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PubMed2004

Preparation of artificial 2-, 3-, 4- and 8-domain myoglobins and comparison of their autoxidation rates.

Although most hemoglobins and myoglobins consist of 15-kDa single-domain subunits, structurally unusual hemoglobins, such as Artemia 9-domain and Barbatia 2-domain hemoglobins, occur naturally in several invertebrates. These hemoglobins appear to be the result of gene duplication and fusion. Using cDNA coding for the open reading frame of Aplysia kurodai myoglobin, artificial cDNA inserts corresponding to contiguous dimer, trimer, tetramer and octamer myoglobins (2-, 3-, 4- and 8-domain myoglobins) were prepared and cloned into pMAL or pQE plasmids. These artificial myoglobins and wild-type single-domain myoglobins were successfully expressed in Escherichia coli in the heme-attached, oxygenated form. Myoglobin was purified partially by ammonium sulfate fractionation and gel filtration, and autoxidation rates were examined. The autoxidation rates of recombinant wild-type myoglobins with MBP or hexameric His tag were comparable to those of native myoglobin, suggesting that the recombinant proteins appear to be properly folded and that the N-terminal MBP or His tag does not have an affect on the rate. On the other hand, the rates were significantly decreased in the 2- and 3-domain myoglobins (50% and 30% of the single-domain myoglobins, respectively). The rates for 4- and 8-domain myoglobins were similar to those for 3-domain myoglobin. These results indicate that the artificial poly-domain structure of myoglobin is more stable than the usual single-domain myoglobin from the viewpoint of storage of bound dioxygen.

Base Sequence↗
PubMed1982

A possible immunodominant epitope recognized by murine T lymphocytes immune to different myoglobins.

We find that a single region on the surface of different species of myoglobin appears to be immunodominant for T lymphocytes, even though the residues in that region vary sufficiently that the T cells immune to one myoglobin do not crossreact with other myoglobins bearing substitutions at that site. Immunization of B10.S mice with sperm whale myoglobin elicits T-lymphocyte populations capable of recognizing sperm whale myoglobin but not horse myoglobin, whereas the converse is true when these mice are immunized with horse myoglobin. Using a series of myoglobin variants, we tested the effect of changes in primary sequence on the T-lymphocyte proliferative response. We were able to divide the myoglobin variants into two groups, depending on whether they cross stimulate sperm whale immune or horse immune T lymphocytes. The patterns of cross stimulation of both populations of myoglobin immune T lymphocytes were explained by amino acid substitutions at position 109. However, because sperm whale and horse myoglobin differ at this residue (glutamate vs. aspartate, respectively), T lymphocytes immune to each myoglobin do not crossreact with the other myoglobin. Additional data suggest that this immunodominant epitope also includes other residues nearby on the surface of the native molecule. Mixing experiments showed that the specificity was that of T lymphocytes and not antigen-presenting cells. Monoclonal anti-I-A blocking studies showed that both myoglobins are presented in association with the same Ia antigen. Possible explanations for the apparent immunodominance of this antigenic epitope, consisting of residue 109 and nearby residues on the surface of both myoglobins, include a peculiar immunogenicity of the surface topography of this site of a preferred orientation of the molecule imposed by antigen-presenting cells when T cells first encounter the antigen. The latter explanation is related to but distinct from "determinant selection." T-cell recognition of conformation is discussed.

Amino Acid Sequence↗
PubMed2005

Prognostic value, kinetics and effect of CVVHDF on serum of the myoglobin and creatine kinase in critically ill patients with rhabdomyolysis.

