Showing papers on "Myoglobin published in 2019"
TL;DR: SDS-PAGE analysis revealed that the ability of ROS-generating systems to facilitate protein oxidation was enhanced with MDA, which was responsible for the formation of protein cross-linking throughout incubation treatment.
117 citations
TL;DR: The pressure-induced color changes in meat are discussed in relation to modification of the myoglobin molecule, changes in the meat microstructure, and the impact of the presence of different chemical compounds and physical conditions during processing.
Abstract: High pressure (HP) treatment often results in discoloration of beef, lamb, pork, and poultry. The degree of color changes depends on the physical and chemical state of the meat, especially myoglobin, and the atmospheric conditions during and after pressurization. A decreased redness is attributed to a large degree to the oxidation of the bright red oxymyoglobin or the purplish deoxymyoglobin into the brownish metmyoglobin, as well as to the denaturation of myoglobin. Surely, the high myoglobin content makes beef more exposed to this discoloration compared to the white chicken meat. In addition, HP treatment causes denaturation of myofibrillar proteins followed by aggregation, consequently, changing the surface reflectance and increasing lightness. Other intrinsic and extrinsic factors may affect the pressure-induced color changes positively or negatively. In this review, the pressure-induced color changes in meat are discussed in relation to modification of the myoglobin molecule, changes in the meat microstructure, and the impact of the presence of different chemical compounds and physical conditions during processing.
61 citations
21 Apr 2019
TL;DR: Iron chelators treat iron overload, a condition often caused by transfusion therapies that are used to treat thalassemias and other anemias.
Abstract: Iron is an essential element of various metabolic processes in humans, including DNA synthesis, electron transport, and oxygen transport. Unlike other minerals, iron levels in the human body are controlled only by absorption. The mechanism of iron excretion is an unregulated process arrived at through loss in sweat, menstruation, shedding of hair and skin cells, and rapid turnover and excretion of enterocytes. In the human body, iron exists mainly in erythrocytes as the heme compound hemoglobin (approximately 2 g of iron in men and 1.5 g in women), to a lesser extent in storage compounds (ferritin and hemosiderin) and in muscle cells as myoglobin. Iron is also found bound to proteins (hemoprotein) and non-heme enzymes involved in oxidation-reduction reactions and the transfer of electrons (cytochromes and catalase).Additionally, approximately 2.2% of total body iron is found in the so-called labile pool, a poorly defined and reactive pool of iron that forms reactive oxygen species via the Fenton Reaction, which forms complexes with a drug class known as chelators. Iron chelators treat iron overload, a condition often caused by transfusion therapies used to treat thalassemias and other anemias.
42 citations
TL;DR: Mapping the photo-cleaved fragments onto crystallographic structures provides insight into the local structural changes that occur as protein unfolding progresses, which is coupled to global restructuring observed in the drift time profiles.
37 citations
TL;DR: The first evidence of formation pre-molten globule (PMG) in a protein in the presence of a crowding agent is reported, which is essential to unravel the mystery to solve the massively complicated problems involved in the proper folding of proteins in vivo.
34 citations
TL;DR: It is shown, that the IL anion affinity for water or the anion’s hydrogen-bond basicity controls the phase splitting behavior and thus [C4mim][N(CN)2] is able to greatly enhance two-phase region, enabling the most hydrophilic IL – [C3CO2] – to change the myoglobin partitioning behavior from salt-rich to the PEG-rich phase.
30 citations
TL;DR: This article investigated the interrelationships between different forms of myoglobin, lipid oxidation and protein carbonyls in minced pork packaged under modified atmosphere (30% CO2 and 70% O2) and stored at 4'°C for 12 days.
26 citations
TL;DR: Results elucidate a new function for myoglobin as a modulator of mitochondrial dynamics and reveal a novel pathway by which myoglobin decreases breast cancer cell proliferation and tumor growth by up-regulating mitofusin levels.
24 citations
TL;DR: These studies demonstrate that proximal ligand substitution provides a promising strategy to tune the reactivity of myoglobin-based carbene and nitrene transfer catalysts and provide a first, proof-of-principle demonstration of the viability of pyridine-, thiophene-, and aniline-based unnatural amino acids for metalloprotein engineering.
