Myeloperoxidase

Myeloperoxidase (MPO) is a is_associated_with::peroxidase is_associated_with::enzyme that in humans is encoded by the MPO is_associated_with::gene. Myeloperoxidase is most abundantly expressed in is_associated_with::neutrophil granulocytes (a subtype of is_associated_with::white blood cells). It is a lysosomal protein stored in is_associated_with::azurophilic granules of the neutrophil and released into the extracellular space during degranulation. MPO has a is_associated_with::heme pigment, which causes its green color in secretions rich in neutrophils, such as is_associated_with::pus and some forms of is_associated_with::mucus.

Structure
The 150-kDa MPO protein is a dimer consisting of two 15-kDa light chains and two variable-weight glycosylated heavy chains bound to a prosthetic is_associated_with::heme group. Three is_associated_with::isoforms have been identified, differing only in the size of the heavy chains. It contains a calcium binding site with seven is_associated_with::ligands, forming a pentagonal pyramid conformation. One of the ligands is the is_associated_with::carbonyl group of Asp 96. Calcium-binding is important for structure of the active site because of Asp 96's close proximity to the catalytic His95 side chain.

Function
MPO produces is_associated_with::hypochlorous acid (HOCl) from is_associated_with::hydrogen peroxide (H2O2) and is_associated_with::chloride is_associated_with::anion (Cl−) (or the equivalent from a non-chlorine halide) during the neutrophil's is_associated_with::respiratory burst. It requires heme as a cofactor. Furthermore, it oxidizes is_associated_with::tyrosine to tyrosyl radical using is_associated_with::hydrogen peroxide as an is_associated_with::oxidizing agent.

is_associated_with::Hypochlorous acid and tyrosyl radical are is_associated_with::cytotoxic, so they are used by the neutrophil to kill is_associated_with::bacteria and other is_associated_with::pathogens.

Inhibitors of MPO
is_associated_with::Azide has been used traditionally as an MPO inhibitor, but 4-aminobenzoic acid hydrazide (4-ABH) is a more specific inhibitor of MPO.

Genetics
The human is_associated_with::gene is located on is_associated_with::chromosome 17 (17q23.1).

Role in disease
is_associated_with::Myeloperoxidase deficiency is a hereditary deficiency of the enzyme, which predisposes to is_associated_with::immune deficiency.

Antibodies against MPO have been implicated in various types of is_associated_with::vasculitis, most prominently crescentic is_associated_with::glomerulonephritis and is_associated_with::Churg-Strauss syndrome. They are detected as perinuclear ANCAs (is_associated_with::p-ANCAs), as opposed to the cytoplasmic ANCAs (is_associated_with::c-ANCAs) against proteinase-3 (PR3), which are strongly associated with is_associated_with::granulomatosis with polyangiitis.

Recent studies have reported an association between elevated myeloperoxidase levels and the severity of is_associated_with::coronary artery disease. And Heslop et al. reported that elevated MPO levels more than doubled the risk for cardiovascular mortality over a 13-year period. It has also been suggested that myeloperoxidase plays a significant role in the development of the atherosclerotic lesion and rendering plaques unstable.

Medical uses
An initial 2003 study suggested that MPO could serve as a sensitive predictor for is_associated_with::myocardial infarction in patients presenting with is_associated_with::chest pain. Since then, there have been over 100 published studies documenting the utility of MPO testing. The 2010 Heslop et al. study reported that measuring both MPO and CRP (C-reactive protein; a general and cardiac-related marker of inflammation) provided added benefit for risk prediction than just measuring CRP alone.

Immunohistochemical staining for myeloperoxidase used to be administered in the diagnosis of is_associated_with::acute myeloid leukemia to demonstrate that the leukemic cells were derived from the is_associated_with::myeloid lineage. However, the use of myeloperoxidase staining in this setting has been supplanted by the widespread use of is_associated_with::flow cytometry. Myeloperoxidase staining is still important in the diagnosis of is_associated_with::myeloid sarcoma, contrasting with the negative staining of is_associated_with::lymphomas, which can otherwise have a similar appearance.

Myeloperoxidase is the first and so far only human enzyme known to break down is_associated_with::carbon nanotubes, allaying a concern among clinicians that using nanotubes for targeted delivery of medicines would lead to an unhealthy buildup of nanotubes in tissues.