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. 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 and a widening of blood vessels. In humans myoglobin
is encoded by the MB gene.
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
a dioxygen molecule. Meat cooked well done is brown because the iron atom is now in the
ferric 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. 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, 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. It is not the myoglobin itself that is toxic
but the ferrihemate portion that is dissociated from myoglobin in acidic environments.
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 and thus CK-MB, cTnT, ECG, and clinical signs should be taken
into account to make the diagnosis. Structure and bonding
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
is attached directly to iron, and a distal histidine group 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,
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 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.
See also Cytoglobin
Hemoglobin Hemoprotein
Neuroglobin References
Further reading
External links The Myoglobin Protein
Protein Database featured molecule Online 'Mendelian Inheritance in Man' 160000
human genetics Which Cut Is Older? 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. Mirceta, S.; Signore, A. V.; Burns, J. M.;
Cossins, A. R.; Campbell, K. L.; Berenbrink, M.. "Evolution of Mammalian Diving Capacity
Traced by Myoglobin Net Surface Charge". Science 340: 1234192. doi:10.1126/science.1234192.
PMID 23766330. . Also see Proteopedia article about this finding