BACKGROUND: (I) To investigate the kinetics of the myoglobin and creatine kinase (CK) in rhabdomyolysis. Especially to describe those patients in whom an isolated increase in the myoglobin or the CK occurred at a later stage. (II) To evaluate the sensitivity of the myoglobin and the CK as prognostic tools for the development of Acute renal failure (ARF). (III) To investigate the effect of continuous venovenous haemodiafiltration (CVVHDF) on the myoglobin elimination in ARF. PATIENTS AND METHODS: Prospective and retrospective cohort study carried out in an ICU of a university hospital. A total of 47 critically ill patients with rhabdomyolysis and a plasma myoglobin > 5000 microg l(-1) were admitted between July 1998 and July 2003. RESULTS: (I) The myoglobin peaked 0.66 +/- 0.6 days before the CK. The elimination kinetics of the myoglobin was faster than for the CK. (II) Fifty percent developed ARF. Mortality in the ARF patients was 52% compared to 14% in the non-ARF patients. The sensitivity and specificity of developing ARF were higher with the myoglobin in comparison to the CK. (III) In non-ARF, t(1/2) CK was 25.5 h and t(1/2) myoglobin was 17 h (13-23). In those with ARF treated with CVVHDF, t(1/2) CK was 24.8 and t(1/2) myoglobin was 21 h (17-29). CONCLUSION: (I) The myoglobin peaked earlier than the CK. (II) The myoglobin was a better prognostic tool than the CK. However, the myoglobin also has a wide interindividual range. (III) Though the myoglobin is eliminated in ultrafiltration t(1/2) myoglobin, it was not faster in patients with ARF treated with CVVHDF compared to non-ARF patients.

Acute Kidney Injury↗
PubMed1991

[Evaluation of serum myoglobin level in patients with muscular disorder and renal failure].

Since myoglobin is a low molecular weight proteins and most serum myoglobin is usually excreted into the urine, but serum myoglobin is elevated in patients with renal failure. This elevation hampers diagnosis of muscular damage in patients with renal failure. We studied the influence of renal function on serum myoglobin level and estimated corrected myoglobin levels. We first examined the correlation of serum myoglobin level with levels of serum creatinine and serum beta 2 microglobulin in patients without muscular damage. Creatinine level was more highly correlated with serum myoglobin level than with beta 2 microglobulin level. Measured myoglobin level was corrected using the regression line obtained from the correlation between levels of myoglobin and creatinine, and the corrected myoglobin levels thus obtained were within a reasonable range. The influence of renal failure was compensated for by this correction. We then measured myoglobin level and creatine kinase activity in patients with various heart muscle or skeletal muscle diseases, with or without renal failure, and compared measured myoglobin levels with the corrected ones. In these patients, myoglobin level changed faster than such muscle enzymes as creatine kinase. Thereafter, we found that the stage and degree of muscular damage could be estimated from both corrected myoglobin level and creatine kinase activity, even in patients with renal failure. In conclusion, corrected serum myoglobin level might be a useful diagnostic marker of muscle damage even in patients with renal failure.

Creatine Kinase↗
PubMed1990

[Myoglobin release and renal function in polytraumatized patients in intensive care].

The excessive release of myoglobin following extensive skeletal muscle trauma, burns, and myopathies may result in renal dysfunction. Due to its molecular size, myoglobin is filtered through the glomerulus and is in part reabsorbed by the tubular system. intraluminal deposition of myoglobin following renal hypoperfusion and the impact of endogenous mediators on cell function contribute to the pathogenesis of acute renal failure. The present study was aimed to investigate the relation between myoglobin and renal function in polytraumatized patients. Thirty-four patients with an Injury Severity Score (ISS) of 28 +/- 3.1 (SEM) and a mean age of 39.5 years (range 18-70) were studied prospectively. Myoglobin, sodium, and creatinine concentrations in plasma and urine were determined 8-hourly. Myoglobin excretion, fractional myoglobin excretion, myoglobin clearance, creatinine clearance, and fractional excretion of sodium were calculated. The mean concentration of plasma myoglobin on the 1st day post-trauma was 3087 ng/ml. A continuous decrease in plasma myoglobin concentration could be observed, with a mean value of 497 ng/ml on day 7. The myoglobin concentration in urine showed marked fluctuations: the mean values were 3.37-4.12 mg/ml on day 1 and 0.78-1.34 mg/ml on day 7. There was no correlation between plasma and urine myoglobin concentrations. The myoglobin concentration increased during the period of observation, but there was no correlation with the creatinine clearance. The fractional excretion of myoglobin was in the range of 1% to 14%. There was no correlation between the fractional excretions of myoglobin and sodium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Amino acid sequence of myoglobin from the chiton Liolophura japonica and a phylogenetic tree for molluscan globins.

