Sandbox WWC11: Difference between revisions
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'''Structure''' | '''Structure''' | ||
Myeloperoxidase is synthesized in bone marrow along with most other white blood cell components. The myloperoxidase enzyme is composed of two identical subunits. After translation of these subunits, they are cleaved into two parts: the heavy chain and the light chain. The heavy chain is a glycosylated domain that weighs approximately 58.5kDa. This portion of the enzyme has the deep pocket where the heme is inserted into by chaperones(calreticulin and calnexin). 26904693 The amino acid make up of heme pocket can be seen in Figure 1. The pink in this picture is the light chain, the blue is the heavy chain. The light chain (about 13.5kDa) is attached to the heavy chain through disufide bonds. There have been discoveries of slight variation in the primary sequence of myeloperoxidase. However, for the most part these slight variations do not affect the enzymatic activity. Currently three isoforms have been isolated. 120019 | Myeloperoxidase is synthesized in bone marrow along with most other white blood cell components. The myloperoxidase enzyme is composed of two identical subunits. After translation of these subunits, they are cleaved into two parts: the heavy chain and the light chain. The heavy chain is a glycosylated domain that weighs approximately 58.5kDa. This portion of the enzyme has the deep pocket where the heme is inserted into by chaperones(calreticulin and calnexin). <ref name="Neutrophil">PMID:26904693</ref> | ||
The amino acid make up of heme pocket can be seen in Figure 1. The pink in this picture is the light chain, the blue is the heavy chain. The light chain (about 13.5kDa) is attached to the heavy chain through disufide bonds. There have been discoveries of slight variation in the primary sequence of myeloperoxidase. However, for the most part these slight variations do not affect the enzymatic activity. Currently three isoforms have been isolated. <ref name="Enzymatic Activity">PMID:120019</ref> | |||
[[Image: | [[Image:Example.jpg]] | ||
Figure 1. Depicts key amino acids in stabilization of heme in myeloperoxidase. <ref name="Myeloperoxidase">PMID:26884610</ref> | |||
'''Function''' | '''Function''' | ||
[[Image:Example.jpg]] | |||
Figure 2. The Enzymatic Activity of Myeloperoxidase. 21297906 | |||
As stated before, the role of the myeloperoxidase in the immune response is to generate oxidative molecules that are used to damage invaders. Seen above in Figure 1 is a concise and basic diagram of the process. Compounds I, II and III are the different oxidation states of the iron in the heme molecule. One of the processes facilitated by myeloperoxidase is to oxidize hydrogen peroxide (H2O2) and cause the iron to change oxidation states. In this state, the iron is then able to catalyze the production of the hypohalous acids. These molecules are able to reek havoc on lipids, proteins and DNA. <ref name="Neutrophil">PMID:26904693</ref> These modifications are achieve by the oxidation (usually the addition of the halogen) of the unlucky recipient. The heme iron can also be oxidized by radicals to form compounds II and III. The functions of these are less well known, but the productions of these radicals is also helpful in the antibacterial response.<ref name="Myeloperoxidase">PMID:26884610</ref> | |||
Now that the enzymatic properties of myeloperoxidase has been explore, it is time to turn to the bigger picture. These enzymes are stored in the subtype of leukocytes(white blood cells) called neutrophils. These are thought to be one of the first cells types at the site of infection.<ref name="Neutrophil">PMID:26904693</ref> An outline of the immune response of neutrophil, specifically highlighting MPO's role, can be seen in Figure 3 below. There are two paths seen in this figure. In the first the bacteria gets taken up by neutrophil extracellular traps or NETs and then destroyed by the hypohalogous acids. The second path shows the MPO being released, signaled by the dendrite cells(DCs), and helping to destroy the pathogen.<ref name="Neutrophil">PMID:26904693</ref> ANCA stands for anti-neutrophil cytoplasmic antibody. The myeloperoxidase have a range of function that are steered by the neutophil cells. This intense oxidative power is very helpful when targeted to foreign bodies. However, as discussed in the next section, it can very destructive if release on our own tissue. | |||
[[Image:Example.jpg]] | |||
Figure 3. The immune response of neutrophils with specific emphasis on myeloperoxidase.<ref name="Neutrophil">PMID:26904693</ref> | |||
'''Implication of Potential Defects or Deficiencies''' | '''Implication of Potential Defects or Deficiencies''' | ||