WordNet

any of a group of enzymes (occurring especially in plant cells) that catalyze the oxidation of a compound by a peroxide

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/11/04 08:44:55」(JST)

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Myeloperoxidase (MPO) is a peroxidase enzyme that in humans is encoded by the MPO gene.^[2] Myeloperoxidase is most abundantly expressed in neutrophil granulocytes (a subtype of white blood cells).^[3] 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.

Structure[edit]

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 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[edit]

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.^[5]

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

Inhibitors of MPO[edit]

Azide has been used traditionally as an MPO inhibitor, but 4-aminobenzoic acid hydrazide (4-ABH) is a more specific inhibitor of MPO.^[6]

Genetics[edit]

The human gene is located on chromosome 17 (17q23.1).^[2]

Role in disease[edit]

Myeloperoxidase deficiency is a hereditary deficiency of the enzyme, which predisposes to immune deficiency.^[7]

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 (p-ANCAs), as opposed to the cytoplasmic ANCAs (c-ANCAs) 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.^[8] It has been suggested that myeloperoxidase plays a significant role in the development of the atherosclerotic lesion and rendering plaques unstable.^[9]^[10]

Medical uses[edit]

An initial 2003 study suggested that MPO could serve as a sensitive predictor for myocardial infarction in patients presenting with chest pain.^[11] 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.^[12]

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.^{[citation needed]} Myeloperoxidase staining is still important in the diagnosis of myeloid sarcoma, contrasting with the negative staining of lymphomas, which can otherwise have a similar appearance.^[13]

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.^[14]

References[edit]

^ PDB 1D7W; Blair-Johnson M, Fiedler T, Fenna R (November 2001). "Human myeloperoxidase: structure of a cyanide complex and its interaction with bromide and thiocyanate substrates at 1.9 Å resolution". Biochemistry 40 (46): 13990–7. doi:10.1021/bi0111808. PMID 11705390.
^ ^a ^b "Entrez Gene: Myeloperoxidase".
^ Klebanoff SJ (May 2005). "Myeloperoxidase: friend and foe". J. Leukoc. Biol. 77 (5): 598–625. doi:10.1189/jlb.1204697. PMID 15689384.
^ Mathy-Hartert M, Bourgeois E, Grülke S, Deby-Dupont G, Caudron I, Deby C, Lamy M, Serteyn D (April 1998). "Purification of myeloperoxidase from equine polymorphonuclear leucocytes". Can. J. Vet. Res. 62 (2): 127–32. PMC 1189459. PMID 9553712.
^ Heinecke JW, Li W, Francis GA, Goldstein JA (June 1993). "Tyrosyl radical generated by myeloperoxidase catalyzes the oxidative cross-linking of proteins". J. Clin. Invest. 91 (6): 2866–72. doi:10.1172/JCI116531. PMC 443356. PMID 8390491.
^ 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.
^ Kutter D, Devaquet P, Vanderstocken G, Paulus JM, Marchal V, Gothot A (2000). "Consequences of total and subtotal myeloperoxidase deficiency: risk or benefit ?". Acta Haematol. 104 (1): 10–5. PMID 11111115.
^ Zhang R, Brennan ML, Fu X, Aviles RJ, Pearce GL, Penn MS, Topol EJ, Sprecher DL, Hazen SL (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.
^ 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.
^ 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.
^ Brennan ML, Penn MS, Van Lente F, Nambi V, Shishehbor MH, Aviles RJ, Goormastic M, Pepoy ML, McErlean ES, Topol EJ, Nissen SE, Hazen SL (October 2003). "Prognostic value of myeloperoxidase in patients with chest pain". N. Engl. J. Med. 349 (17): 1595–604. doi:10.1056/NEJMoa035003. PMID 14573731.
^ Heslop CL, Frohlich JJ, Hill JS (March 2010). "Myeloperoxidase and C-reactive protein have combined utility for long-term prediction of cardiovascular mortality after coronary angiography". J. Am. Coll. Cardiol. 55 (11): 1102–9. doi:10.1016/j.jacc.2009.11.050. PMID 20223364.
^ Leong A S-Y, Cooper K, Leong, FJ W-M (2003). Manual of Diagnostic Antibodies for Immunohistology. London: Greenwich Medical Media. pp. 325–326. ISBN 1-84110-100-1.
^ 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.