Myoglobin was isolated from the radular muscle of the chiton Liolophura japonica, a primitive archigastropodic mollusc. Liolophura contains three monomeric myoglobins (I, II, and III), and the complete amino acid sequence of myoglobin I has been determined. It is composed of 145 amino acid residues, and the molecular mass was calculated to be 16,070 D. The E7 distal histidine, which is replaced by valine or glutamine in several molluscan globins, is conserved in Liolophura myoglobin. The autoxidation rate at physiological conditions indicated that Liolophura oxymyoglobin is fairly stable when compared with other molluscan myoglobins. The amino acid sequence of Liolophura myoglobin shows low homology (11-21%) with molluscan dimeric myoglobins and hemoglobins, but shows higher homology (26-29%) with monomeric myoglobins from the gastropodic molluscs Aplysia, Dolabella, and Bursatella. A phylogenetic tree was constructed from 19 molluscan globin sequences. The tree separated them into two distinct clusters, a cluster for muscle myoglobins and a cluster for erythrocyte or gill hemoglobins. The myoglobin cluster is divided further into two subclusters, corresponding to monomeric and dimeric myoglobins, respectively. Liolophura myoglobin was placed on the branch of monomeric myoglobin lineage, showing that it diverged earlier from other monomeric myoglobins. The hemoglobin cluster is also divided into two subclusters. One cluster contains homodimeric, heterodimeric, tetrameric, and didomain chains of erythrocyte hemoglobins of the blood clams Anadara, Scapharca, and Barbatia. Of special interest is the other subcluster. It consists of three hemoglobin chains derived from the bacterial symbiontharboring clams Calyptogena and Lucina, in which hemoglobins are supposed to play an important role in maintaining the symbiosis with sulfide bacteria.

Amino Acid Sequence↗
PubMed1960

The binding of myoglobin by plasma protein.

When added to dog plasma in vitro and in vivo, myoglobin was bound to plasma protein in a concentration which, maximally, averaged 21 +/- 6 mg. per cent. Electrophoretically, bound myoglobin was separated from free myoglobin and migrated between alpha-2 and beta globulin. The electrophoretic characteristics of protein-bound myoglobin were similar to, although not identical with, those of protein-bound hemoglobin. The maximal binding capacity of plasma for myoglobin was less than for hemoglobin, which averaged 123 mg. per cent. At concentrations below the maximal binding capacity, from 15 to 50 per cent of the myoglobin was in the free, unbound state, differing from hemoglobin which was completely bound at all concentrations below the binding capacity. When myoglobin and hemoglobin were added together to plasma, hemoglobin appeared to interfere with the binding of myoglobin or to replace it at the binding sites. Myoglobin, however, did not appear to interfere with the binding of hemoglobin. These observations suggested that myoglobin and hemoglobin were bound at least in part by the same protein. When myoglobin was given intravenously, free myoglobin was excreted in the urine, whereas protein-bound myoglobin was not excreted. This suggests that protein-binding contributes to or determines the apparent renal threshold to myoglobin.

Animals↗
PubMed1992

Acute myocardial infarction size and myoglobin release into serum.

