The myoglobin is a globular protein intracellular found in the cytosol of skeletal and cardiac muscle cells. Its main function is to constitute an oxygen reserve and to promote the intracellular transport of oxygen.
John Kendrew and Max Perutz received the Nobel Prize in Chemistry in 1962 for their studies on globular proteins. These authors elucidated the three-dimensional structure of myoglobin and hemoglobin, respectively. Historically, myoglobin was one of the first proteins from which the three-dimensional structure was determined.
Graphic representation of the molecular structure of three oxygenated proteins: leghemoglobin, hemoglobin, and myoglobin (Source: Veronica Stafford / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0) via Wikimedia Commons)
Globular proteins are compact molecules with a spherical shape; they are soluble in the cytosol or in the lipid portion of cell membranes. They are responsible for the main biological actions, in contrast to fibrous proteins, whose main functions are structural.
Myoglobin gives fresh meat its red color. This occurs when myoglobin is oxygenated as oxymyoglobin and the iron that composes it is in the form of ferrous iron: Mb-Fe2 + O2.
When the meat is exposed to the environment, unstable ferrous iron oxidizes and becomes ferric and under these conditions the color changes to brown tones due to the formation of methamyoglobin (Mb-Fe3 + + O2-).
Normally blood myoglobin levels are very small, they are in the order of micrograms per liter (μg / L). These levels increase when muscle destruction occurs as in skeletal muscle rhabdomyolysis or in cardiac infarction with tissue destruction and in some myopathies.
Its presence in the urine is observed in certain conditions in which tissue damage is very important. Its early diagnostic value for heart attack is debatable.
Structure of myoglobin
Myoglobin has a molecular weight of almost 18 kDa including the heme group. It is made up of four helical segments joined by "sharp turns". These myoglobin helices are tightly packed and maintain their structural integrity even when the heme group is removed.
The structure of globular proteins, as well as of all cellular proteins, is hierarchical so the structure of myoglobin is also hierarchical. The first level is the primary structure formed by the linear sequence of amino acids and myoglobin is constituted by a chain of 153 amino acids.
Graphic scheme of the helical and globular structure of myoglobin (Source: Dcrjsr / CC BY (https://creativecommons.org/licenses/by/3.0) via Wikimedia Commons)
The secondary structure of myoglobin consists of the conformation of the alpha helices. Myoglobin contains 8 alpha helices formed by repeating polypeptide portions that are joined by short segments of aperiodic arrangement.
The tertiary structure consists of the three-dimensional conformation with biological activity. The most important characteristics of this structure are the folds. The quaternary structure refers to the assembly of two or more polypeptide chains separated and linked through non-covalent bonds or interactions.
Myoglobin and its heme prosthetic group (Source: Thomas Splettstoesser / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0) via Wikimedia Commons)
Myoglobin has a very compact structure, with hydrophobic residues directed inward and hydrophilic or polar residues directed outward. The internal apolar residues are made up of leucine, valine, methionine, and phenylalanine. The only internal polar residues are two histidines that have functions at the active site.
The prosthetic heme group is located in a cleft in the apolar inner part of the polypeptide chain of myoglobin. This group contains iron in the form of ferrous iron, which binds with oxygen to form oxymyoglobin.
Function
The function of myoglobin is to bind oxygen to the heme group of its structure and to form an oxygen reserve for muscle function. As oxygen is trapped in the myoglobin structure in the cytoplasm of the muscle cell, its intracellular pressure, determined by free oxygen, remains low.
Low intracellular oxygen pressure maintains the gradient for oxygen entry into the cell. This favors the passage of oxygen from the bloodstream to the muscle cell. When myoglobin is saturated, intracellular oxygen increases, which progressively decreases the gradient and thus decreases the transfer.
The binding curve of oxygen to myoglobin is hyperbolic. In the initial portions of the curve small changes in the partial pressure of oxygen produce large changes in the saturation of myoglobin with oxygen.
Then, as the partial pressure of oxygen increases, the saturation continues to increase, but more slowly, that is, a much greater increase in the partial pressure of oxygen is needed to increase the saturation of myoglobin, and progressively the curve flattens out.
There is a variable that measures the affinity of the curve called P50, this represents the partial pressure of oxygen necessary to saturate the myoglobin contained in a solution by 50%. Thus, if the P50 increases, it is said that myoglobin has a lower affinity and if the P50 decreases, it is said that myoglobin has a higher affinity for oxygen.
When the oxygen binding curves for myoglobin and hemoglobin are examined, it is observed that for any partial pressure of oxygen examined, myoglobin is more saturated than hemoglobin, indicating that myoglobin has a higher affinity for oxygen than hemoglobin.
Types of muscle fibers and myoglobin
Skeletal muscles have different types of muscle fibers in their composition, some called slow twitch and others fast twitch. Fast twitch fibers are structurally and metabolically adapted to contract rapidly and vigorously and anaerobically.
Slow-twitch fibers are adapted for slow-speed, but longer, contractions typical of resistance aerobic exercise. One of the structural differences of these fibers is the concentration of myoglobin, which gives them the name of white and red fibers.
Red fibers have a high content of myoglobin, which gives them the red color, but which also allows them to maintain large amounts of oxygen, which is essential for their function.
Normal values
Normal blood values for men are 19 to 92 µg / l and for women 12 to 76 µg / l, however, there are differences in the values in different laboratories.
These values increase when muscle destruction occurs, as occurs in skeletal muscle rhabdomyolysis, in extensive burns, electrical shocks or in extensive muscle necrosis due to arterial occlusion, in myocardial infarction and in some myopathies.
Under these conditions myoglobin appears in urine and gives it a characteristic color.
References
- Fauci, AS, Kasper, DL, Hauser, SL, Jameson, JL, & Loscalzo, J. (2012). Harrison's principles of internal medicine. DL Longo (Ed.). New York: Mcgraw-hill
- Ganong WF: Central Regulation of Visceral Function, in Review of Medical Physiology, 25th ed. New York, McGraw-Hill Education, 2016.
- Guyton AC, Hall JE: The Body Fluid Compartments: Extracellular and intracellular fluids; Edema, in Textbook of Medical Physiology, 13th ed, AC Guyton, JE Hall (eds). Philadelphia, Elsevier Inc., 2016.
- McCance, KL, & Huether, SE (2018). Pathophysiology-Ebook: the biologic basis for disease in adults and children. Elsevier Health Sciences.
- Murray, RK, Granner, DK, Mayes, PA, & Rodwell, VW (2014). Harper's illustrated biochemistry. Mcgraw-hill.