myoglobin, protein molecule isolated from the cells of vertebrate skeletal muscle that is both a structural and functional relative of hemoglobin, the oxygen-transport protein of the blood of higher animals. Myoglobin, which is composed of a single polypeptide chain of 153 amino acid residues, has the ability to store oxygen by binding it to an iron atom; iron is part of myoglobin's essential chemical composition. The complete amino acid sequence of myoglobin has been determined; it is a relatively small protein with a molecular weight of approximately 17,000 grams per mole. The distribution of myoglobin among the higher animals is a reflection of its physiological function. It is found abundantly in the tissues of diving mammals, e.g., the whale, the seal, and the dolphin. High concentrations of myoglobin in these animals presumably allows them to store sufficient oxygen to remain underwater for long periods. Myoglobin is found abundantly in man only in cardiac muscle, which, by virtue of its essential function, must possess the capacity for continued activity when environmental oxygen concentrations are low. Myoglobin has been investigated intensely and is the first protein molecule to have been completely described in terms of its three-dimensional geometry. This achievement won the British scientist John Kendrew a share in the 1962 Nobel Prize for Chemistry.

Myoglobin is a single-chain globular protein of 153 amino acids, containing a heme (iron-containing porphyrin) prosthetic group in the center around which the remaining apoprotein folds. It has eight alpha helices and a hydrophobic core. It has a molecular weight of 16,700 daltons, and is the primary oxygen-carrying pigment of muscle tissues. Unlike the blood-borne hemoglobin, to which it is structurally related, this protein does not exhibit cooperative binding of oxygen, since positive cooperativity is a property of multimeric/oligomeric 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 curve. High concentrations of myoglobin in muscle cells allow organisms to hold their breaths longer. In 1958, John Kendrew and associates successfully determined the structure of myoglobin by high-resolution X-ray crystallography. For this discovery, John Kendrew shared the 1962 Nobel Prize in chemistry with Max Perutz. The human version of this gene is MB. 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 and show no obvious defects.

Meat color

Myoglobin forms pigments responsible for making meat red. The color that meat takes is partly determined by the charge of the iron atom in myoglobin and the oxygen attached to it. When meat is in its raw state, the iron atom has a charge of +2 and is bound to O₂, an oxygen molecule. Meat cooked well done is brown because the iron atom has a charge of +3, having lost an electron, and is now bound to a water molecule (H₂O). 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 (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 a molecule of carbon monoxide. Raw meat packed in a carbon monoxide atmosphere also shows this same pink "smoke ring" due to the same molecular process. Notably, the surface of the 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), 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.

Myoglobin is a sensitive marker for muscle injury, making it a potential marker for heart attack in patients with chest pain. CK-MB and cTnT is used in combination with ECG, and the clinical signs to diagnose Acute Myocardial Infarction (AMI).

Structure and bonding

Myoglobin contains a porphyrin ring with an iron center. There is a proximal histidine 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 bonds with the dioxygen moiety, increasing the O₂ binding constant
2. To prevent the binding of carbon monoxide, 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, which forces it into a bent conformation. CO binds to heme 23,000 times better than O₂, but only 200 times better in hemoglobin and myoglobin. Oxygen binds in a bent fashion, which can fit with the distal histidine.
3. To prevent irreversible dimerization of the oxymyoglobin with another deoxymyoglobin species

See also

• Hemoglobin
• Neuroglobin
• Cytoglobin
• Hemoprotein

References

Further reading

• J. P. Collman, R. Boulatov, C. J. Sunderland and L. Fu (2004). "Functional Analogues of Cytochrome c Oxidase, Myoglobin, and Hemoglobin". Chem. Rev. 104 (2): 561–588.
• Reeder, BJ; Svistunenko DA, Cooper CE, Wilson MT (2004). "The radical and redox chemistry of myoglobin and hemoglobin: from in vitro studies to human pathology". Antioxid Redox Signal 6 (6): 954–66.
• Schlieper, G; Kim JH, Molojavyi A, Jacoby C, Laussmann T, Flogel U, Godecke A, Schrader J (2004). "Adaptation of the myoglobin knockout mouse to hypoxic stress". Am J Physiol Regul Integr Comp Physiol 286 (4): R786–92.
• Takano, T (1977). "Structure of myoglobin refined at 2-0 A resolution. II. Structure of deoxymyoglobin from sperm whale". J. Mol. Biol. 110 569–584.
• Roy, A; Sen S, Chakraborti AS (2004). "In vitro nonenzymatic glycation enhances the role of myoglobin as a source of oxidative stress". Free Radic Res. 38 (2): 139–46.
• Stewart, JM; Blakely JA, Karpowicz PA, Kalanxhi E, Thatcher BJ, Martin BM (2004). "Unusually weak oxygen binding, physical properties, partial sequence, autoxidation rate and a potential phosphorylation site of beluga whale (Delphinapterus leucas) myoglobin". Comp Biochem Physiol B Biochem Mol Biol 137 (3): 401–12.
• Wu, G; Wainwright LM, Poole RK (2003). "Microbial globins". Adv Microb Physiol 47 255–310.

External links

• The Myoglobin Protein
• Protein Database featured molecule
• human genetics
• Which Cut Is Older? (It's a Trick Question) New York Times, February 21, 2006 article regarding meat industry use of carbon dioxide 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.