The kinetics of myoglobin release after acute myocardial infarction were studied. Various algorithms for calculation of infarct size, based on immunonephelometric determination of myoglobin and cumulative myoglobin release into the circulation were compared. The cumulative myoglobin release and maximal serum myoglobin concentration were compared with various measures of infarct size: cumulative release of creatine kinase, electrocardiographic changes, and left ventricular ejection fraction. After acute myocardial infarction, time to peak for myoglobin in serum was correlated with time to peak for creatine kinase (r = 0.645). On average, the myoglobin concentration peaked 8.8 h earlier than creatine kinase activity. The rate of elimination of myoglobin showed a large variation (0.041-0.628 h-1) and was not correlated with the elimination rate of creatine kinase. The elimination rate of myoglobin after acute myocardial infarction was shown to depend on the patient's age and infarct size. The elimination constant of myoglobin is preferably estimated on an individual basis in large and complicated infarctions. Cumulative myoglobin release correlated with algorithms based on the cumulative release of creatine kinase (r = 0.622) and its isoenzyme MB (r = 0.660), and to a lesser extent with the residual left ventricular ejection fraction (r = 0.513) and the sum of ST-segment deviations on electrocardiography (r = 0.469). Maximal myoglobin values in serum correlated moderately with the calculated infarct size (r = 0.488; based on creatine kinase-MB) and electrocardiographic changes (r = 0.554). In combination with fast immunological methods for myoglobin determination, myoglobin peak height offers the advantage of providing reliable results within 12 h after onset of symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1999

Myoglobin clearance and removal during continuous venovenous hemofiltration.

Myoglobin has a relatively high molecular weight of 17,000 Da and is poorly cleared by dialysis (diffusion). However, elimination of myoglobin might be enhanced by an epuration modality based on convection for solute clearances. We present a single case of myoglobin-induced renal failure (peak creatine kinase level: 313,500 IU/l) treated by continuous venovenous hemofiltration (CVVH). Our purpose was to evaluate the efficiency of such a modality using an ultrafiltration rate of 2 to 3 l/h for myoglobin removal and clearance. The hemofilter was a 0.9 m(2) polyacrylonitrile (AN69) membrane Multiflow-100 (Hospal-Gambro, St-Leonard, Canada) and the blood flow rate was maintained at 150 ml/min by an AK-10 pump (Hospal-Gambro, St-Leonard, Canada). The ultrafiltration bag was placed 60 cm below the hemofilter and was free of pump control or suction device. Serum myoglobin concentration was 92,000 microg/l at CVVH initiation and dropped to 28,600 microg/l after 18 h of the continuous modality. The mean sieving coefficient for myoglobin was 0.6 during the first 9 h of therapy and this decreased to 0.4 during the following 7 h. Mean clearance of myoglobin was 22 ml/min, decreasing to 14 ml/min during corresponding periods, while the mean ultrafiltration rates were relatively stable at 2,153 +/- 148 ml/h and 2,074 +/- 85 ml/h, respectively. In contrast to myoglobin, the sieving coefficeint for urea, creatinine, and phosphorus remained stable at 1.0 during the first 16 h of CVVH. More than 700 mg of myoglobin were removed by CVVH during the entire treatment. In conclusion, considerable amounts of myoglobin can be removed by an extracorporeal modality allowing important convective fluxes and middle molecule clearances, such as CVVH at a rate of 2 to 3 l/h using an AN69 hemofilter. If myoglobin clearance had been maintained at 22 ml/min, 32 l of serum would have been cleared per day. However, the sieving coefficient of myoglobin decreased over time, probably as a consequence of protein coating and/or blood clotting of the hemofilter. Whereas myoglobin can be removed by CVVH, it remains unknown at this point if such a modality, applied early, can alter or shorten the course of myoglobinuric acute renal failure.

Acrylic Resins↗
PubMed2004

A change in serum myoglobin to detect acute myocardial infarction in patients with normal troponin I levels.

