Search databaseBooksAll DatabasesAssemblyBiocollectionsBioProjectBioSampleBioSystemsBooksClinVarConserved DomainsdbGaPdbVarGeneGenomeGEO DataSetsGEO ProfilesGTRHomoloGeneIdentical Protein GroupsMedGenMeSHbromheads.tv web Sitebromheads.tv CatalogNucleotideOMIMPMCPopSetProteinProtein ClustersProtein family ModelsPubChem BioAssayPubChem CompoundPubChem SubstancePubMedSNPSRAStructureTaxonomyToolKitToolKitAllToolKitBookgh

bromheads.tv Bookshelf. A service of the nationwide Library the Medicine, nationwide Institutes that Health.

You are watching: Myoglobin ________

StatPearls . Treasure Island (FL): StatPearls Publishing; 2021 Jan-.


*

Introduction

Myoglobin is a protein located primarily in the striated muscles of vertebrates. MB is the gene encoding myoglobin in humans. That encodes a single polypeptide chain with one oxygen binding site. Myoglobin consists of a heme prosthetic group that have the right to reversibly tie to oxygen. The body provides it as an oxygen warehouse protein in muscle. That is able come bind and release oxygen depending upon the oxygen concentration in the cell. Its major function, as a result, is to supply oxygen come myocytes. Myoglobin likewise functions in the hemostasis the nitric oxide. It additionally plays a function in the detoxification of reactive oxygen species. Myoglobin is the factor for the red color of the muscle of most vertebrates.<1><2>


Fundamentals

Myoglobin is among the members the the globin superfamily, which additionally includes hemoglobin. It regularly gets compared structurally and also functionally to hemoglobin. Hemoglobin has 4 polypeptide chains and also four oxygen binding sites. Myoglobin is a single polypeptide chain through one oxygen binding site, which results in the different binding kinetics of the two proteins to oxygen. Myoglobin does for this reason noncooperatively, unlike hemoglobin which binding to oxygen cooperatively as a an outcome of the tetrameric nature. As a result, myoglobin’s oxygen saturation curve is hyperbolic. Hemoglobin displays a sigmoid-shaped curve due to its participating binding. Myoglobin exhibits a greater affinity because that oxygen 보다 hemoglobin. Therefore, it is really efficient at extracting oxygen indigenous the blood. Myoglobin is mainly existing in the striated muscle of vertebrates. Hemoglobin, top top the various other hand, is discovered in the bloodstream together a part of erythrocytes. Myoglobin is likewise present in much lower concentrations in smooth muscle, endothelial, and also even tumor cells.<1><2>


Issues of Concern

Myoglobin’s role as a marker because that a disease is limited. That is no much longer in particular guidelines for the monitoring of acute coronary syndromes. With regards to rhabdomyolysis, myoglobin is no a prognostic criterion and also is no diagnostic.<3>


Cellular

Myoglobin occurs in the highest possible concentration in the striated muscles of vertebrates. Specifically, the is in the cytoplasm of cardiac myocytes and the sarcoplasm the oxidative bones muscle fibers; this includes skeletal muscle and heart muscle. Myoglobin is likewise present in much reduced concentrations in smooth muscle and also endothelial tumor cells.<2>

The expression the the MB gene has additionally been reported in various tumor cell lines such as chest carcinoma, colon carcinoma, acute leukemia, desmoplastic little round cabinet tumors, and non-small cabinet lung cancer.<4>


Molecular

Myoglobin is a solitary polypeptide chain of 154 amino acids. The chain consists of eight α-helices assigned the letters A–H. The molecule has a heme prosthetic group, which consists of a porphyrin ring stole ion. The heme-bound Fe cation have the right to exist in the 2+ (reduced) or 3+ (oxidized) state. The stole ion chin interacts v six various ligands, among which serves together the binding website for oxygen. This binding site can also duty to bind other potential molecules, consisting of CO and NO.<1>


Function

The primary role of myoglobin is to supply oxygen to the muscle. That does this by publication its oxygen supply to the mitochondria that consist of the respiratory tract chain, helping the myocytes to satisfy their high energy demands. Myoglobin serves together a buffer that intracellular oxygen concentrations and as an oxygen reservoir in muscle. This ide has support from the fact that diving mammals deserve to have 10- to 30-fold more myoglobin as compared to pets that perform not organize their breath for an extended period.<1>

Myoglobin facilitates oxygen diffusion. Myoglobin desaturates in ~ the start of muscle activity, which increases oxygen’s diffusion gradient native the capillaries come the cytoplasm.