22 citations
22 citations
TL;DR: Myoglobin reconstituted with Ni tetradehydrocorrin was investigated as a model of F430-containing methyl-coenzyme M reductase which catalyzes anaerobic methane generation.
Abstract: Myoglobin reconstituted with Ni tetradehydrocorrin was investigated as a model of F430-containing methyl-coenzyme M reductase, which catalyzes anaerobic methane generation. The NiII tetradehydrocorrin complex has a NiII /NiI redox potential of -0.34 V vs. SHE and EPR spectroscopy indicates the formation of a NiI species upon reduction by dithionite. This redox potential is approximately 0.31 V more positive than that of F430. The NiI tetradehydrocorrin moiety is bound to the apo-form of myoglobin to yield the reconstituted protein. Methane gas is generated in the reaction of the model with methyl iodide in the presence of the reconstituted protein under reductive conditions, whereas the NiI complex itself does not produce methane gas. This is the first example of a protein-based functional model of F430-containing methyl-coenzyme M reductase.
TL;DR: In this paper, the interaction of quinoline yellow (QY) with myoglobin (Mb) at two different pH (3.5 and 7.4) was explored and binding results showed that interaction between QY and myoglobin is spontaneous and static in nature with high KSV value of 2.14
TL;DR: Results suggest that myoglobin deficiency activates compensatory mechanisms to sustain NO homeostasis and suggest that nitrate production in muscle originates from diet, the futile cycle of nitric oxide synthase 1 (NOS1) and/or oxidation of NO by oxymyoglobin.
TL;DR: This study suggests that muscle damage markers measured in blood and urine could serve as early diagnosis for pressure induced deep tissue injury.
Abstract: Pressure-induced deep tissue injury is a form of pressure ulcer which is difficult to detect and diagnose at an early stage, before the wound has severely progressed and becomes visible at the skin surface. At the present time, no such detection technique is available. To test the hypothesis that muscle damage biomarkers can be indicative of the development of deep tissue injury after sustained mechanical loading, an indentation test was performed for 2 h on the tibialis anterior muscle of rats. Myoglobin and troponin were analysed in blood plasma and urine over a period of 5 days. The damage as detected by the biomarkers was compared to damage as observed with T2 MRI to validate the response. We found that myoglobin and troponin levels in blood increased due to the damage. Myoglobin was also increased in urine. The amount of damage observed with MRI immediately after loading had a strong correlation with the maximal biomarker levels: troponin in blood rs = 0.94; myoglobin in blood rs = 0.75; and myoglobin in urine rs = 0.57. This study suggests that muscle damage markers measured in blood and urine could serve as early diagnosis for pressure induced deep tissue injury.
08 Jul 2019
TL;DR: The dissociation thermodynamics show that EBB- and TTAB-induced dissociation of heme is not significantly impacted by room temperature ionic liquids (RTILs), whereas SDS- induced dissociation is more dramatically impacted by all RTILs examined.
Abstract: The unique electrochemical properties of ionic liquids (ILs) have motivated their use as solvents for organic synthesis and green energy applications. More recently, their potential in pharmaceutical chemistry has prompted investigation into their effects on biomolecules. There is evidence that some ILs can destabilize proteins via a detergent-like manner; however, the mechanism still remains unknown. Our hypothesis is that if ILs are denaturing proteins via a detergent-like mechanism, detergent-mediated protein unfolding should be enhanced in the presence of ILs. The properties of myoglobin was examined in the presence of a zwitterionic (N,N-dimethyl-N-dodecylglycine betaine (Empigen BB®, EBB)), cationic (tetradecyltrimethylammonium bromide (TTAB)), and anionic (sodium dodecyl sulfate (SDS)) detergent as well as ILs based on alkylated imidazolium chlorides. Protein structure was measured through a combination of absorbance, fluorescence, and circular dichroism (CD) spectroscopy: absorbance and CD were used to monitor heme complexation to myoglobin, and tryptophan fluorescence quenching was used as an indicator for heme dissociation. Notably, the detergents tested did not fully denature the protein but instead resulted in loss of the heme group. At low IL concentrations, heme dissociation remained a traditional, cooperative process; at high concentrations, ILs with increased detergent-like character exhibited a more complex pattern, which is most likely attributable to micellization of the ionic liquids or direct denaturation or heme dissociation induced by the ILs. These trends were consistent across all species of detergents. 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence was further used to characterize micelle formation in aqueous solutions containing detergent and ionic liquid. The dissociation thermodynamics show that EBB- and TTAB-induced dissociation of heme is not significantly impacted by room temperature ionic liquids (RTILs), whereas SDS-induced dissociation is more dramatically impacted by all RTILs examined. Together, these results indicate a complex interaction of detergents, likely based on headgroup charge, and the active component of RTILs to influence heme dissociation and potentially protein denaturation.