UpToDate Contents

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1. 免疫不全症を引き起こすミエロペルオキシダーゼ欠損症および酵素白血球欠損症 myeloperoxidase deficiency and other enzymatic wbc defects causing immunodeficiency
2. 心血管疾患と同等のリスクと確立した危険因子の概要 overview of the risk equivalents and established risk factors for cardiovascular disease
3. 抗好中球細胞質抗体の臨床的な意味 clinical spectrum of antineutrophil cytoplasmic antibodies
4. 貧食細胞機能の原発性疾患：概要 primary disorders of phagocytic function an overview
5. 小児および思春期における好中球減少症の概要 overview of neutropenia in children and adolescents

English Journal

Protective effects of Ziyang tea polysaccharides on CCl4-induced oxidative liver damage in mice.

Wang D, Zhao Y, Sun Y, Yang X.SourceKey Laboratory of Ministry of Education for Medicinal Resource and Natural Pharmaceutical Chemistry, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710062, China.
Food chemistry.Food Chem.2014 Jan 15;143:371-8. doi: 10.1016/j.foodchem.2013.08.005. Epub 2013 Aug 11.
This study was designed to investigate the hepatoprotective effects of the tea polysaccharides (ZTPs) extracted from a selenium-enriched Ziyang green tea (Camellia sinensis). ZTPs were identified as the heteropolysaccharides with glucose (31.4%), arabinose (23.5%) and galactose (21.8%) being the mai
PMID 24054254

An assay for pro-oxidant reactivity based on phenoxyl radicals generated by laccase.

Moţ AC, Coman C, Miron C, Damian G, Sarbu C, Silaghi-Dumitrescu R.SourceDepartment of Chemistry and Chemical Engineering, "Babes-Bolyai" University, 1 Mihail Kogălniceanu Str, Cluj-Napoca RO-400084, Romania. Electronic address: augustinmot@chem.ubbcluj.ro.
Food chemistry.Food Chem.2014 Jan 15;143:214-22. doi: 10.1016/j.foodchem.2013.07.128. Epub 2013 Aug 3.
A transient species may be detected with UV-vis and EPR spectroscopy during turnover of a laccase with quercetin; this species is assigned as a quercetin-derived radical, based on EPR spectra as well the observed UV-vis similarities (a 540nm centred band) with previously reported data. The rates of
PMID 24054233

Carbamylation of LDL and its relationship with myeloperoxidase in Type 2 diabetes mellitus.

Shiu SW, Xiao SM, Wong Y, Chow WS, Lam KS, Tan KC.Source*Department of Medicine, University of Hong Kong, Hong Kong.
Clinical science (London, England : 1979).Clin Sci (Lond).2014 Jan 1;126(2):175-81. doi: 10.1042/CS20130369.
LDL (low-density lipoprotein) is subjected to pro-atherogenic modifications in the circulation. A novel uraemia-independent mechanism of carbamylation of lipoproteins mediated by MPO (myeloperoxidase) has recently been reported. We have investigated whether carbamylation of LDL was increased in pati
PMID 23905837

Japanese Journal

The relationship between exposure to microbial volatile organic compound and allergy prevalence in single-family homes.

Araki Atsuko,Kanazawa Ayako,Kawai Toshio,Eitaki Yoko,Morimoto Kanehisa,Nakayama Kunio,Shibata Eiji,Tanaka Masatoshi,Takigawa Tomoko,Yoshimura Takesumi,Chikara Hisao,Saijo Yasuaki,Kishi Reiko
The Science of the total environment 423, 18-26, 2012-04-15
… Exposure to 1-octen-3-ol, one of the known MVOCs, has been reported to reduce nasal patency and increase nasal lavage myeloperoxidase, eosinophil cationic proteins, and lysozymes in both experimental and field studies. …
NAID 120004027252

Eating Buckwheat Cookies Is Associated with the Reduction in Serum Levels of Myeloperoxidase and Cholesterol : A Double Blind Crossover Study in Day-Care Centre Staffs

WIESLANDER Gunilla,FABJAN Nina,VOGRINCIC Maja,KREFT Ivan,JANSON Christer,SPETZ-NYSTROM Ulrike,VOMBERGAR Blanka,TAGESSON Christer,LEANDERSON Per,NORBACK Dan
Tohoku journal of experimental medicine 225(2), 123-130, 2011-10-01
NAID 10029665931

