Myeloperoxidase is a lysosomal enzyme that is found in white blood cells, neutrophils. Myeloperoxidase is an enzyme that uses hydrogen peroxidase to convert chloride to hypochlorous acid. The produced hypochlorous acid reacts with and destroys bacteria. In many inflammatory pathologies, such as cystic fibrosis and rheumatoid arthritis, neutrophils are also causing tissue damage. Myeloperoxidase is also produced when arteries are inflamed and have rupture-prone fatty deposits. An inflammation in the arteries can lead to a blood clot and eventually to a heart attack or stroke.
Myeloperoxidase is thought to be the most promising cardiac marker at the moment. In addition to that Myeloperoxidase is a good inflammatory biomarker for autoimmune, inflammatory diseases and cancer. Other cardiac markers, like troponin, myoglobin, creatine kinase isoenzyme MB and C-reactive protein, to which tests already exist, become present in the blood only after the damage to the heart has already been done. By measuring the myeloperoxidase level in blood it is possible to predict whether a person is in risk of heart attack or death in the following six months.
Functions of Myeloperoxidase
- Reactions of hypochlorous acid. Oxidative equivalents formed by MPO are involved in numerous processes of tissue damage. Hypochlorous acid is known to oxidize at a significant rate sulfhydryl and thioether groups of proteins [34, 35]. It chlorinates amino groups to chloramines [36, 37]. Because of its strongly cationic properties, MPO is known to be easily attached to negatively charged biological membranes . Thus, reactions with unsaturated bonds of different phospholipids are also quite possible. The formation of chlorohydrins as well as lysophospholipids in unsaturated phosphatidylcholines by hypochlorous acid and by the MPO-H2O2-Cl- system has been recently described [39-41]. MPO products are also involved in initiation of lipid peroxidation. Peroxidation by hypochlorous acid is favored by the presence of hydroperoxides previously accumulated in lipid material [42, 43]. The one-electron oxidation of different substrates by complex I of MPO causes radical products such as tyrosyl radical, which is also known to initiate lipid peroxidation processes [44, 45].
- Attachment of myeloperoxidase to membranes. Plasma levels of free MPO are often elevated in patients during inflammatory conditions [46, 47]. This strongly cationic protein binds to the negatively charged endothelial plasma membrane, whereby this binding depends on the presence of heparin/heparan-containing glycosaminoglycans [48, 49]. Moreover, cell-bound myeloperoxidase rapidly transcytoses the intact endothelium and localizes at the basolateral site of the endothelium closely associated with interstitial matrix proteins such as fibronectin .
- Protein nitration by myeloperoxidase. Nitration of free and protein-bound tyrosine correlates well with myeloperoxidase activity under inflammatory conditions [50, 51]. Compound I of MPO is able to oxidize nitrite to the nitrating species nitrogen dioxide (NO2) at a significant rate . In inflammatory models, the immunoreactivity of MPO strongly co-localizes with the formation of nitrotyrosine in subendothelial and epithelial tissue regions .
- Modulation of the vessel tonus. Myeloperoxidase impairs NO-dependent blood vessel relaxation and guanylate cyclase activation in an inflammatory model by regulating the availability of nitric oxide . This effect is favored by endothelial localization of secreted MPO  and the high rate of NO oxidation by radical products of MPO catalysis [22, 23, 53].
- Termination of PMN responses. Myeloperoxidase also modulates a variety of aspects of the inflammatory response. It is assumed that the MPO-H2O2-halide system inactivates some of the secreted granule contents, decreases the binding of formylated peptides to chemotactic receptors, and influences other functions in stimulated PMNs . Thus, myeloperoxidase contributes to physiological feedback of recruitment of PMNs. It contributes to the termination of the influx of PMNs in inflammatory loci. MPO-deficient PMNs usually exhibit a stronger and more prolonged respiratory burst [55, 56].
- Myeloperoxidase and pathologies. Myeloperoxidase is assumed to be involved in the pathology of different diseases such as atherosclerosis, cancer, multiple sclerosis, and Alzheimer's disease [57-60]. MPO has been found in arteriosclerotic plaques
MPO Defficiency in Candidiasis
The neutrophils and monocytes of most patients with deseminated candidiasis have been found to lack detectable levels of the enzyme myeloperoxidase (MPO). This rarely affects phagocytosis of the organism, but markedly decreases intracellular destruction, resulting in the organism persisting as intracellular inclusion. This perhaps affords an explanation to the persistance of some health care practitioners in employing questionable superoxide therapies in candidiasis. MPO synthesis is dependent on adequate tissue levels of both iodine and ascorbate, the therapeutic employment of which offers a more sound and safe approach.