Myoglobin

Myoglobin
Model of helical domains in myoglobin.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3RGK
Identifiers
Symbols	MB ; PVALB
External IDs	OMIM: 160000 MGI: 96922 HomoloGene: 3916 GeneCards: MB Gene
Gene ontology Molecular function • oxygen transporter activity • iron ion binding • oxygen binding • heme binding Biological process • response to hypoxia • heart development • response to hormone stimulus • slow-twitch skeletal muscle fiber contraction • response to hydrogen peroxide • enucleate erythrocyte differentiation • brown fat cell differentiation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4151	17189
Ensembl	ENSG00000198125	ENSMUSG00000018893
UniProt	P02144	P04247
RefSeq (mRNA)	NM_005368	NM_001164047
RefSeq (protein)	NP_005359	NP_001157519
Location (UCSC)	Chr 22: 36 – 36.03 Mb	Chr 15: 77.02 – 77.05 Mb
PubMed search	[1]	[2]

Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to hemoglobin, which is the iron- and oxygen-binding protein in blood, specifically in the red blood cells. In humans, myoglobin is only found in the bloodstream after muscle injury. It is an abnormal finding, and can be diagnostically relevant when found in blood.

Myoglobin is the primary oxygen-carrying pigment of muscle tissues. 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. Myoglobin is found in Type I muscle, Type II A and Type II B, but most texts consider myoglobin not to be found in smooth muscle.

Myoglobin was the first protein to have its three-dimensional structure revealed by X-ray crystallography. This achievement was reported in 1958 by John Kendrew and associates. For this discovery, John Kendrew shared the 1962 Nobel Prize in chemistry with Max Perutz. Despite being one of the most studied proteins in biology, its physiological function is not yet conclusively established: mice genetically engineered to lack myoglobin are viable, but showed a 30% reduction in volume of blood being pumped by the heart during a contraction. They adapted to this deficiency through natural reactions to inadequate oxygen supply (hypoxia) and a widening of blood vessels (vasodilation). In humans myoglobin is encoded by the MB gene.

Differences from hemoglobin

Myoglobin is similar to hemoglobin in that it is involved in the transportation of oxygen to cells. There are many distinct differences that set the protein apart from hemoglobin. For one the protein has only one binding site for oxygen on the one heme group on the protein. While myoglobin can only hold one oxygen, the affinity for that oxygen is very high compared to hemoglobin. This is likely due to the fact that hemoglobin, transporting 4 oxygens to the tissues and muscles where myoglobin is mostly present. The myoglobin takes the oxygen from the hemoglobin (due to the Bohr Effect) and takes that oxygen to muscle cells for use in metabolic processes.

Meat color

Myoglobin contains hemes, pigments responsible for the color of red meat. The color that meat takes is partly determined by the degree of oxidation of the myoglobin. In fresh meat the iron atom is the ferrous 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 pink "smoke ring" that comes from the iron binding to a molecule of carbon monoxide. 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. Hormel and Cargill are both reported to use this meat-packing process, and meat treated this way has been in the consumer market since 2003.

Role in disease

Myoglobin is released from damaged muscle tissue (rhabdomyolysis), which has very high concentrations of myoglobin. The released myoglobin is filtered by the kidneys but is toxic to the renal tubular epithelium and so may cause Acute kidney injury. 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. However, elevated myoglobin has low specificity for acute myocardial infarction (AMI) and thus CK-MB, cTnT, ECG, and clinical signs should be taken into account to make the diagnosis.

Structure and bonding

Molecular orbital description of Fe-O₂ interaction in myoglobin.

Myoglobin belongs to the globin superfamily of proteins, and as with other globins, consists of eight alpha helices connected by loops. Human globin contains 154 amino acids.

Myoglobin contains a porphyrin ring with an iron at its center. A proximal histidine group (His-94) is attached directly to iron, and a distal histidine group (His-65) hovers near the opposite face. 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.

The heme group in myoglobin can also bind nitric oxide (NO) with a 10-fold higher affinity than CO. Detachment of NO can be triggered by photoexcitation with 15 nm light pulse, causing the formation of several intermediate species.

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. 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.

A picket-fence porphyrin complex of Fe, with axial coordination sites occupied by methylimidazole (green) and dioxygen. The R groups flank the O₂-binding site.

See also

• Cytoglobin
• Hemoglobin
• Hemoprotein
• Neuroglobin

Further reading

• . Also see Proteopedia article about this finding

External links

• Online 'Mendelian Inheritance in Man' (OMIM) 160000 human genetics
• The Myoglobin Protein
• Protein Database featured molecule
• Which Cut Is Older? (It's a Trick Question) New York Times, February 21, 2006 article regarding meat industry use of carbon monoxide to keep meat looking red.
• Stores React to Meat Reports New York Times, March 1, 2006 article on the use of carbon monoxide to make meat appear fresh.