Myeloperoxidase


Myeloperoxidase
Myeloperoxidase

Myeloperoxidase drawn from PDB 1D7W.
Identifiers
Symbols MPO;
External IDs OMIM606989 MGI97137 HomoloGene55450 GeneCards: MPO Gene
EC number 1.11.2.2
RNA expression pattern
PBB GE MPO 203948 s at tn.png
PBB GE MPO 203949 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4353 17523
Ensembl ENSG00000005381 ENSMUSG00000009350
UniProt P05164 Q571G0
RefSeq (mRNA) NM_000250.1 NM_010824.2
RefSeq (protein) NP_000241.1 NP_034954.2
Location (UCSC) Chr 17:
56.35 – 56.36 Mb
Chr 11:
87.61 – 87.62 Mb
PubMed search [1] [2]

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.

Contents

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.[1] It contains a calcium binding site with seven 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-) (or the equivalent from a non-chlorine halide) during the neutrophil's respiratory burst. It requires heme as a cofactor. Furthermore, it oxidizes tyrosine to tyrosyl radical using hydrogen peroxide as an oxidizing agent.[2]

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

Inhibitors of MPO

Azide has been used traditionally as an MPO inhibitor, but 4-aminobenzoic acid hydrazide (4-ABH) is a more specific inhibitor of MPO.[3]

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.[4]

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.

Recent studies have reported an association between myeloperoxidase levels and the severity of coronary artery disease.[5] It has been suggested that myeloperoxidase plays a significant role in the development of the atherosclerotic lesion and rendering plaques unstable.[6][7]

Medical uses

An initial 2003 study suggested that MPO could serve as a sensitive predictor for myocardial infarction in patients presenting with chest pain.[8] Since then, there have been over 100 published studies documenting the utility of MPO testing. Most recently, Heslop et al. reported that elevated MPO levels more than doubled the risk for cardiovascular mortality over a 13-year period, and 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.[9]

Immunohistochemical staining for myeloperoxidase used to be administered in the diagnosis of acute myeloid leukemia to demonstrate that the leukemic cells were derived from the myeloid lineage. However, 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.

Myeloperoxidase is the first and so far only human enzyme known to break down 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.[10]

See also

  • Chloroma

References

  1. ^ M Mathy-Hartert et al. (1998). "Purification of myeloperoxidase from equine polymorphonuclear leucocytes". Can J Vet Res. 62 (2): 127–132. PMC 1189459. PMID 9553712. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1189459. 
  2. ^ 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.
  3. ^ Kettle AJ, Gedye CA, Winterbourn CC (January 1997). "Mechanism of inactivation of myeloperoxidase by 4-aminobenzoic acid hydrazide". Biochem. J.. 321 ( Pt 2): 503–8. PMC 1218097. PMID 9020887. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1218097. 
  4. ^ 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.
  5. ^ Zhang R, Brennan ML, Fu X, et al. (November 2001). "Association between myeloperoxidase levels and risk of coronary artery disease". JAMA 286 (17): 2136–42. doi:10.1001/jama.286.17.2136. PMID 11694155. http://jama.ama-assn.org/content/286/17/2136.long. 
  6. ^ Nicholls SJ, Hazen SL (June 2005). "Myeloperoxidase and cardiovascular disease". Arterioscler. Thromb. Vasc. Biol. 25 (6): 1102–11. doi:10.1161/01.ATV.0000163262.83456.6d. PMID 15790935. http://atvb.ahajournals.org/cgi/content/full/25/6/1102. 
  7. ^ Lau D, Baldus S (July 2006). "Myeloperoxidase and its contributory role in inflammatory vascular disease". Pharmacol. Ther. 111 (1): 16–26. doi:10.1016/j.pharmthera.2005.06.023. PMID 16476484. 
  8. ^ 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.
  9. ^ Heslop CL, Frohlich JJ, Hill JS. Myeloperoxidase and C-reactive protein have combined utility for long-term prediction of cardiovascular mortality after coronary angiography. J Am Coll Cardiol 2010; 55: 1102-9. PMID 20223364.
  10. ^ Kagan VE, Konduru NV, Feng W, Allen BL, Conroy J, Volkov Y, Vlasova II, Belikova NA, Yanamala N, Kapralov A, Tyurina YY, Shi J, Kisin ER, Murray AR, Franks J, Stolz D, Gou P, Klein-Seetharaman J, Fadeel B, Star A, Shvedova AA (April 2010). "Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation". Nat Nanotechnol 5 (5): 354–9. doi:10.1038/nnano.2010.44. PMID 20364135. Lay summary – popsci.com. 

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Look at other dictionaries:

  • Myeloperoxidase — Vorhandene Strukturdaten: s. UniProt Masse/Länge …   Deutsch Wikipedia

  • Myeloperoxidase — Myéloperoxidase La myéloperoxidase est une enzyme halogénodependante active contre E. coli et L. acidophilus pour des pH acides (= 5). L ajout de peroxyde n est pas nécessaire pour Lactobacillus puisque ce dernier le produit lui même. L halogène… …   Wikipédia en Français

  • Myéloperoxidase — La myéloperoxidase est une enzyme halogénodependante active contre E. coli et L. acidophilus pour des pH acides (= 5). L ajout de peroxyde n est pas nécessaire pour Lactobacillus puisque ce dernier le produit lui même. L halogène le plus efficace …   Wikipédia en Français

  • myeloperoxidase — A metallo enzyme containing iron, found in the lysosomal granules of myeloid cells, particularly macrophages and neutrophils; responsible for generating potent bacteriocidal activity by the hydrolysis of hydrogen peroxide (produced in the… …   Dictionary of molecular biology

  • myeloperoxidase — noun A peroxidase enzyme most abundantly present in neutrophil granulocytes, responsible for the greenish colour of pus and mucus …   Wiktionary

  • myeloperoxidase — A peroxidase occurring in phagocytic cells that can oxidize halogen ions ( e.g., I−) to the free halogen; an autosomal recessive deficiency of m. leads to impaired bacterial killing. * * * my·e·lo·per·ox·i·dase .mī ə lō pə räk sə .dās, .dāz …   Medical dictionary

  • myeloperoxidase — my·elo·peroxidase …   English syllables

  • myeloperoxidase — ˌ noun Etymology: myel + peroxidase : a peroxidase of phagocytic cells (as neutrophils and monocytes) that is held to assist in bactericidal activity by catalyzing the oxidation of ionic halogen to free halogen …   Useful english dictionary

  • Myeloperoxidase deficiency — Classification and external resources Hypochlorous acid is normally produced by myeloperoxidase OMIM …   Wikipedia

  • myeloperoxidase (MPO) deficiency — my·elo·per·ox·i·dase (MPO) de·fi·cien·cy (mi″ə lo pər okґsĭ dās) an autosomal recessive disorder caused by mutation in the myeloperoxidase gene (MPO, locus:17q23.1), characterized by the complete absence of MPO in… …   Medical dictionary


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