We sought to determine the sensitivity of a change in myoglobin for acute myocardial infarction (AMI) in patients who had normal levels of troponin I at presentation. Myoglobin increases as soon as 1 to 2 hours after symptom onset in AMI. The change in myoglobin may help identify AMI in patients with normal cardiac levels of troponin I on admission. A total of 817 consecutive patients who were examined in the emergency department for possible AMI were studied. In patients whose electrocardiograms were nondiagnostic, we measured levels of myoglobin and cardiac troponin I at presentation, at 90 minutes, and at 3 and 9 hours. Patients whose initial levels of myoglobin (<200 ng/ml) and cardiac troponin I (<0.4 ng/ml) were normal underwent receiver-operating characteristic curve analysis to determine the best cutpoint for a myoglobin increase from 0 to 90 minutes. Overall, 75 patients (9%) were diagnosed with AMI, including 27 patients with normal cardiac levels of troponin I at presentation. An increase of 20 ng/ml of myoglobin from 0 to 90 minutes provided maximal diagnostic utility in patients who did not have increased levels of myoglobin or cardiac troponin I at presentation. In the absence of an increased level of cardiac troponin I or myoglobin at presentation in the emergency department, a change >or=20 ng/ml of myoglobin at 90 minutes produced 83.3% sensitivity, 88.6% specificity, and 99.5% negative predictive value for AMI. The combined sensitivity of levels of cardiac troponin I and myoglobin and a change >or=20 ng/ml of myoglobin over 90 minutes was 97.3%. In emergency department patients with normal cardiac levels of troponin I at presentation, a change in myoglobin provides a highly accurate diagnosis of AMI within 90 minutes.

Aged↗
PubMed2004

Analysis of myoglobin adsorption to Cu(II)-IDA and Ni(II)-IDA functionalized Langmuir monolayers by grazing incidence neutron and X-ray techniques.

The adsorption of myoglobin to Langmuir monolayers of a metal-chelating lipid in crystalline phase was studied using neutron and X-ray reflectivity (NR and XR) and grazing incidence X-ray diffraction (GIXD). In this system, adsorption is due to the interaction between chelated divalent copper or nickel ions and the histidine moieties at the outer surface of the protein. The binding interaction of histidine with the Ni-IDA complex is known to be much weaker than that with Cu-IDA. Adsorption was examined under conditions of constant surface area with an initial pressure of 40 mN/m. After approximately 12 h little further change in reflectivity was detected, although the surface pressure continued to slowly increase. For chelated Cu2+ ions, the adsorbed layer structure in the final state was examined for bulk myoglobin concentrations of 0.10 and 10 microM. For the case of 10 microM, the final layer thickness was approximately 43 A. This corresponds well to the two thicker dimensions of myoglobin in the native state (44 A x 44 A x 25 A) and so is consistent with an end-on orientation for this disk-shaped protein at high packing density. However, the final average volume fraction of amino acid segments in the layer was 0.55, which is substantially greater than the value of 0.44 calculated for a completed monolayer from the crystal structure. This suggests an alternative interpretation based on denaturation. GIXD was used to follow the effect of protein binding on the crystalline packing of the lipids and to check for crystallinity within the layer of adsorbed myoglobin. Despite the strong adsorption of myoglobin, very little change was observed in the structure of the DSIDA film. There was no direct evidence in the XR or GIXD for peptide insertion into the lipid tail region. Also, no evidence for in-plane crystallinity within the adsorbed layer of myoglobin was observed. For 0.1 microM bulk myoglobin concentration, the average segment volume fraction was only 0.13 and the layer thickness was < or = 25 A. Adsorption of myoglobin to DSIDA-loaded with Ni2+ was examined at bulk concentrations of 10 and 50 microM. At 10 microM myoglobin, the adsorbed amount was comparable to that obtained for adsorption to Cu2+-loaded DSIDA monolayers at 0.1 M. But interestingly, the adsorbed layer thickness was 38 A, substantially greater than that obtained at low coverage with Cu-IDA. This indicates that either there are different preferred orientations for isolated myoglobin molecules adsorbed to Cu-IDA and Ni-IDA monolayer films or else myoglobin denatures to a different extent in the two cases. Either interpretation can be explained by the very different binding energies for individual interactions in the two cases. At 50 microM myoglobin, the thickness and segement volume fraction in the adsorbed layer for Ni-IDA were comparable to the values obtained with Cu-IDA at 10 microM myoglobin.

Adsorption↗
PubMed1998

Amino acid sequence, spectral, oxygen-binding, and autoxidation properties of indoleamine dioxygenase-like myoglobin from the gastropod mollusc Turbo cornutus.

