Myoglobin

Myoglobin

Overview
Myoglobin is an iron- and oxygen-binding protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 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. The only time myoglobin is found in the bloodstream is when it is released following muscle injury. It is an abnormal finding, and can be diagnostically relevant when found in blood.
Myoglobin (abbreviated Mb) is a single-chain
Tertiary structure
In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...

 globular protein of 153 or 154 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s, containing a heme
Heme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...

 (iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...

-containing porphyrin
Porphyrin
Porphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at...

) prosthetic group in the center around which the remaining apoprotein
Apoprotein
Apoprotein can refer to:*Apoenzyme, the protein part of an enzyme without its characteristic prosthetic group.*Apolipoprotein, a lipid-binding protein that is a constituent of the plasma lipoprotein....

 folds.
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Encyclopedia
Myoglobin is an iron- and oxygen-binding protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 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. The only time myoglobin is found in the bloodstream is when it is released following muscle injury. It is an abnormal finding, and can be diagnostically relevant when found in blood.
Myoglobin (abbreviated Mb) is a single-chain
Tertiary structure
In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...

 globular protein of 153 or 154 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s, containing a heme
Heme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...

 (iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...

-containing porphyrin
Porphyrin
Porphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at...

) prosthetic group in the center around which the remaining apoprotein
Apoprotein
Apoprotein can refer to:*Apoenzyme, the protein part of an enzyme without its characteristic prosthetic group.*Apolipoprotein, a lipid-binding protein that is a constituent of the plasma lipoprotein....

 folds. It has eight alpha helices and a hydrophobic core. It has a molecular weight of 17,699 daltons
Atomic mass unit
The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...

 (with heme), and is the primary oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

-carrying pigment
Biological pigment
Biological pigments, also known simply as pigments or biochromes are substances produced by living organisms that have a color resulting from selective color absorption. Biological pigments include plant pigments and flower pigments...

 of muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...

 tissues. Unlike the blood-borne hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

, to which it is structurally related, this protein does not exhibit cooperative binding
Cooperative binding
In biochemistry, a macromolecule exhibits cooperative binding if its affinity for its ligand changes with the amount of ligand already bound.Cooperative binding is a special case of allostery. Cooperative binding requires that the macromolecule have more than one binding site, since cooperativity...

 of oxygen, since positive cooperativity is a property of multimeric/oligomeric
Oligomer
In chemistry, an oligomer is a molecule that consists of a few monomer units , in contrast to a polymer that, at least in principle, consists of an unlimited number of monomers. Dimers, trimers, and tetramers are oligomers. Many oils are oligomeric, such as liquid paraffin...

 proteins only. Instead, the binding of oxygen by myoglobin is unaffected by the oxygen pressure in the surrounding tissue. Myoglobin is often cited as having an "instant binding tenacity" to oxygen given its hyperbolic oxygen dissociation
Dissociation (chemistry)
Dissociation in chemistry and biochemistry is a general process in which ionic compounds separate or split into smaller particles, ions, or radicals, usually in a reversible manner...

 curve. High concentrations of myoglobin in muscle cells allow organisms to hold their breaths longer. Diving mammals such as whales and seals have muscles with particularly high myoglobin abundance.

Myoglobin was the first protein to have its three-dimensional structure revealed. In 1958, John Kendrew
John Kendrew
Sir John Cowdery Kendrew, CBE, FRS was an English biochemist and crystallographer who shared the 1962 Nobel Prize in Chemistry with Max Perutz; their group in the Cavendish Laboratory investigated the structure of heme-containing proteins.-Biography:He was born in Oxford, son of Wilford George...

 and associates successfully determined the structure of myoglobin by high-resolution X-ray crystallography
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...

. For this discovery, John Kendrew shared the 1962 Nobel Prize in chemistry
Nobel Prize in Chemistry
The Nobel Prize in Chemistry is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in chemistry, physics, literature,...

 with Max Perutz
Max Perutz
Max Ferdinand Perutz, OM, CH, CBE, FRS was an Austrian-born British molecular biologist, who shared the 1962 Nobel Prize for Chemistry with John Kendrew, for their studies of the structures of hemoglobin and globular proteins...

. Despite being one of the most studied proteins in biology, its true physiological function is not yet conclusively established: mice genetically engineered to lack myoglobin are viable, but showed a 30% reduction in cardiac systolic output. They adapted to this deficiency through hypoxic genetic mechanisms and increased vasodilation. In humans myoglobin is encoded by the MB gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.

Meat color



Myoglobin forms pigment
Pigment
A pigment is a material that changes the color of reflected or transmitted light as the result of wavelength-selective absorption. This physical process differs from fluorescence, phosphorescence, and other forms of luminescence, in which a material emits light.Many materials selectively absorb...

s responsible for making meat red
Red meat
Red meat in traditional culinary terminology is meat which is red when raw and not white when cooked. In the nutritional sciences, red meat includes all mammal meat. Red meat includes the meat of most adult mammals and some fowl ....

