughout the entire circulation. In healthy subjects, such distribution is complete within 6-8 min. Given the altered circulatory dynamics in cirrhosis, we sought in this pilot study, to assess whether this was true in cirrhosis. The primary aim was to ascertain if the standard timings for the oCOR were applicable to patients with chronic liver disease and cirrhosis. The secondary aim was to explore the applicability of standard CO dosing methodologies to this patient population. METHODS:Sixteen patients with chronic liver parenchymal disease were studied. However, tHb-mass was determined using the standard oCOR technique before elective paracentesis. Three subjects had an inadequate COHb% rise. In the remaining 13 (11 male), mean ± standard deviation (SD) age was 52 ± 13.8 years, body mass 79.1 ± 11.4 kg, height 175 ± 6.8 cm. To these, mean ± SD dose of carbon monoxide (CO) gas administered was 0.73 ± 0.13 ml/kg COHb values at baseline, 6 and 8 min (and "7-min value") were compared to those at 10, 12, 15 and 20 min after CO rebreathing. RESULTS:The "7-min value" for median COHb% (IQR) of 6.30% (6.21%-7.47%) did not differ significantly from those at subsequent time points (8 min: 6.30% (6.21%-7.47%), 10 min: 6.33% (6.00%-7.50%), 12 min: 6.33% (5.90%-7.40%), 15 min: 6.37% (5.80%-7.33%), 20 min: 6.27% (5.70%-7.20%)). Mean difference in calculated tHb-mass between minute 7 and minute 20 was only 4.1 g, or 0.6%, p = .68. No subjects reported any adverse effects. CONCLUSIONS:The oCOR method can be safely used to measure tHb-mass in patients with chronic liver disease and ascites, without adjustment of blood sample timings. Further work might refine and validate appropriate dosing regimens.
| S-EPMC7090373 | biostudies-literature
Project description:The CO complex of sulphaemoglobin was found to be photolytically dissociable at pH 6.0 and pH 8.5. The recombination kinetics of the CO complex after flash photolysis show two phases, which differ in rate by approximately 20-fold. At both pH 6.0 and pH 8.5 the two phases show an identical linear dependence on CO concentration, with associated second-order rate constants of 6.0 x 10(3) M-1 . s-1 and 1.2 x 10(5) M-1 . s-1 respectively. The percentage contribution of each of the two phases to the total absorbance change is independent of the CO concentration employed, but is a function of the protein concentration used. The percentage of the faster phase increases with protein dilution. These results taken together with computer simulation suggest the existence of appreciable amounts of monomeric species in solution at both pH 6.0 and pH 8.5 at low concentration of liganded protein. Estimates of the dissociation constants for the dimer in equilibrium monomer equilibrium yield values of 8 microM and 3.5 microM at pH 6.0 and pH 8.5 respectively. Stopped-flow delayed-flash-photolysis studies show that the liganded dimer decays to the liganded monomer with a half-life of approx. 0.5 s. Constant-illumination experiments allow an estimation of the half-life for the combination of deoxy monomers to deoxy dimers of 22 s. A model explaining the range of CO recombination kinetics seen for sulphaemoglobin does not require the existence of a photolytically produced high-activity form, even at high pH, in contrast with the case for normal haemoglobin.
| S-EPMC1163620 | biostudies-other
Project description:Carbon monoxide (CO) is the leading cause of poisoning deaths in many countries, including Japan. Annually, CO poisoning claims about 2000-5000 lives in Japan, which is over half of the total number of poisoning deaths. This paper discusses the physicochemical properties of CO and the toxicological evaluation of CO poisoning.
| S-EPMC6992844 | biostudies-literature
Project description: Not available
| S-EPMC4016057 | biostudies-literature
Project description:Analysis of pathways regulated by low-dose CO at the mRNA expression levels in two human breast cancer cell lines.
2022-10-21 | GSE173986 | GEO
Project description:1. Three modified horse haemoglobins have been prepared: (i) alpha(c) (2)beta(c) (2), in which both the alpha-amino groups of the alpha- and beta-chains have reacted with cyanate, (ii) alpha(c) (2)beta(2), in which the alpha-amino groups of the alpha-chains have reacted with cyanate, and (iii) alpha(2)beta(c) (2), in which the two alpha-amino groups of the beta-chain have reacted with cyanate. 2. The values of n (the Hill constant) for alpha(c) (2)beta(c) (2), alpha(2)beta(c) (2) and alpha(c) (2)beta(2) were (respectively) 2.5, 2.0 and 2.6, indicating the presence of co-operative interactions between the haem groups for all derivatives. 3. In the alkaline pH range (about pH8.0) all the derivatives show the same charge as normal haemoglobin whereas in the acid pH range (about pH6.0) alpha(c) (2)beta(c) (2) differs by four protonic charges and alpha(c) (2)beta(2), alpha(2)beta(c) (2) by two protonic charges from normal haemoglobin, indicating that the expected number of ionizing groups have been removed. 4. alpha(c) (2)beta(2) and alpha(c) (2)beta(c) (2) show a 25% decrease in the alkaline Bohr effect, in contrast with alpha(2)beta(c) (2), which has the same Bohr effect as normal haemoglobin. 5. The deoxy form of alpha(c) (2)beta(c) (2) does not bind more CO(2) than the oxy form of alpha(c) (2)beta(c) (2), whereas alpha(c) (2)beta(2) and alpha(2)beta(c) (2) show intermediate binding. 6. The results reported confirm the hypothesis that, under physiological conditions, haemoglobin binds CO(2) through the four terminal alpha-amino groups and that the two terminal alpha-amino groups of alpha-chains are involved in the Bohr effect.
| S-EPMC1177110 | biostudies-other
Project description:Carbon monoxide (CO) is a known endogenous signaling molecule with potential therapeutic indications in treating inflammation, cancer, neuroprotection, and sickle cell disease among many others. One of the hurdles in using CO as a therapeutic agent is the development of pharmaceutically acceptable delivery forms for various indications. Along this line, we have developed organic CO prodrugs that allow for packing this gaseous molecule into a dosage form for the goal of "carbon monoxide in a pill." This should enable non-inhalation administration including oral and intravenous routes. These prodrugs have previously demonstrated efficacy in multiple animal models. To further understand the CO delivery efficiency of these prodrugs in relation to their efficacy, we undertook the first pharmacokinetic studies on these prodrugs. In doing so, we selected five representative prodrugs with different CO release kinetics and examined their pharmacokinetics after administration via oral, intraperitoneal, and intravenous routes. It was found that all three routes were able to elevate systemic CO level with delivery efficiency in the order of intravenous, oral, and intraperitoneal routes. CO prodrugs and their CO-released products were readily cleared from the circulation. CO prodrugs demonstrate promising pharmaceutical properties in terms of oral CO delivery and minimal drug accumulation in the body. This represents the very first study of the interplay among CO release kinetics, CO prodrug clearance, route of administration, and CO delivery efficiency.
| S-EPMC7606817 | biostudies-literature