Myoglobin was isolated from the radular muscle of the archaeogastropod mollusc Turbo cornutus (Turbinidae). This myoglobin is a monomer carrying one protoheme group; the molecular mass was estimated by SDS-PAGE to be about 40 kDa, 2.5 times larger than that of usual myoglobin. The cDNA-derived amino acid sequence of 375 residues was determined, of which 327 residues were identified directly by chemical sequencing of internal peptides. The amino acid sequence of Turbo myoglobin showed no significant homology with any other usual 16-kDa globins, but showed 36% identity with the myoglobin from Sulculus diversicolor (Haliotiidae) and 27% identity with human indoleamine 2,3-dioxygenase, a tryptophan-degrading enzyme containing heme. Thus, the Turbo myoglobin can be counted among the myoglobins which evolved from the same ancestor as that of indoleamine 2,3-dioxygenase. The absorbance ratio of gamma to CT maximum (gamma/CT) of Turbo metmyoglobin was 17.8, indicating that this myoglobin probably possesses a histidine residue near the sixth coordination position of heme iron. The Turbo myoglobin binds oxygen reversibly. Its oxygen equilibrium properties are similar to those of Sulculus myoglobin, giving P50 = 3.5 mm Hg at pH 7.4 and 20 degrees C. The pH dependence of autoxidation of Turbo oxymyoglobin was quite different from that of mammalian myoglobin, suggesting a unique protein folding around the heme cavity of Turbo myoglobin. A kinetic analysis of autoxidation indicates that the amino acid residue with pKa = 5.4 is involved in the reaction. The autoxidation reaction was enhanced markedly at pH 7.6, but not at pH 5.5 and 6.3 in the presence of tryptophan. We suggest that a noncatalytic binding site for tryptophan, in which several dissociation groups with pKa > or = 7.6 are involved, remains in Turbo myoglobin as a relic of molecular evolution.

Amino Acid Sequence↗
PubMed1989

Myoglobin in third trimester amniotic fluid of human pregnancy--a potential indicator of fetal hypoxia.

195 amniotic fluid samples from the third trimester were examined for their content of myoglobin by means of radio-immunoassay. 151 of the samples were obtained intrapartum, the rest (44) was taken antepartum by transabdominal amniocentesis within one week prior to delivery. Depending on the myoglobin levels measured, different amniotic fluid groups were defined: (A) amniotic fluids containing no myoglobin or traces of it (less than 3 ng/ml), (B) amniotic fluids with moderately elevated myoglobin levels (3-10 ng/ml), (C) amniotic fluids with high myoglobin levels (greater than 10 ng/ml). Myoglobin levels above 3 ng/ml could be measured in 98 of the 151 samples taken intrapartum. In the amniotic fluids drawn antepartum the proportion of "myoglobin-positive" samples (greater than 3 ng/ml) amounted to only 22.7% (10 out of 44 samples). In pregnancies with amniotic fluids showing high myoglobin levels intrapartum, the prevalence of meconium staining of the samples, pathological cardiotocograms intrapartum and metabolic acidoses in umbilical artery blood samples was significantly higher than in pregnancies with myoglobin-negative amniotic fluids. The frequency of cesarean sections for fetal distress rose with increasing myoglobin levels in amniotic fluid, being 5.7, 13, and 18.2% in Group A, B and C respectively. In the pregnancies in which the amniotic fluid samples were taken antepartum, the prevalence of meconium-stained amniotic fluid increased with elevating amniotic fluid myoglobin (p less than 0.05, Group A vs. Group C). The frequency of cesarean sections for fetal distress and of neonatal depression immediately after delivery was considerably heightened in the cases with myoglobin-positive amniotic fluids antepartum compared to those with myoglobin-negative liquor.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniocentesis↗
PubMed1997

Conservation of the myoglobin gene among Antarctic notothenioid fishes.