. The color that meat takes is partly determined by the oxidation states of the iron atom in myoglobin and the oxygen species attached to it. When meat is in its raw state, the iron atom is in the +2 oxidation state, and is bound to a dioxygen molecule (O2). Meat cooked well done
Well Done
Well Done is a mixtape by American rapper Tyga, released November 8, 2010, on Young Money Entertainment.- Reception :- Tracklist :...

 is brown because the iron atom is now in the +3 oxidation state, having lost an electron, and is now coordinated by a water molecule. Under some conditions, meat can also remain pink all through cooking, despite being heated to high temperatures. If meat has been exposed to nitrites, it will remain pink because the iron atom is bound to NO, nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...

 (true of, e.g., corned beef
Corned beef
Corned beef is a type of salt-cured beef products present in many beef-eating cultures. The English term is used interchangeably in modernity to refer to three distinct types of cured beef:...

 or cured ham
Ham
Ham is a cut of meat from the thigh of the hind leg of certain animals, especiallypigs. Nearly all hams sold today are fully cooked or cured.-Etymology:...

s). Grilled meats can also take on a pink "smoke ring
Smoke ring
A smoke ring is a visible vortex ring formed by sudden release of smoke. It can be created by blowing smoke from the mouth, quickly lighting a cigarette lighter and putting it out or holding a burning incense stick or a cigarette vertically, pushing it with the burning side up and suddenly pulling...

" that comes from the iron binding to a molecule of carbon monoxide to give metmyoglobin
Metmyoglobin
Metmyoglobin is the oxidised form of the oxygen-carrying protein myoglobin.Metmyoglobin is the cause of the characteristic brown colouration of meat that occurs as it ages....

. Raw meat packed in a carbon monoxide atmosphere also shows this same pink "smoke ring" due to the same coordination chemistry. 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 in the meat for a very long time, 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. 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.

Role in disease


Myoglobin is released from damaged muscle tissue (rhabdomyolysis
Rhabdomyolysis
Rhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...

), 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
Acute renal failure
Acute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...

. 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, lysozyme
Lysozyme
Lysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase, are glycoside hydrolases, enzymes that damage bacterial cell walls by catalyzing hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between...

s).

Myoglobin is a sensitive marker for muscle injury, making it a potential marker for heart attack
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...

 in patients with chest pain
Chest pain
Chest pain may be a symptom of a number of serious conditions and is generally considered a medical emergency. Even though it may be determined that the pain is non-cardiac in origin, this is often a diagnosis of exclusion made after ruling out more serious causes of the pain.-Differential...

. However, elevated myoglobin has low specificity for acute myocardial infarction (AMI)
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...

 and thus CK-MB
Creatine kinase
Creatine kinase , also known as creatine phosphokinase or phospho-creatine kinase , is an enzyme expressed by various tissues and cell types. CK catalyses the conversion of creatine and consumes adenosine triphosphate to create phosphocreatine and adenosine diphosphate...

, cTnT
Troponin
400px|thumb|right|alt = Colored dice with checkered background|Ribbon representation of the human cardiac troponin core complex in the calcium-saturated form...

, ECG
Electrocardiogram
Electrocardiography is a transthoracic interpretation of the electrical activity of the heart over a period of time, as detected by electrodes attached to the outer surface of the skin and recorded by a device external to the body...

, and clinical signs should be taken into account to make the diagnosis.

Structure and bonding


Myoglobin contains a porphyrin
Porphyrin
Porphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at...

 ring with an iron center. There is a proximal histidine
Histidine
Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...

group attached directly to the iron center, and a distal histidine group on the opposite face, not bonded to the iron.

Many functional models of myoglobin have been studied. One of the most important is that of picket fence porphyrin by James Collman. This model was used to show the importance of the distal prosthetic group. It serves three functions:
  1. To form hydrogen bond
    Hydrogen bond
    A hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom, such as nitrogen, oxygen or fluorine, that comes from another molecule or chemical group. The hydrogen must be covalently bonded to another electronegative atom to create the bond...

    s with the dioxygen moiety, increasing the O2 binding constant
  2. To prevent the binding of carbon monoxide
    Carbon monoxide
    Carbon monoxide , also called carbonous oxide, is a colorless, odorless, and tasteless gas that is slightly lighter than air. It is highly toxic to humans and animals in higher quantities, although it is also produced in normal animal metabolism in low quantities, and is thought to have some normal...

    , whether from within or without the body. Carbon monoxide binds to iron in an end-on fashion, and is hindered by the presence of the distal histidine
    Histidine
    Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...

    , which forces it into a bent conformation. CO binds to heme 23,000 times better than O2, but only 200 times better in hemoglobin
    Hemoglobin
    Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

     and myoglobin. Oxygen binds in a bent fashion, which can fit with the distal histidine.
  3. To prevent irreversible dimer
    Protein dimer
    In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...

    ization of the oxymyoglobin with another deoxymyoglobin species

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