Myoglobin

MB
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3RGK
Identifiers
Aliases	MB, PVALB, myoglobgin, myoglobin, Myoglobin
External IDs	OMIM: 160000 MGI: 96922 HomoloGene: 3916 GeneCards: MB
Gene location (Human) Chr. Chromosome 22 (human)[1] Band 22q12.3 Start 35,606,764 bp[1] End 35,637,951 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15 D3|15 36.36 cM Start 76,899,687 bp[2] End 76,934,870 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right ventricle gastrocnemius muscle triceps brachii muscle body of tongue biceps brachii myocardium deltoid muscle tibialis anterior muscle thoracic diaphragm quadriceps femoris muscle Top expressed in digastric muscle soleus muscle right ventricle intercostal muscle temporal muscle ankle myocardium of ventricle sternocleidomastoid muscle interventricular septum cardiac muscles More reference expression data BioGPS More reference expression data
Gene ontology Molecular function oxygen binding heme binding metal ion binding oxygen carrier activity Cellular component extracellular exosome cytosol Biological process response to hormone heart development slow-twitch skeletal muscle fiber contraction response to hypoxia enucleate erythrocyte differentiation response to hydrogen peroxide brown fat cell differentiation oxygen transport transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4151 17189 Ensembl ENSG00000198125 ENSMUSG00000018893 UniProt P02144 P04247 RefSeq (mRNA) NM_005368 NM_203377 NM_203378 NM_001362846 NM_001164047 NM_001164048 NM_013593 RefSeq (protein) NP_005359 NP_976311 NP_976312 NP_001349775 NP_001369738 NP_001369739 NP_001369740 NP_001369741 NP_001369742 NP_001157519 NP_001157520 NP_038621 Location (UCSC) Chr 22: 35.61 – 35.64 Mb Chr 15: 76.9 – 76.93 Mb PubMed search [3] [4]
Wikidata
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Myoglobin (symbol Mb or MB) is an iron- and oxygen-binding protein found in the cardiac and skeletal muscle tissue of vertebrates in general and in almost all mammals.^{[5][6][7][8][9]} Myoglobin is distantly related to hemoglobin. Compared to hemoglobin, myoglobin has a higher affinity for oxygen and does not have cooperative binding with oxygen like hemoglobin does.^[8][10] Myoglobin consists of non-polar amino acids at the core of the globulin, where the heme group is non-covalently bounded with the surrounding polypeptide of myoglobin. In humans, myoglobin is found in the bloodstream only after muscle injury.^[11][12][13]

High concentrations of myoglobin in muscle cells allow organisms to hold their breath for a longer period of time. Diving mammals such as whales and seals have muscles with particularly high abundance of myoglobin.^[13] Myoglobin is found in Type I muscle, Type II A, and Type II B; although many older texts describe myoglobin as not found in smooth muscle, this has proved erroneous: there is also myoglobin in smooth muscle cells.^[14]

Myoglobin was the first protein to have its three-dimensional structure revealed by X-ray crystallography.^[15] This achievement was reported in 1958 by John Kendrew and associates.^[16] For this discovery, Kendrew shared the 1962 Nobel Prize in chemistry with Max Perutz.^[17][18] Despite being one of the most studied proteins in biology, its physiological function is not yet conclusively established: mice genetically engineered to lack myoglobin can be viable and fertile, but show many cellular and physiological adaptations to overcome the loss. Through observing these changes in myoglobin-depleted mice, it is hypothesised that myoglobin function relates to increased oxygen transport to muscle, and to oxygen storage; as well, it serves as a scavenger of reactive oxygen species.^[19]

In humans, myoglobin is encoded by the MB gene.^[20]

Myoglobin can take the forms oxymyoglobin (MbO₂), carboxymyoglobin (MbCO), and metmyoglobin (met-Mb), analogously to hemoglobin taking the forms oxyhemoglobin (HbO₂), carboxyhemoglobin (HbCO), and methemoglobin (met-Hb).^[21]

Differences from hemoglobin

Like hemoglobin, myoglobin is a cytoplasmic protein that binds oxygen on a heme group. It harbors only one globulin group, whereas hemoglobin has four. Although its heme group is identical to those in Hb, Mb has a higher affinity for oxygen than does hemoglobin but fewer total oxygen-storage capacities.^[22] The newest discovery reveals that myoglobin facilitates oxygen diffusion down a gradient, enhancing oxygen transport in mitochondria.