We determined the myoglobin cDNA sequence for seven Antarctic notothenioid fish species. These data identify mutations in the myoglobin gene for Champsocephalus gunnari and Pagetopsis macropterus, two icefish species that lack detectable quantities of the polypeptide but express myoglobin mRNA. a third species lacking myoglobin polypeptide, Chaenocephalus aceratus, is devoid of myoglobin mRNA and accordingly failed to produce myoglobin products on polymerase chain reaction (PCR) amplification. Myoglobin cDNA sequences were highly conserved among the species the express the protein, particularly in the coding region. Sequence variation among the myoglobin-expressing channichthyid species was 2.0% to 2.9% in the coding region and 2.6% to 3.3% over the entire cDNA. The same extent of variation, 1.6% to 3.2% in the coding sequence and 2.8% to 3.7% overall, was observed between the icefishes and more distantly related, red-blooded nototheniid species. The two species expressing mutant myoglobin mRNA, C. gunnari and P. macropterus, exhibited the highest degree of sequence variation among the fish myoglobins examined. Drift in the myoglobin sequence in these two species, and conservation of myoglobin cDNA among fishes from two distinct families, suggest that a selective pressure operates to maintain myoglobin in the species that express the protein.

Amino Acid Sequence↗
PubMed2003

Evidence of met-form myoglobin from Theliostyla albicilla radular muscle.

Gastropod mollusc myoglobins provide interesting clues to the evolution of this family of proteins. In addition to conventional monomeric myoglobins, this group also has dimeric and unusual indoleamine dioxygenase-like myoglobins. We isolated myoglobin from the radular muscle of living gastropod mollusc Theliostyla albicilla. The myoglobin appeared to be present in an oxidized met-form, a physiologically inactive form that is not capable of binding oxygen. Under the same extraction conditions, myoglobins mainly of the physiologically active oxy-form have been isolated from other molluscs. The complete amino acid sequence of 157 residues of Theliostyla myoglobin shows that it has a long N-terminal extension of seven residues and contains three functional key residues: CD1-Phe, E7-His, and F8-His. The metmyoglobin can easily be reduced to a ferrous state with Na(2)S(2)O(4). The autoxidation rate of the oxy-form was comparable to other molluscan myoglobins over a wide pH range, and Theliostyla myoglobin was shown to be stable as an oxygen-binding protein. Thus, the predominantly met-form of myoglobin in Theliostyla can be attributed to the incomplete functioning of the myoglobin reduction system in the radular muscle. Although the function of Theliostyla myoglobin is unclear, it may be a scavenger of H(2)O(2).

Amino Acid Sequence↗
PubMed1991

Myoglobin depletes renal adenine nucleotide pools in the presence and absence of shock.

To assess whether myoglobin adversely affects renal adenylate pools, rats were infused with purified myoglobin (50 mg/100 g body wt) for two hours and renal ATP, ADP, and AMP levels were measured in the absence of shock, after 25 minutes of hemorrhagic shock (55 to 60 mm Hg) or 30 minutes post-recovery. In the absence of shock, myoglobin lowered ATP by 24% (assessed 65 min post-infusion) without affecting renal blood flow (RBF). This effect was completely blocked by deferoxamine (DFO) treatment and it could not be reproduced by ribonuclease infusion (a non-Fe containing, but filtered, protein). Myoglobin + shock caused a three- to fourfold greater decline in ATP than did shock alone despite comparable RBFs. Shock plus myoglobin, but neither one alone, induced substantial S1/S2 proximal tubular morphologic damage and a severe reduction in creatinine clearance, confirming synergistic injury. Ribonuclease completely reproduced myoglobin's effect on shock-induced adenylate profiles. DFO +/- hydroxyl radical scavenger therapy (Na benzoate) did not block the myoglobin shock effect on adenylate pools. Post-shock adenylate recovery was not compromised by myoglobin pre-treatment. If renal artery occlusion (RAO), rather than shock, was used as the ischemic challenge, myoglobin had no discernible impact on adenine nucleotide content. This study concludes that: 1) myoglobin modestly lowers baseline adenylate pools due to an Fe dependent mechanism; 2) myoglobin drastically accentuates shock-induced adenylate depletion by a non-hemodynamic/non-Fe dependent mechanism; 3) myoglobin nephrotoxicity cannot be attributed solely to tissue iron loading; and 4) the RAO model can completely mask important influences on ischemic cellular energetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed2003

Pyruvate attenuates myoglobin in vitro toxicity.

