Myoglobin

Myoglobin is a cytoplasmic hemoprotein composed by a single polypeptide chain of 154 amino acids. It is expressed solely in cardiac myocytes and oxidative skeletal muscle fibers. Myoglobin was so named because of its functional and structural similarity to hemoglobin. Like hemoglobin, myoglobin binds reversibly to O2 and thus may facilitate the transport of O2 from red blood cells to the mitochondria during periods of increased metabolic activity or serve as an O 2 reservoir during hypoxia or anoxia.The structure of myoglobin was first delineated by John Kendrew more than 40 years ago and subsequent work has shown that it is a polypeptide chain consisting of eight α-helices. It binds oxygen to its heme residue, a porphyrin ring with an iron ion. The polypeptide chain is folded and packs the heme prosthetic group, positioning it between two histidine, His64 and His93 residues. The iron ion interacts with six ligands, four of which are supplied by the nitrogen atoms of the four pyrrhols and share a common plane. The side chain imidazole of His93, provides the fifth ligand, stabilizing the heme group and slightly displacing the iron ion out of the heme plane. The position of the sixth ligand, in deoximoglobin, serves as the binding site for O2, as well as for other potential ligands, such as CO or NO. When O2 binds, the iron ion, it is partially drawn back toward the porphyrin plane. Although this shift is of little importance in the function of monomeric myoglobin, it provides the basis for the conformational changes that underlie the allosteric properties of tetrameric hemoglobin. In addition, studies using X-ray diffraction and xenon binding techniques have identified four highly conserved internal cavities within the myoglobin molecule that can help target molecules to bind to the heme residue.Related to its role as an O2 reservoir, myoglobin also functions as an intracellular pO2 buffer (partial pressure of O2). Similarly to the role of creatine phosphokinase, which works to buffer ATP concentrations when muscle activity increases, myoglobin works to buffer O2 concentrations. As a result, the intracellular concentration of O2 remains relatively constant and homogeneous, despite increases in O2 flow from the capillaries to the mitochondria, induced by physical activity.

Text written by:

Ana Rita Cardoso

João Faria

Joel Mateus

Pedro Desport
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Cartoon about Cell-fies

Oxidative stress and cellular respiration

During cellular respiration, electrons are transferred from NADH or FADH2, along 4 protein complexes in the inner mitochondrial membrane, to an O₂ molecule (read more about this subject here). In the last stage of the process, the electrons are transported one by one, that is, they will reach the oxygen one at a time. 

This situation, which may seem only a detail to many, has, in fact, very important implications for our biochemistry, because it means that all O₂ molecules are, even temporarily, transformed into a free radical, the superoxide anion. This means that, literally, at every instant we are producing large quantities of reactive oxygen species. However, this situation, which is potentially very dangerous, does not have, under normal conditions, dramatic consequences for cells, mainly for 2 reasons:
1. There are mechanisms that prevent the superoxide anion from diffusing from complex 4 before it is completely reduced to water. That is, the free radical is formed, but remains in place and quickly receives another electron, ceasing to be free radical.
2. As there are always some superoxide anions that can escape the first mechanism, we have other defense mechanisms, and in this context, the most important is the presence of a mitochondrial enzyme called superoxide dismutase. This enzyme, which also has a cytosolic isoform, will cause dismutation of the superoxide anion, converting two of these molecules into hydrogen peroxide.
Of course there will also be superoxide anions that will be able to escape from superoxide dismutase, but under normal conditions these are very few. In addition, we still have several other antioxidant defenses waiting for them...

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Metabolic map about the surface proteins of cytotoxic T cells