Myoglobin From Wikipedia, the free encyclopedia Myoglobin Myoglobin.png Model of helical domains in myoglobin.[1] Available structures PDB Ortholog search: PDBe, RCSB [show]List of PDB id codes Identifiers Symbols MB ; PVALB External IDs OMIM: 160000 MGI: 96922 HomoloGene: 3916 GeneCards: MB Gene [show]Gene ontology RNA expression pattern PBB GE MB 204179 at tn.png 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] This box: view talk edit 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. Myoglobin is only found in the bloodstream after muscle injury. It is an abnormal finding, and can be diagnostically relevant when found in blood. [2] Myoglobin is the primary oxygen-carrying pigment of muscle tissues.[3] 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.[2] 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.[4] This achievement was reported in 1958 by John Kendrew and associates.[5] For this discovery, John Kendrew shared the 1962 Nobel Prize in chemistry with Max Perutz.[6] 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).[7] In humans myoglobin is encoded by the MB gene.[8] Contents [hide] 1 Meat color 2 Role in disease 3 Structure and bonding 4 Synthetic analogues 5 See also 6 References 7 Further reading 8 External links Meat color[edit] 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 a dioxygen 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.[9] 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.[10] 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.[11] Role in disease[edit] 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 renal failure.[12] 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.[13] 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[edit] Molecular orbital description of Fe-O2 interaction in myoglobin.[14] 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.[15] 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.[15] 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. Synthetic analogues[edit] 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.[16] 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.[17]