Myeloperoxidase (MPO) belongs to the superfamily of heme peroxidase-cyclooxygenases, and it's mostly found in neutrophils, activated microglia, monocytes/macrophages, astrocytes, and neurons. They are involved in immune surveillance and host defense. Under normal physiological circumstances, MPO counters pathogens through reactive oxygen species chlorides, and inflammacies. However, too much MPO production and activity has been deemed strongly associated with the development and progression of many important diseases. Higher MPO levels in stroke and cardiovascular disease patients are correlated with the severity of the disease and poor outcomes. Hence, modulating MPO activity and its inflammatory activity can bring new concepts and therapeutic approaches for diseases associated with it. Moreover, MPO can also be considered as a biomarker for inflammatory state and development of related pathologies. MPO research will inform us about how it works in diseases and more targeted clinical interventions.
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Myeloperoxidase (MPO) Physiological Activity
Myeloperoxidase (MPO) is mainly a enzyme found in neutrophils and monocytes. It is at the heart of the immune system and also acts as a protector against infection and inflammation. MPO can also lead reactions to generate reactive oxygen species (ROS) including superoxide anions that destroy microbes in local inflammation but damage tissues if too high. During inflammatory reactions, MPO releases promote local blood flow and drive more immune cells to the infected or damaged area. Furthermore, MPO and its constituents also regulate intercellular signaling and the extent of inflammatory reactions.
Structure
The human myeloperoxidase is a cationic dimeric protein containing a single ferrous protoporphyrin IX (heme) per unit. The two heme bands are structurally and functionally identical in MPO. Each heme is bound to the surrounding apoprotein by three covalent bonds, with the result that the heme is a bit curved along the axis from pyrrole ring A to ring C, and the iron ion in the centre is displaced by 0.2 at the close side. These three apoprotein-heme contacts control this heme protein's extraordinary biochemical and redox activity.
Reaction Cycle of Myeloperoxidase
MPO compound I, which results from reacting resting MPO with H2O2, is a very reactive state of ephemeral duration. It reacts easily with (pseudo)halides by sucking up two electrons and oxidising them into hypohalous acids or hypothiocyanates. In this response, sleeping MPO is rebuilt.
Catalytic Mechanism of Myeloperoxidase (MPO)
Myeloperoxidase (MPO) belongs to a significant group of superfamily of heme peroxidase-cyclooxygenase. It can make halide ions (Cl, Br, I ) or pseudohalide ions (SCN) from H2O2 into hypochlorous acid (HClO), hypobromous acid (HBrO), hypoiodous acid (HIO) or hypothiocyanous acid (HSCNO). There are two types of redox reactions the enzyme can perform: halogenation cycle and peroxidase cycle.
Fig. 1 The structure of myeloperoxidase (MPO) (Wang Y., et al. 2013).
Myeloperoxidase (MPO) About Stroke
Myeloperoxidase (MPO) is a prominent inflammatory molecule of the myeloid system found mostly in neutrophils and microglia. Myeloperoxidase and its derivatives can also participate in the initiation and progression of hemorrhagic stroke and ischemic stroke, for example, destruction of the blood-brain barrier and brain. As an unusual inflammatory marker, myeloperoxidase's usefulness is not just assessed by the presence and progression of vascular disease in stroke; more significantly, many basic experiments and clinical trials have established that inhibition or absence of myeloperoxidase affects stroke prognosis.
Myeloperoxidase (Mpo) Is a Highly Efficient Target
Myeloperoxidase (MPO) is an immune and inflammatory enzyme that comes mostly from granulocytes. Modern science has found myeloperoxidase involved in countless illnesses - heart disease, chronic inflammation, stroke. Myeloperoxidase can also be involved in ischemia-reperfusion damage and nerve-cell inflammation in stroke. Myeloperoxidase can oxidise and damage neurons, in studies by producing reaction products such as chloride and peroxide. Moreover, myeloperoxidase is also involved in endothelial dysfunction and thrombosis, so stroke pathology matters too.
Thus therapies that target myeloperoxidase could provide new avenues for stroke prevention and treatment. For instance, stopping myeloperoxidase, or cutting back on its release of poisonous chemicals, with specific inhibitors could ameliorate stroke's impact and improve outcomes. The identification of myeloperoxidase as a new target is far from conclusive, but its role in stroke pathology was already reflected in the data. This makes future research more useful for determining how exactly myeloperoxidase functions in stroke, and if it can be a potential target for treatment.
References
- Wang Y., et al. Research progress of myeloperoxidase inhibitors. Journal of Nanjing Medical University (Natural Science Edition). 2023, 12: 1756-1763.
- Frangie, C., et al. Role of myeloperoxidase in inflammation and atherosclerosis. Biomedical reports. 2022, 16(6): 1-11.
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