Myoglobin has also been displayed to have enzymatic functions. It is necessary for the decomposition the bioactive nitric oxide come nitrate. The removed of nitric oxide boosts mitochondrial respiration. This improvement is due to the fact that nitric oxide reversibly inhibits cytochrome oxidase.

Myoglobin, furthermore, functions to remove reactive oxygen species. It have the right to do this by communicating with fatty acids, which may be metabolically necessary under oxygenated conditions and high power demands.<2>


Mechanism

Myoglobin consists of a Fe(II) cation bound to a heme group, which provides it the capability to bind to oxygen reversibly. Oxygen have the right to bind to the heme residue that myoglobin as result of the stole ion’s communication with six ligands. 4 of this ligands room nitrogens that with each other make a porphyrin ring and share a common aircraft with the iron. The 5th ligand is the imidazole next chain that His93 that stabilizes the heme group and slightly displaces the iron ion far from the plane. The sixth ligand position is the binding site for oxygen. As soon as oxygen binds to the iron ion, it partially pulls earlier to the aircraft of the porphyrin ring. Myoglobin can additionally bind alternating ligands such together CO, nitrite, and azide molecules. For example, CO binding strongly to myoglobin just as it does to hemoglobin, which develops carboxymyoglobin.<1>

In its decreased form, Fe(II), myoglobin have the right to either it is in bound to oxygen (oxymyoglobin) or not (deoxymyoglobin). Additionally, the stole ion can be oxidized to kind Fe(III), which is recognized as metmyoglobin. The binding of oxygen is excellent noncooperatively due to the fact that myoglobin is monomeric.<5> This binding is why myoglobin’s oxygen saturation curve is hyperbolic and characteristic of common Michaelis-Menten enzyme kinetics. The sigmoid form of the hemoglobin oxygen saturation curve is as result of its tetrameric makeup and cooperative binding of oxygen.


Testing

Myoglobin testing can happen in the blood or urine. The key indications for checking this lab space for rhabdomyolysis or myocardial infarction. As stated above, the usefulness of these tests is questionable.

With regards to rhabdomyolysis, myoglobin testing in the urine can be from the mix of a pee dipstick and also microscopy. In this an illness process, you will acquire a optimistic urine dipstick test for blood. However, once one looks in ~ the sample under the microscope, there will certainly be no evidence of red blood cells. The to pee dipstick reflects a false hopeful for blood due to the fact that myoglobin likewise reacts through the orthotolidine check reagent. Serum myoglobin is not important for diagnosing or managing rhabdomyolysis. To pee myoglobin is likewise not provided routinely.<6> A urinalysis deserve to reliably guess the lack of myoglobinuria. This test can be used instead of obtaining urine myoglobin.<7>

Additionally, myoglobin is a perceptible marker for acute myocardial infarction. However, it lacks specificity. The usefulness come in evaluating infarct size and also reperfusion. Myoglobin gets promptly released native the myocardium throughout the injury, and also its blood concentration rises in the 30 minutes immediately after the onset of the event. It is among the earliest markers to rise as the an outcome of ischemic heart disease. The is then promptly excreted by the kidneys in ~ 24 hours. In this sense, it is an essential marker for beforehand detection or exemption of cardiac damage. In summary, the usage of this biomarker because that myocardial infarction should be in combination with various other criteria in favor of diagnosing myocardial infarction. In current emergency room settings, myoglobin is not part of the diagnostic criteria. Troponins, Hs-cTnI and hs-cTnT, room the gold traditional biomarkers currently.<8>


Pathophysiology

Myoglobin knockout models have been created to try to understand its functions more clearly. Mice models have actually mutated myoglobin come the point of it being undetectable in cardiac and also skeletal muscle. The mutation causes several lethal cardiovascular defects in embryos. However, the mice who endured that stage of development exhibited cellular and also molecular adaptive responses to resolve the absence of myoglobin. These had having a greater capillary density in the heart to boost oxygen supply. Your results, in addition to other comparable studies, suggest that return compensatory responses exist, myoglobin is crucial for common muscle development and function.<9>

Myoglobin additionally plays a duty in the pathophysiology that rhabdomyolysis. The procedure begins with injury to the myocyte membrane or transformed energy production; this leader to an influx of extracellular calcium from in addition to a release of calcium native the sarcoplasmic reticulum and mitochondria from inside of the cell.  The accumulation of overabundance intracellular calcium reasons destructive processes bring about lysis the the cell and release of its contents, including myoglobin. This protein is the primary constituent the muscle the contributes to renal damage. The an initial proposed mechanism of that toxicity is tubular obstruction. Myoglobin deserve to precipitate the end of equipment in the renal tubules. This is exacerbated by intravascular volume depletion and also acidosis. The 2nd mechanism is through oxidant injury. Iron in myoglobin have the right to dissociate and also lead to the relax of complimentary radicals and also oxidative damage to the renal parenchyma. The final mechanism is through myoglobin inducing lipid peroxidation. This process creates molecules the act together vasoconstrictors come the renal arterioles.<10>


