Myeloperoxidase

Myeloperoxidase (MPO ) is an enzyme in neutrophils of chordates, which plays an important role in the regulation and termination of inflammatory processes. The enzyme catalyzes the oxidation of chloride ions by means of hydrogen peroxide:

The hypochlorite ions formed oxidize various biomolecules and thus contribute to the recognition and uptake by phagocytes with apoptotic material.

  • 5.1 MPO deficiency
  • 5.2 antibodies against MPO
  • 5.3 Myeloperoxidase as a biomarker of joint disease in the horse

Occurrence

Myeloperoxidase expressed in neutrophils, monocytes, tissue macrophages, such as various cells and Kupffer cells, microglia, as well as in AD patients and in nerve cells. In neutrophils and monocytes MPO can make 1-5% of the total cell protein content and is stored in azurophilic granules in leukocytes. After phagocyte MPO is secreted in phagolysosomal compartments and in the extracellular space. The absorption properties of the MPO contribute significantly to the greenish- yellow color of the pus.

Properties

Myeloperoxidase is a 150 - kDa protein consisting of two small (15 kDa each ) and two large subunits, of which at least three isoforms of 57, 59 or 60 kDa size exist. MPO is rich in arginine and thus basic. With an IP Rating of > 10 MPO is strongly cationic at neutral pH. MPO belongs to a group of peroxidases, which a covalently bonded, curved hem is common. Wherein MPO is derived from heme B M heme, which is also referred to as a green heme due to its absorption properties. The methylene carbon atom of the heme C ring is esterified with Asp94 of the protein, the methylene carbon atom of the heme A ring is esterified with the carboxylate oxygen atom of Glu242. The terminal carbon atom of the vinyl group of the A- ring is bonded to the sulfur atom of ional Met243. Along an imaginary axis through the A- and C-ring of the heme heme M MPO is bent by 14 °.

Functions

Catalytic Activity

During the oxidative burst of neutrophils MPO forms hydrogen peroxide (H2O2 ), and chloride and bromide anions (Cl -, Br - ), chlorine (Cl2), bromine ( Br2 ), and bromine chloride ( BrCl ). Under physiological conditions, incurring immediately hypochlorite ( HClO ) and hypobromite ( HBrO ). Besides halides MPO shape I also oxidizes nitrite ( NO2), nitric oxide (NO), thiocyanate ( SCN- ) and tyrosine.

Effect on biomolecules

Reactive HClO reacts with a plurality of oxidizable biomolecules that contain unsaturated double bonds, thiols and various nitrogen compounds. The chlorination takes place substantially with pyridine nucleotides (e.g., NAD ), cholesterol and unsaturated fatty acids with the formation of chlorohydrins, and amino groups under formation of chloramines. In effect causes MPO activity that is oxidized, for example high cholesterol LDL, membrane lipids are oxidized and Tyr residues of proteins are made ​​reactive, all processes that have at least regulatory function.

Role in inflammation

Myeloperoxidase binds electrostatic reasons to phosphatidylserine and therefore specific to the outer membrane of apoptotic cells.

Role in infections

Unlike previously thought appears to have no general antimicrobial activity of MPO. Although a part of the displayed formed by the MPO halogenated products in the chemical control of infectious particles plausible but show MPO knockout mice and human with MPO Defiziens no increased susceptibility to bacterial infections. Only infection with the fungus Candida albicans occurred in these individuals to frequently.

Genetics

The human MPO gene is located on chromosome 17, locus 17q23.1.

Diseases

MPO deficiency

There are currently no evidence-based data about the fact that patients with MPO deficiency show increased susceptibility to Candida albicans infections and a generally increased risk of inflammation. Most publications could not detect any increase in the incidence of infections in the majority of patients.

Antibodies against MPO

If it comes to the formation of autoantibodies against MPO, enter these antibodies perinuclear antineutrophil cytoplasmic antibodies as so-called Pancas in appearance. These play a role in various vasculitides such as Churg -Strauss syndrome and rapidly progressive glomerulonephritis.

Myeloperoxidase as a biomarker of joint disease in the horse

The myeloperoxidase activity is elevated in the synovial fluid of joints with septic arthritis in the horse compared to healthy joints and joints with non- septic diseases.

Protein isoform Human Genome Organisation Respiratory burst LDL (disambiguation) Anti-neutrophil cytoplasmic antibody Vasculitis Digital Object Identifier
589148
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