Role in cuisine

Myoglobin contains hemes, pigments responsible for the colour of red meat. The colour that meat takes is partly determined by the degree of oxidation of the myoglobin. In fresh meat the iron atom is in the ferrous (+2) oxidation state bound to an oxygen molecule (O₂). Meat cooked well done is brown because the iron atom is now in the ferric (+3) oxidation state, having lost an electron. If meat has been exposed to nitrites, it will remain pink, because the iron atom is bound to NO, nitric oxide (true of, e.g., corned beef or cured hams). Grilled meats can also take on a reddish pink "smoke ring" that comes from the heme center binding to carbon monoxide.^[23] Raw meat packed in a carbon monoxide atmosphere also shows this same pink "smoke ring" due to the same principles. Notably, the surface of this raw meat also displays the pink color, which is usually associated in consumers' minds with fresh meat. This artificially induced pink color can persist, reportedly up to one year.^[24] Hormel and Cargill (meat processing companies in the US) are both reported to use this meat-packing process, and meat treated this way has been in the consumer market since 2003.^[25]

Meat alternatives have used various ways to recreate the "meaty" taste associated with myoglobin. Impossible Foods uses leghemoglobin, a heme-containing globin from soy root nodule, produced as a recombinant protein in Komagataella ("Pichia pastoris") yeast.^[26][27] Motif FoodWorks produces a recombinant bovine myoglobin using Komagataella yeast,^[28] considered GRAS by the FDA.^[29] Moolec Science has engineered a soybean that produces procine myoglobin in its seeds called "Piggy Sooy"; it was approved by the USDA in April 2024.^[30]

Role in disease

Myoglobin is released from damaged muscle tissue, which contain very high concentrations of myoglobin.^[31] The released myoglobin enters the bloodstream, where high levels lead to rhabdomyolysis. The myoglobin is filtered by the kidneys, but is toxic to the renal tubular epithelium and so may cause acute kidney injury.^[32] It is not the myoglobin itself that is toxic (it is a protoxin), but the ferrihemate portion that is dissociated from myoglobin in acidic environments (e.g., acidic urine, lysosomes).

Myoglobin is a sensitive marker for muscle injury, making it a potential marker for heart attack in patients with chest pain.^[33] However, elevated myoglobin has low specificity for acute myocardial infarction (AMI) and thus CK-MB, cardiac troponin, ECG, and clinical signs should be taken into account to make the diagnosis.^[34]

Structure and bonding

Myoglobin belongs to the globin superfamily of proteins, and as with other globins, consists of eight alpha helices connected by loops. Myoglobin contains 153 amino acids.^[35]

Myoglobin contains a porphyrin ring with an iron at its center. A proximal histidine group (His-93) is attached directly to iron, and a distal histidine group (His-64) hovers near the opposite face.^[35] The distal imidazole is not bonded to the iron, but is available to interact with the substrate O₂. This interaction encourages the binding of O₂, but not carbon monoxide (CO), which still binds about 240× more strongly than O₂.

The binding of O₂ causes substantial structural change at the Fe center, which shrinks in radius and moves into the center of N4 pocket. O₂-binding induces "spin-pairing": the five-coordinate ferrous deoxy form is high spin and the six coordinate oxy form is low spin and diamagnetic.^{[citation needed]}

• 
  Molecular orbital description of Fe-O₂ interaction in myoglobin.^[36]
• 
  This is an image of an oxygenated myoglobin molecule. The image shows the structural change when oxygen is bound to the iron atom of the heme prosthetic group. The oxygen atoms are colored in green, the iron atom is colored in red, and the heme group is colored in blue.
• 
  Myoglobin

Synthetic analogues

Many models of myoglobin have been synthesized as part of a broad interest in transition metal dioxygen complexes. A well known example is the picket fence porphyrin, which consists of a ferrous complex of a sterically bulky derivative of tetraphenylporphyrin.^[37] In the presence of an imidazole ligand, this ferrous complex reversibly binds O₂. The O₂ substrate adopts a bent geometry, occupying the sixth position of the iron center. A key property of this model is the slow formation of the μ-oxo dimer, which is an inactive diferric state. In nature, such deactivation pathways are suppressed by protein matrix that prevents close approach of the Fe-porphyrin assemblies.^[38]

See also

• Cytoglobin
• Hemoglobin
• Hemoprotein
• Neuroglobin
• Phytoglobin
• Myoglobinuria - The presence of myoglobin in the urine
• Ischemia-reperfusion injury of the appendicular musculoskeletal system

References

Further reading

External links

• Online Mendelian Inheritance in Man (OMIM): 160000 human genetics
• The Myoglobin Protein
• RCSB PDB featured molecule
• "Which Cut Is Older? (It's a Trick Question)", The New York Times, February 21, 2006 article regarding meat industry use of carbon monoxide to keep meat looking red.
• "Stores React to Meat Reports", The New York Times, March 1, 2006 article on the use of carbon monoxide to make meat appear fresh.
• Overview of all the structural information available in the PDB for UniProt: P02144 (Human Myoglobin) at the PDBe-KB.