Myoglobinuria is a complication of crush injury as well as substance abuse. This study examined whether pyruvate modified myoglobin in vitro renal toxicity. Renal slices from Fischer-344 rats were incubated for 120 min with 0-12 mg/ml myoglobin. In an initial study, gluconeogenesis was stimulated by the addition of 10 mM pyruvate during the final 30 min. In all other studies, renal slices were incubated with myoglobin in the presence of 0 or 10 mM pyruvate for 120 min. Myoglobin increased lactate dehydrogenase (LDH) release and this was not modified by the presence of pyruvate for the last 30 min of the incubation. Myoglobin toxicity was reduced by coincubation of myoglobin with pyruvate for 120 min. LDH leakage was increased 1.2-, 1.7-, and 1.8-fold above control by 4, 10, and 12 mg/ml myoglobin, compared to 1.2, 1.3, and 1.3 fold in slices coincubated with 10 mM pyruvate, respectively. Myoglobin diminished adenosine triphosphate (ATP) levels but pyruvate maintained a 5x higher level of ATP within the slices. Glucose (10 mM) provided protection only for the low concentration (4 mg/ml) of myoglobin. Myoglobin induced oxidative stress while pyruvate prevented the rise in lipid peroxidation and glutathione disulfides by myoglobin. Myoglobin diminished total glutathione levels in pyruvate-treated tissue, but glutathione levels remained higher than tissues incubated in the absence of pyruvate. These results indicate that pyruvate reduced toxicity by preventing oxidative stress and via a supply of an energy substrate.

Adenosine Triphosphate↗
PubMed1992

Early diagnosis of acute myocardial infarction by a newly developed rapid immunoturbidimetric assay for myoglobin.

OBJECTIVE: To evaluate a rapid immunoturbidimetric assay for myoglobin and to investigate its clinical usefulness in the early detection of acute myocardial infarction. DESIGN: Prospective study. Immunoturbidimetrically determined myoglobin concentrations were compared with radioimmunoassay results obtained with the same blood samples. The diagnostic performance of myoglobin determination was compared with creatine kinase and creatine kinase MB activity (current standard of routine diagnosis). SETTINGS: Part 1: coronary care unit. Part 2: emergency room in a university hospital. PATIENTS: Part 1:30 patients with acute myocardial infarction admitted not later than four hours (median two hours) after the onset of symptoms. Part 2: 126 patients admitted to the emergency room with chest pain not caused by trauma (51 cases of acute myocardial infarction, 51 cases of angina pectoris, and 24 cases of chest pain not related to coronary artery disease). INTERVENTIONS: Part 1: routine treatment including intravenous thrombolytic treatment (28 patients). Part 2: routine emergency treatment without thrombolytic treatment. MAIN OUTCOME MEASURES: The analytical quality of the immunoturbidimetric myoglobin assay and a comparison between the myoglobin assay and creatine kinase and creatine kinase MB for diagnostic sensitivity and performance. RESULTS: The immunoturbidimetric myoglobin assay was fast and convenient and gave myoglobin determinations of high analytical quality. The concentration of myoglobin increased, peaked, and returned to the reference range significantly earlier than creatine kinase (p < or = 0.0001) and creatine kinase MB (p < or = 0.0002). Before thrombolytic therapy was started the diagnostic sensitivity of myoglobin was significantly higher than that of creatine kinase MB activity 0-6 h after the onset of chest pain and significantly higher (0.82 v 0.29) than creatine kinase 2-4 h after the onset of chest pain. In almost all patients (92%) plasma myoglobin concentrations were increased 4-6 h after the onset of chest pain. CONCLUSION: Myoglobin was more sensitive in detecting early myocardial infarction than creatine kinase and creatine kinase MB activity. Immunoturbidimetric myoglobin measurements could be useful in the early evaluation of patients with suspected myocardial infarction because this assay takes less than two minutes.

Clinical Enzyme Tests↗