TL;DR: The difference in magnitude of O2heme and Heme pulses with each heartbeat might suggest different anatomical locations of these signals, for which calibrating with just one of the signals instead of the ratio of both is proposed.
Abstract: Near-infrared spectroscopy (NIRS) uses the relative absorption of light at 850 and 760 nm to determine skeletal muscle oxygen saturation. Previous studies have used the ratio of both signals to report muscle oxygen saturation. Purpose: The purpose of this pilot study is to assess the different approaches used to represent muscle oxygen saturation and to evaluate the pulsations of oxygenated hemoglobin/myoglobin (O2heme) and deoxygenated hemoglobin/myoglobin (Heme) signals. Method: Twelve participants, aged 20–29 years, were tested on the forearm flexor muscles using continuous-wave NIRS at rest. Measurements were taken during 2–3 min rest, physiological calibration (5 min ischemia), and reperfusion. Ten participants were included in the study analysis. Results: There was a significant difference in pulse size between O2heme and Heme signals at the three locations (p < 0.05). Resting oxygen saturation was 58.8% + 9.2%, 69.6% + 3.9%, and 89.2% + 6.9% when calibrated using O2heme, the tissue oxygenation/saturation index (TSI), and Heme, respectively. Conclusion: The difference in magnitude of O2heme and Heme pulses with each heartbeat might suggest different anatomical locations of these signals, for which calibrating with just one of the signals instead of the ratio of both is proposed. Calculations of physiological calibration must account for increased blood volume in the tissue because of the changes in blood volume, which appear to be primarily from the O2heme signal. Resting oxygen levels calibrated with Heme agree with theoretical oxygen saturation.
TL;DR: In this article, the effect of NaNO2 in hydroxyl radical-mediated oxidative damage of yak meat myoglobin was investigated using laser micro-Raman spectroscopy and Fourier transform infrared spectrograms.
Abstract: The effect of NaNO2 in hydroxyl radical-mediated oxidative damage of yak meat myoglobin was investigated. Laser micro-Raman spectroscopy and Fourier Transform Infrared spectroscopy were used to assess protein (carbonyls, total sulfhydryl and Disulfide bonds) oxidation, atomic (or molecular) interactions and secondary structural changes. The addition of NaNO2 during the oxidation of myoglobin significantly reduced the content of carbonyl and disulfide bonds and protected the sulfhydryl groups from hydroxyl radical oxidation (P 0.05). At the same time, NaNO2 had an inhibitory effect on the expansion of the hemoglobin center size and the transition of Fe from a low spin state to a high spin state caused by radical-oxidized. These findings suggest that NaNO2 has potential for treatment effects in a hydroxyl radical-oxidized myoglobin.
Bellvitge University Hospital1, Karolinska University Hospital2, Science for Life Laboratory3, Harry Perkins Institute of Medical Research4, Spanish National Research Council5, University of Modena and Reggio Emilia6, University of Western Australia7, University of Natural Resources and Life Sciences, Vienna8, Victor Chang Cardiac Research Institute9, Autonomous University of Barcelona10, Karolinska Institutet11, University of Paris12, Claude Bernard University Lyon 113, Katholieke Universiteit Leuven14, Leiden University Medical Center15, Radboud University Nijmegen16, University of Antwerp17, University of Tampere18, University of Helsinki19, University of Barcelona20
TL;DR: A genetic variant in the MB gene is reported that associates with myoglobinopathy, an autosomal dominant progressive myopathy, and altered oxygen binding properties of the mutant protein, which preliminary studies show may result in elevated superoxide levels at the cellular level.
