Structural Biochemistry/Protein function/Heme group/Myoglobin
History[edit | edit source]
Myoglobin was the first protein whose structure was determined. In 1958, Max Perutz and John Kendrew determined the 3D structure of myoglobin by X-ray crystallography. Four years later, they both received the Nobel Prize in chemistry for this innovation.
Structure[edit | edit source]
Myoglobin is a monomeric protein that has 154 amino acids residues. It consists of eight α-helicines connected through the turns with an Oxygen binding site. It has a globular structure. Myoglobin contains a heme (prosthetic) group which is responsible for its main function (carrying of oxygen molecules to muscle tissues). Myoglobin can exist in the oxygen free form, deoxymyoglobin, or in a form in which the oxygen molecule is bound, called oxymyoglobin. Myoglobin is a protein found in muscles that binds oxygen with its heme group like hemoglobin. Heme group consists of protoporphyrin organic component and an iron atom located in its center. The heme group gives muscle and blood their distinctive red color. The organic component consists of four pyrrole rings that are linked by methine bridges. In addition, heme is responsible for the red color of the blood and muscle. Oxidation of the iron atom (Fe2+ -> Fe3+) is mainly responsible for the color of muscle and blood. At the center of protoporphyrin, the iron atom is bonded to nitrogen atoms from four pyrrole rings. The iron atom can form two additional bonds, one on each side of the heme plane. These binding sites are called the fifth and sixth coordination sites. In myoglobin, the fifth coordination site is occupied by the imidazole ring from a histidine residue on the protein. This histidine is referred to as the proximal histidine. The sixth coordination site is available to bind oxygen. The iron atom in deoxymyoglobin lies about four angstroms out of the plane of the protoporphyrin plane because it is too big in that form to fit into the well defined hole.
The normal oxidation state of an iron atom has a positive two charge (ferrous ion) instead of three charge (ferric ion) and it is too large to fit into the plane of protoporphyrin. Thus, a ferrous ion is often 0.4 Å away from the porphyrin plane. However, when iron oxidized from ferrous ion (Fe2+) to ferric ion (Fe3+), because the loss of one extra electron, forces between protons and electrons increases so that the electron cloud will penetrate more towards to the nucleus. As a result, the ferric ion (Fe3+) has a smaller size then ferrous ion (Fe2+) and fits into the protoporphyrin plane when it attaches to an oxygen.
When oxygen leaves the myoglobin, it leaves as dioxygen rather than superoxide. This is because superoxide can be damaging to many biological process, and in the leaving of superdioxide, the iron ion will be in the ferric state which stops biding oxygen.
The distal histidine amino acid from the hemoglobin protein molecule further stabilizes the O2 molecule by hydrogen-bonding interactions.
Myoglobin is a protein molecule that has a similar structure and function to hemoglobin. It is a smaller monomer of polypeptide structure, a globular protein with amino acids and prosthetic heme group binds to proximal histidine group while a distal histidine group interact on the other side of the plane. It binds and stores oxygen without concerning cooperativity. Most importantly, it is the first protein structure to be studied.
Myoglobin follows the Michaelis-Menten Kinetic graph (as seen from the graph above). It follows the Michaelis-Menten kinetics because it is a simple chemical equilibrium.
Function[edit | edit source]
The binding affinities for oxygen between myoglobin and hemoglobin are important factors for their function. Both myoglobin and hemoglobin binds oxygen well when the concentration of oxygen is really high (E.g. in Lung), however, hemoglobin is more likely to release oxygen in areas of low concentration (E.g. in tissues). Since hemoglobin binds oxygen less tightly than myoglobin in muscle tissues, it can effectively transport oxygen throughout the body and deliver it to the cells. Myoglobin, on the other hand, would not be as efficient in transferring oxygen. It does not show the cooperative binding of oxygen because it would take up oxygen and only release in extreme conditions. Myoglobin has a strong affinity for oxygen that allows it to store oxygen in muscle effectively. This is important when the body is starved for oxygen, such as during anaerobic exercise. During that time, carbon dioxide level in blood streams is extremely high and lactic acid concentration build up in muscles. Both of these factors cause myoglobin (and hemoglobins) to release oxygen, for protecting the body tissues from getting damaged under harsh conditions. If the concentration of myoglobin is high within the muscle cells, the organism is able to utilize the oxygen in its lungs for a much longer period of time.
Myoglobin, an iron-containing protein in muscle, receives oxygen from the red blood cells and transports it to the mitochondria of muscle cells, where the oxygen is used in cellular respiration to produce energy. Each myoglobin molecule has one heme prosthetic group located in the hydrophobic cleft in the protein. The function of myoglobin is notable from Millikan's review (1) in which he put together an accomplished study to establish that myoglobin is formed adaptively in tissues in response to oxygen needs and that myoglobin contributes to the oxygen supply of these tissues. Oxymyoglobin regulates both oxygen supply and utilization by acting as a scavenger of the bioactive molecule nitric oxide. Nitric oxide is generated continuously in the myocyte. Oxymyoglobin reacts with NO to form harmless nitrates, with concomitant formation of ferric myoglobin, which is recycled through the action of the intracellular enzyme metmyoglobin reductase. Flogel (2) conducted a study that showed how the interaction of NO and oxymyoglobin controls cardiac oxygen utilization.
Disease[edit | edit source]
When muscle tissue is damaged, very large concentrations of myoglobin enters the kidneys. When this happens, myoglobin is then considered highly toxic and may contribute to acute renal failure. Muscle injury is commonly associated with the release of myoglobin, and is known to be the cause of heart attacks and many other myoalgia. Studies have shown that acute myocardial infarction can be detected with the help of the monitoring of creatin kinase and troponin by electrocardiogram.
References[edit | edit source]
(1) Millikan, G. A. (1939). Muscle hemoglobin. Physiol. Rev. 19,503 -523.
(2) Flogel, U., Merx, M. W., Godecke, A., Decking, U. K. M. and Schrader, J. (2001). Myoglobin: a scavenger of bioactive NO. Proc. Natl. Acad. Sci. USA 98,735 -740