Clinical Significance

Myoglobin’s main clinical meaning comes v its association v muscle damage. In particular, it correlates with rhabdomyolysis and myocardial infarction. These are not disease processes result from defective myoglobin however rather persons that reason myoglobin to leak into the blood and urine, bring about damage. Rhabdomyolysis tote associations with myoglobinuria and often acute kidney injury. The first description that rhabdomyolysis remained in association v crush injuries and trauma. However, in hospitalized patients, more common causes include over-the-counter, prescription, and illicit drug use and also alcohol use. Seizures can also cause rhabdomyolysis.<11> Excessive myoglobin excretion in the pee can cause the color to readjust to red or brown. Liquid resuscitation is the main treatment to treat the acute kidney injury caused by myoglobin.<10>

Myoglobin is additionally detectable in the urine together the an outcome of hereditary myopathies. A muscle biopsy have the right to be excellent to determine these if performed after the illustration of rhabdomyolysis motivated by exercise. The diagnostic check of choice, however, is molecule genetics.<12>

Myoglobin is detectable in the serum after ~ acute myocardial infarction. However, as explained above, it is not right now in the guidelines because that diagnosis. It is one of the more quickly cardiac biomarkers to increase in concentration in the blood following myocardial infarction.<8>


Ordway GA, Garry DJ. Myoglobin: crucial hemoprotein in striated muscle. J Exp Biol. 2004 Sep;207(Pt 20):3441-6.
Koch J, Lüdemann J, Spies R, critical M, Amemiya CT, Burmester T. Inexplicable Diversity the Myoglobin gene in the Lungfish. Mol Biol Evol. 2016 Dec;33(12):3033-3041.
Servonnet A, Dubost C, boy name G, Lefrère B, Fontan E, Ceppa F, Delacour H. Ann Biol Clin (Paris). 2018 Apr 01;76(2):137-141.
Bicker A, Dietrich D, Gleixner E, Kristiansen G, Gorr TA, Hankeln T. Substantial transcriptional complexity during hypoxia-regulated expression the the myoglobin gene in cancer. Hum Mol Genet. 2014 january 15;23(2):479-90.
Silverstein TP, Kirk SR, Meyer SC, Holman KL. Myoglobin structure and function: A multiweek biochemistry activities project. Biochem Mol Biol Educ. 2015 May-Jun;43(3):181-8.
Sauret JM, Marinides G, Wang GK. Rhabdomyolysis. Am Fam Physician. 2002 Mar 01;65(5):907-12.
Schifman RB, Luevano DR. Value and Use of Urinalysis because that Myoglobinuria. Arch Pathol lab Med. 2019 Nov;143(11):1378-1381.
Aydin S, Ugur K, Aydin S, Sahin İ, Yardim M. Biomarkers in acute myocardial infarction: existing perspectives. Vasc health and wellness Risk Manag. 2019;15:1-10.
Meeson AP, Radford N, Shelton JM, Mammen PP, DiMaio JM, Hutcheson K, Kong Y, Elterman J, Williams RS, Garry DJ. Adaptive mechanisms that maintain cardiac duty in mouse without myoglobin. Circ Res. 2001 Apr 13;88(7):713-20.
10.
Zimmerman JL, Shen MC. Rhabdomyolysis. Chest. 2013 Sep;144(3):1058-1065.
11.

See more: Foods Labeled &Quot;Fat Free&Quot; Can Actually Contain Less Than 0.5 Grams Of Fat.


Zutt R, valve der Kooi AJ, Linthorst GE, Wanders RJ, de Visser M. Rhabdomyolysis: testimonial of the literature. Neuromuscul Disord. 2014 Aug;24(8):651-9.
Barca E, Emmanuele V, DiMauro SB. Metabolic Myoglobinuria. Curr Neurol Neurosci Rep. 2015 Oct;15(10):69.

This book is dispersed under the terms of the an imaginative Commons Attribution 4.0 worldwide License (http://creativecommons.org/licenses/by/4.0/), which patent use, duplication, adaptation, distribution, and reproduction in any type of medium or format, as long as friend give proper credit to the original author(s) and the source, a link is provided to the creative Commons license, and also any changes made are indicated.