Related Pictures

★リンクテーブル★

リンク元	「白血球」「アズール顆粒」「ミエロペルオキシダーゼ」「peroxidase」「MPO」

「白血球」

Myeloperoxidase
	; Crystallographic structure of human myeloperoxidase.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1CXP, 1D2V, 1D5L, 1D7W, 1DNU, 1DNW, 1MHL, 1MYP, 3F9P, 3ZS0, 3ZS1, 4DL1, 4EJX
Identifiers
Symbol	MPO
External IDs	OMIM: 606989 MGI: 97137 HomoloGene: 55450 ChEMBL: 2439 GeneCards: MPO Gene
EC number	1.11.2.2
Gene Ontology
Molecular function	• chromatin binding; • peroxidase activity; • heparin binding; • heme binding; • metal ion binding;
Cellular component	• extracellular space; • nucleus; • mitochondrion; • lysosome; • secretory granule;
Biological process	• response to yeast; • hypochlorous acid biosynthetic process; • respiratory burst involved in defense response; • defense response; • response to oxidative stress; • removal of superoxide radicals; • low-density lipoprotein particle remodeling; • hydrogen peroxide catabolic process; • negative regulation of apoptotic process; • negative regulation of growth of symbiont in host; • defense response to fungus; • oxidation-reduction process;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

Search
PMC	articles
PubMed	articles
NCBI	proteins

Myeloperoxidase
Identifiers
EC number	1.11.2.2
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Search
PMC	articles
PubMed	articles
NCBI	proteins

　　[★]

英: leukocyte, leucocyte (Z), white blood cell (Z), WBC, white corpuscle, white cell
関: 赤血球、血球、血液

白血球

顆粒球

基準値

4000-9000 (/μl)　(2007前期解剖学授業プリント)

異常値の出るメカニズム第5版

5000- 8400 (/μl) (健常者の2/3)
4500-11000 (/μl) (95%範囲)

年齢との関連

新生児期>幼児期>成人期(20歳までに成人値)
妊婦でも増加(妊娠#妊娠による変化)

生理的な変動

精神的ストレス↑　　→　交感神経の刺激により好中球の血管壁遊離が促進されるため
午前↓、午後↑

基準値

			07解	異メ	流マ		HIM.A-1
顆粒球	好中球	桿状核球	40～70	44～66	40～60	4～14	0～5
		分葉核球				43～59	40～70
	好酸球		2～4	0～ 4	2～4		0～6
	好塩基球		0～2	0～0.5	0～2		0～2
無顆粒球	リンパ球		25～40	30～38	26～40		20～50
	単球		3～6	0～ 5	3～6		4～8

07解: 2007前期解剖学授業プリント
異メ: 異常値の出るメカニズム第5版 p.91
流マ: 流れが分かる実践検査マニュアル上巻 p.10

血管外滲出 extravasation (SMB.37 BPT.37)

(margination)

1. 赤血球は軽く早く流れるので血管の中央をながれ、白血球は血管のへりを流れている

(rolling)

2. IL-1, TNFで血管内皮細胞が活性化し、血管内腔にE-selectinを発現する
3. P-selectinはヒスタミンやトロンビンの働きにより、血管内腔に発現する
4. 白血球と血管内皮細胞の接着分子で接着することで、白血球がrollingを始める
3. 次第にselectinによる接着はdown regulateされる

(adheresion & arrested)

4. 炎症部位から出されたケモカインが血管内皮細胞の表面ののペプチドグリカンに結合し、白血球に提示される
5. 白血球表面のインテグリンが活性化し、血管内皮細胞のICAM-1, VCAM-1と強く結合する

(transmigration)

6. 白血球と血管内皮細胞に発現しているPECAM-1(CD31)がお互い接着し、白血球が血管内皮細胞の間隙を通って細胞外マトリックスに入る

血管内皮細胞		白血球
Rolling
E-selectin	－	糖鎖(SLe^x)
P-selectin	－	糖鎖
糖鎖(GlyCAM-1)(=CD34)	－	L-selectin
Adhestion
ICAM-1	－	LFA-1 integlin(CD11a/CD18), Mac-1 integlin(CD11b/CD18)
VCAM-1	－	VLA-1 integlin
transmigration
PECAM-1(CD31)	－	PECAM-1(CD31)

白血球の染色

ギムザ染色

好酸性：赤く染まる→ヘモグロビン
好塩基性：青く染まる→リボソーム、核内のヒストン蛋白
好酸性でも好塩基性でもない：淡いピンクに染まる

MPO myeloperoxidase反応（染色）

MPOをもつ：顆粒球（前骨髄球～分葉核球）、単球（前単球～単球）
MPOをもたない：リンパ球系細胞

エステラーゼ esterase

好中球：長鎖エステルを分解
単球：短鎖エステルを分解

関節液

　　炎症感染
200 2000 20000
500 5000 50000

臨床関連

LAD(leukocyte adhesion deficiency)症候群 (SMB.37)