Abstract: Myoglobin, encoded by MB, is a small cytoplasmic globular hemoprotein highly expressed in cardiac myocytes and oxidative skeletal myofibers. Myoglobin binds O2, facilitates its intracellular transport and serves as a controller of nitric oxide and reactive oxygen species. Here, we identify a recurrent c.292C>T (p.His98Tyr) substitution in MB in fourteen members of six European families suffering from an autosomal dominant progressive myopathy with highly characteristic sarcoplasmic inclusions in skeletal and cardiac muscle. Myoglobinopathy manifests in adulthood with proximal and axial weakness that progresses to involve distal muscles and causes respiratory and cardiac failure. Biochemical characterization reveals that the mutant myoglobin has altered O2 binding, exhibits a faster heme dissociation rate and has a lower reduction potential compared to wild-type myoglobin. Preliminary studies show that mutant myoglobin may result in elevated superoxide levels at the cellular level. These data define a recognizable muscle disease associated with MB mutation.
TL;DR: In this article, photodissociation spectra near the Soret region were acquired for hydrated myoglobin (Mb) ions isolated in the gas phase, which had a large red shift relative to that from an acidic aqueous s...
Abstract: Photodissociation spectra near the Soret region were acquired for hydrated myoglobin (Mb) ions isolated in the gas phase. The spectra had a large red shift relative to that from an acidic aqueous s...
TL;DR: A fluorometric assay for cardiac myoglobin (Mb), a marker for myocardial infarction, is described based on pyrene-modified anti-Mb aptamer and GO (graphene oxide) through fluorescence quenching and subsequent recovery.
Abstract: The authors describe a fluorometric assay for cardiac myoglobin (Mb), a marker for myocardial infarction. An Mb-binding aptamer was labeled with pyrene and adsorbed on the surface of graphene oxide (GO) via noncovalent and reversible binding forces. This causes the fluorescence of pyrene (best measured at excitation/emission wavelengths of 275/376 nm) to be quenched. However, fluorescence is restored on addition of pyrene due to the strong affinity between Mb and aptamer which causes its separation from GO. Fluorescence increases linearly in the 5.6–450 pM Mb concentration range, and the lower detection limit is 3.9 pM (S/N = 3). The assay was applied to the determination of cardiac Mb in spiked serum, and satisfactory results were obtained.
TL;DR: An effective theory approach to investigate the phase properties of globular proteins is developed and suggests that the ligand entry and exit is driven by large scale collective motions that destabilize the myoglobin F-helix.
Abstract: We develop an effective theory approach to investigate the phase properties of globular proteins. Instead of interactions between individual atoms or localized interaction centers, the approach builds directly on the tertiary structure of a protein. As an example we construct the phase diagram of (apo)myoglobin with temperature (T) and acidity (pH) as the thermodynamical variables. We describe how myoglobin unfolds from the native folded state to a random coil when temperature and acidity increase. We confirm the presence of two molten globule folding intermediates, and we predict an abrupt transition between the two when acidity changes. When temperature further increases we find that the abrupt transition line between the two molten globule states terminates at a tricritical point, where the helical structures fade away. Our results also suggest that the ligand entry and exit is driven by large scale collective motions that destabilize the myoglobin F-helix.
TL;DR: In this paper, the myoglobin-SDDS interaction at different pH, ranging from 5 to 8 has been studied and it shows that pH has very little effect on the conformational change of myoglobin and SDDS system.
TL;DR: This study establishes a novel mechanism for covalent modification of proteins by 2-alkenals, in which heme iron is involved in the formation of the alkanoic acid-histidine adducts.
Abstract: α,β-Unsaturated aldehydes generated during lipid peroxidation, such as 2-alkenals, give rise to protein degeneration in a variety of pathological states. 2-Alkenals are highly reactive toward nucleophilic amino acid residues, such as histidine and lysine, to form Schiff base adducts or Michael addition adducts. In this study, upon the reaction of hemoglobin with 2-octenal, we unexpectedly detected a product corresponding to the reduced form of the 2-octenal-histidine Michael adduct plus 14 mass unit. Based on the LC-ESI-MS/MS analysis of synthetic adduct candidates, the adduct was identified to be Nτ-(1-carboxyheptan-2-yl)-histidine (CHH), a novel alkanoic acid-type histidine adduct. The alkanoic acid-histidine adducts were detected in the 2-alkenal-treated hemoglobin and myoglobin, but not in the 2-alkenal-treated cytochrome c and transferrin. The addition of hemin to the reaction mixture, containing a non-heme protein and 2-alkenals, resulted in the formation of the alkanoic acid-histidine adducts, suggesting that a heme iron may play a role in the oxidation of covalently modified proteins. Moreover, using the stable isotope dilution method, we showed evidence for the endogenous formation of CHH in red blood cells exposed to hydrogen peroxide. Thus, this study establishes a novel mechanism for covalent modification of proteins by 2-alkenals, in which heme iron is involved in the formation of the alkanoic acid-histidine adducts. The potential implications of this novel adduct are discussed.
