Myeloperoxidase

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Myeloperoxidase
Myeloperoxidase.png
Myeloperoxidase drawn from PDB 1D7W.
Identifiers
Symbol(s) MPO;
External IDs OMIM: 606989 MGI97137 Homologene55450
RNA expression pattern

PBB GE MPO 203948 s at tn.png

PBB GE MPO 203949 at tn.png

More reference expression data

Orthologs
Human Mouse
Entrez 4353 17523
Ensembl ENSG00000005381 ENSMUSG00000009350
Uniprot P05164 Q571G0
Refseq NM_000250 (mRNA)
NP_000241 (protein)
NM_010824 (mRNA)
NP_034954 (protein)
Location Chr 17: 53.7 - 53.71 Mb Chr 11: 87.61 - 87.62 Mb
Pubmed search [1] [2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]

Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [4] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.

Overview

Myeloperoxidase (MPO) is a peroxidase enzyme (EC 1.11.1.7) most abundantly present in neutrophil granulocytes (a subtype of white blood cells). It is a lysosomal protein stored in azurophilic granules of the neutrophil. MPO has a heme pigment, which causes its green color in secretions rich in neutrophils, such as pus and some forms of mucus.

Studies have demonstrated neutrophil activation as they pass through the coronary bed in patients with ACS.[1] Furthermore, MPO levels have recently been shown to be an independent predictor of outcome in ACS.[2] [3]

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 heme group. Three isoforms have been identified, differing only in the size of the heavy chains[4]. It contains a calcium binding site with 7 ligands forming a pentagonal pyramid conformation. One of the ligands is the 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 hypochlorous acid (HOCl) from hydrogen peroxide (H2O2) and chloride anion (Cl-) during the neutrophil's respiratory burst. It requires heme as a cofactor. Furthermore, it oxidizes tyrosine to tyrosyl radical using hydrogen peroxide as oxidizing agent.[5]

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

Genetics

The gene is located on chromosome 17 (17q23.1).

Role in disease

Myeloperoxidase deficiency is a hereditary deficiency of the enzyme, which predisposes to immune deficiency.[6]

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

Diagnostic use

Routine testing of MPO is not performed. A 2003 study suggested that it could serve as a sensitive predictor for myocardial infarction in patients presenting with chest pain.[7] Currently, PrognostiX Inc., run out of the Cleveland Clinic in Cleveland, Ohio, is the only company to have an FDA approved ELISA test kit for MPO concentration. The product is known as CardioMPO and is used in clinical settings to triage patients that present chest pain. It operates using the sandwich ELISA method.

Historically, immunohistochemical staining for myeloperoxidase was used in the diagnosis of acute myeloid leukemia to demonstrate that the leukemic cells were derived from the myeloid lineage. However, more recently, the use of myeloperoxidase staining in this setting has been supplanted by the widespread use of flow cytometry. Myeloperoxidase staining is still important in the diagnosis of extramedullary leukemia, or chloroma.

See also

References

  1. PMID 12097534
  2. PMID 12952835
  3. PMID 14573731
  4. M Mathy-Hartert; et al. (1998). "Purification of myeloperoxidase from equine polymorphonuclear leucocytes". Can J Vet Res. 62 (2): 127-132. 
  5. Heinecke JW, Li W, Francis GA, Goldstein JA. Tyrosyl radical generated by myeloperoxidase catalyzes the oxidative cross-linking of proteins. J Clin Invest 1993;91:2866-72. PMID 8390491.
  6. Kutter D, Devaquet P, Vanderstocken G, Paulus JM, Marchal V, Gothot A. Consequences of total and subtotal myeloperoxidase deficiency: risk or benefit? Acta Haematol 2000;104:10-5. PMID 11111115.
  7. Brennan M-L, Penn MS, Van Lente F, Nambi V, Shishehbor MH, Aviles RJ, Goormastic M, Pepoy ML, McErlean ES, Topol EJ, Nissen SE, Hazen SL. Prognostic value of myeloperoxidase in patients with chest pain. N Engl J Med 2003;349:1595-604. PMID 14573731.


Cost Effectiveness of Myeloperoxidase

| group5 = Clinical Trials Involving Myeloperoxidase | list5 = Ongoing Trials on Myeloperoxidase at Clinical Trials.govTrial results on MyeloperoxidaseClinical Trials on Myeloperoxidase at Google


| group6 = Guidelines / Policies / Government Resources (FDA/CDC) Regarding Myeloperoxidase | list6 = US National Guidelines Clearinghouse on MyeloperoxidaseNICE Guidance on MyeloperoxidaseNHS PRODIGY GuidanceFDA on MyeloperoxidaseCDC on Myeloperoxidase


| group7 = Textbook Information on Myeloperoxidase | list7 = Books and Textbook Information on Myeloperoxidase


| group8 = Pharmacology Resources on Myeloperoxidase | list8 = AND (Dose)}} Dosing of MyeloperoxidaseAND (drug interactions)}} Drug interactions with MyeloperoxidaseAND (side effects)}} Side effects of MyeloperoxidaseAND (Allergy)}} Allergic reactions to MyeloperoxidaseAND (overdose)}} Overdose information on MyeloperoxidaseAND (carcinogenicity)}} Carcinogenicity information on MyeloperoxidaseAND (pregnancy)}} Myeloperoxidase in pregnancyAND (pharmacokinetics)}} Pharmacokinetics of Myeloperoxidase


| group9 = Genetics, Pharmacogenomics, and Proteinomics of Myeloperoxidase | list9 = AND (pharmacogenomics)}} Genetics of MyeloperoxidaseAND (pharmacogenomics)}} Pharmacogenomics of MyeloperoxidaseAND (proteomics)}} Proteomics of Myeloperoxidase


| group10 = Newstories on Myeloperoxidase | list10 = Myeloperoxidase in the newsBe alerted to news on MyeloperoxidaseNews trends on Myeloperoxidase</small>


| group11 = Commentary on Myeloperoxidase | list11 = Blogs on Myeloperoxidase

| group12 = Patient Resources on Myeloperoxidase | list12 = Patient resources on MyeloperoxidaseDiscussion groups on MyeloperoxidasePatient Handouts on MyeloperoxidaseDirections to Hospitals Treating MyeloperoxidaseRisk calculators and risk factors for Myeloperoxidase


| group13 = Healthcare Provider Resources on Myeloperoxidase | list13 = Symptoms of MyeloperoxidaseCauses & Risk Factors for MyeloperoxidaseDiagnostic studies for MyeloperoxidaseTreatment of Myeloperoxidase

| group14 = Continuing Medical Education (CME) Programs on Myeloperoxidase | list14 = CME Programs on Myeloperoxidase

| group15 = International Resources on Myeloperoxidase | list15 = Myeloperoxidase en EspanolMyeloperoxidase en Francais

| group16 = Business Resources on Myeloperoxidase | list16 = Myeloperoxidase in the MarketplacePatents on Myeloperoxidase

| group17 = Informatics Resources on Myeloperoxidase | list17 = List of terms related to Myeloperoxidase


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