白血球のインテグリンが欠損または減少する先天性疾患

反復性の細菌皮膚感染

SIRSの診断基準：＜4,000/ul or ＞12,000/ul

「アズール顆粒」

　　[★]

英: azurophilic granule
関: 顆粒、白血球

概念

医学辞書

アズールによって赤紫色に染色される細胞質内の顆粒で、血液細胞(顆粒球、単球、リンパ球)にみられる。顆粒球において顕著で、前骨髄球段階から出現。

アズール好性
アズール→紫褐、紫赤
リンパ球、単球、前骨髄球、血小板、巨核球
リンパ球では0.3-0.6μm

顆粒内に含まれる物質

ファゴリソソーム形成された後の殺菌に必要な成分が貯蔵されている
ミエロペルオキシダーゼ
デフェンシン
セルプロシディン
BPI(=CAP57)

BPT.39

NADPH　+ O₂　－(NADPH oxidase)→ O₂^-･ (superoxide)
O₂^-･　－(spontaneous dismutation)→ H₂O₂ (gydrogen peroxide)
H₂O₂ －(myeloperoxidase)→ HOCl^･

「ミエロペルオキシダーゼ」

　　[★]

英: myeloperoxidase, MPO
関: oxidative burst、ペルオキシダーゼ染色

「peroxidase」

　　[★] ペルオキシダーゼ、過酸化酵素

関: myeloperoxidase

「MPO」

　　[★] ミエロペルオキシダーゼ myeloperoxidase

[pmid11705390-1] PDB 1D7W; Blair-Johnson M, Fiedler T, Fenna R (November 2001). "Human myeloperoxidase: structure of a cyanide complex and its interaction with bromide and thiocyanate substrates at 1.9 Å resolution". Biochemistry 40 (46): 13990–7. doi:10.1021/bi0111808. PMID 11705390.

[entrez-2] "Entrez Gene: Myeloperoxidase".

[pmid15689384-3] Klebanoff SJ (May 2005). "Myeloperoxidase: friend and foe". J. Leukoc. Biol. 77 (5): 598–625. doi:10.1189/jlb.1204697. PMID 15689384.

[pmid9553712-4] Mathy-Hartert M, Bourgeois E, Grülke S, Deby-Dupont G, Caudron I, Deby C, Lamy M, Serteyn D (April 1998). "Purification of myeloperoxidase from equine polymorphonuclear leucocytes". Can. J. Vet. Res. 62 (2): 127–32. PMC 1189459. PMID 9553712.

[pmid8390491-5] Heinecke JW, Li W, Francis GA, Goldstein JA (June 1993). "Tyrosyl radical generated by myeloperoxidase catalyzes the oxidative cross-linking of proteins". J. Clin. Invest. 91 (6): 2866–72. doi:10.1172/JCI116531. PMC 443356. PMID 8390491.

[pmid9020887-6] 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.

[pmid11111115-7] Kutter D, Devaquet P, Vanderstocken G, Paulus JM, Marchal V, Gothot A (2000). "Consequences of total and subtotal myeloperoxidase deficiency: risk or benefit ?". Acta Haematol. 104 (1): 10–5. PMID 11111115.

[pmid11694155-8] Zhang R, Brennan ML, Fu X, Aviles RJ, Pearce GL, Penn MS, Topol EJ, Sprecher DL, Hazen SL (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.

[pmid15790935-9] 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.

[pmid16476484-10] 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.

[pmid14573731-11] Brennan ML, Penn MS, Van Lente F, Nambi V, Shishehbor MH, Aviles RJ, Goormastic M, Pepoy ML, McErlean ES, Topol EJ, Nissen SE, Hazen SL (October 2003). "Prognostic value of myeloperoxidase in patients with chest pain". N. Engl. J. Med. 349 (17): 1595–604. doi:10.1056/NEJMoa035003. PMID 14573731.

[pmid20223364-12] Heslop CL, Frohlich JJ, Hill JS (March 2010). "Myeloperoxidase and C-reactive protein have combined utility for long-term prediction of cardiovascular mortality after coronary angiography". J. Am. Coll. Cardiol. 55 (11): 1102–9. doi:10.1016/j.jacc.2009.11.050. PMID 20223364.

[Leong_2003-13] Leong A S-Y, Cooper K, Leong, FJ W-M (2003). Manual of Diagnostic Antibodies for Immunohistology. London: Greenwich Medical Media. pp. 325–326. ISBN 1-84110-100-1.

[pmid20364135-14] 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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検索

案内

案内

myeloperoxidase