TL;DR: This paper describes how PyMOL is integrated into a module on the myoglobin/hemoglobin system to elaborate the relationship between protein structure and function.
Abstract: A goal for biochemistry instructors is to support their students’ ability to critically analyze protein structure and its relationship to function. To do this, biochemistry instructors strategicall...
TL;DR: The X-ray crystal structure of F43Y/T67R myoglobin revealed unique Tyr-heme double cross-links between Tyr43 and the heme 4-vinyl group, which represents a novel post-translational modification of heme proteins.
05 Mar 2019
TL;DR: The concept that high-sensitivity cardiac troponin immunoassays outperform creatine kinase MB (CK-MB) and myoglobin in the diagnostics of acute coronary syndrome has been put forward more than 10 years ago, and is now virtually incontestable.
Abstract: The concept that high-sensitivity cardiac troponin immunoassays outperform creatine kinase MB (CK-MB) and myoglobin in the diagnostics of acute coronary syndrome has been put forward more than 10 years ago, and is now virtually incontestable. In the seminal study of Keller et al . (1), cardiac troponins, myoglobin and CK-MB were measured in over 1,800 consecutive patients admitted with suspected acute myocardial infarction. In all patients, the diagnostic performance (area under the curve, AUC) of both high-sensitivity cardiac troponin I (cTnI) (AUC, 0.96) and high-sensitivity cardiac troponin T (AUC, 0.85) was found to higher than that of both myoglobin (AUC, 0.82) and CK-MB (AUC, 0.73). Even more importantly, the early (i.e., <3 hours after onset of chest pain) negative and positive predictive values were also higher for high-sensitivity cTnI (0.94 and 0.82, respectively) than for myoglobin (0.87 and 0.64, respectively).
TL;DR: The data illustrate that the group 1 truncated Hb fold can tolerate diverse rearrangement of the heme environment and has a strong tendency to use two protein side chains as iron ligands despite accompanying structural perturbations.
TL;DR: Data indicate oxidizing HOCl promotes Mb oxidation but not chlorination and that oxidized Mb shows altered Mb peroxidase-like activity and diminished rates of one-electron reduction by cytochrome b5 reductase, possibly affecting oxygen storage and transport however, Mb-catalase- like antioxidant activity remains unchanged.
Abstract: Activated neutrophils release myeloperoxidase that produces the potent oxidant hypochlorous acid (HOCl). Exposure of the oxygen transport protein horse heart myoglobin (hhMb) to HOCl inhibits Iron III (Fe(III))-heme reduction by cytochrome b5 to oxygen-binding Iron II (Fe(II))Mb. Pathological concentrations of HOCl yielded myoglobin oxidation products of increased electrophoretic mobility and markedly different UV/Vis absorbance. Mass analysis indicated HOCl caused successive mass increases of 16 a.m.u., consistent serial addition of molecular oxygen to the protein. By contrast, parallel analysis of protein chlorination by quantitative mass spectrometry revealed a comparatively minor increase in the 3-chlorotyrosine/tyrosine ratio. Pre-treatment of hhMb with HOCl affected the peroxidase reaction between the hemoprotein and H2O2 as judged by a HOCl dose-dependent decrease in spin-trapped tyrosyl radical detected by electron paramagnetic resonance (EPR) spectroscopy and the rate constant of 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) oxidation. By contrast, Mb catalase-like antioxidant activity remained unchanged under the same conditions. Notably, HOCl-modification of Mb decreased the rate of ferric-to-ferrous Mb reduction by a cytochrome b5 reductase system. Taken together, these data indicate oxidizing HOCl promotes Mb oxidation but not chlorination and that oxidized Mb shows altered Mb peroxidase-like activity and diminished rates of one-electron reduction by cytochrome b5 reductase, possibly affecting oxygen storage and transport however, Mb-catalase-like antioxidant activity remains unchanged.