Myeloperoxidase

Myeloperoxidase
Existing structural data: s. UniProt
Properties of human protein
Mass / length primary structure	150 k Da / 2 x 114 + 2 x 467 = 1162 amino acids
Secondary to quaternary structure	Heterotetramer (2L + 2H)
Cofactor	2 Ca 2+ , 2 hems b
Precursor	(697 aa)
Isoforms	3
Identifier
Gene name	MPO
External IDs	OMIM :  606989 UniProt :  P05164
Enzyme classification
EC, category	1.11.1.7 ,  oxidoreductase
Response type	Redox reaction
Substrate	Donor + H 2 O 2
Products	Ox. Donor + H 2 O
Occurrence
Homology family	Eosinophil peroxidase
Parent taxon	Chordates
Orthologue (human)
Entrez	4353
Ensemble	ENSG00000005381
UniProt	P05164
Refseq (mRNA)	NM_000250
Refseq (protein)	NP_000241
Gene locus	Chr 17: 58.27 - 58.28 Mb
PubMed search	4353

Myeloperoxidase (MPO) is an enzyme in neutrophilic granulocytes of chordates that plays an important role in the regulation and termination of inflammatory processes. The enzyme catalyzes the oxidation of chloride ions with the help of hydrogen peroxide :

${\displaystyle H_{\mathrm {2} }O_{\mathrm {2} }+Cl^{-}\rightarrow H_{\mathrm {2} }O+ClO^{-}}$

The hypochlorite ions formed oxidize various biomolecules and thus contribute to the recognition and uptake of apoptotic material by phagocytes .

Occurrence

Myeloperoxidase is expressed in neutrophil granulocytes , monocytes , various tissue macrophages such as Kupffer's stellate cells and cells of the microglia as well as in nerve cells in Alzheimer's patients . In neutrophils and monocytes, MPO can make up 1-5% of the total amount of cellular protein and is stored in leukocytes in azurophilic granules. After phagocyte activation, MPO is secreted into phagolysosomal compartments and into the extracellular space. The absorption properties of the MPO contribute significantly to the greenish-yellow color of the pus .

properties

Myeloperoxidase is a 150 kDa protein that consists of 2 small (15 kDa each) and 2 large subunits, of which at least 3 isoforms of 57, 59 and 60 kDa in size exist. MPO is rich in arginine and therefore basic . With an IP value> 10, MPO is strongly cationic at neutral pH . MPO belongs to a group of peroxidases that share a covalently bound, curved heme . The MPO is heme M derived from heme b , which is also known as green heme because of its absorption properties. The methyl carbon of the heme C ring is esterified with Asp-94 of the protein, the methyl carbon of the heme A ring is esterified with the carboxylate oxygen of Glu-242. The terminal carbon atom of the vinyl group of the A-ring is ionically bonded to the sulfur atom of Met-243. The heme M of the MPO is bent by 14 ° along an imaginary axis through the A and C rings of the heme.

Functions

Catalytic activity

During the oxidative burst of neutrophils from MPO forms hydrogen peroxide (H ₂ O ₂ ), and chloride and bromide anions (Cl ^- , Br ^- ), chlorine (Cl ₂ ), bromine (Br ₂ ), and bromine chloride (BrCl). Under physiological conditions, it immediately forms hypochlorite (HClO) and hypobromite (HBrO). In addition to halides, the MPO-I form also oxidizes nitrite (NO ₂ ), nitrogen monoxide (NO), thiocyanate (SCN ^- ) and tyrosine .

Effect on biomolecules

The reactive hypochlorite reacts with a large number of oxidizable biomolecules that contain unsaturated double bonds, thiols or various nitrogen components. The main chlorination reactions take place with pyridine nucleotides (e.g. NAD ⁺ ), cholesterol and unsaturated fatty acids with the formation of chlorohydrins and with amino groups with the formation of chloramines. In effect, MPO activity causes e.g. B. cholesterol-rich LDL is oxidized, membrane lipids are oxidized and Tyr residues of proteins are made reactive, all processes that have at least a regulatory function.

Role in inflammation

For electrostatic reasons, myeloperoxidase binds to phosphatidylserine and thus specifically to the outer membrane of apoptotic cells.

Role in infection

Contrary to what was previously assumed, MPO does not seem to have any general antimicrobial effect. Although a role of the halogenated products formed by the MPO in the chemical control of infectious particles appears plausible, MPO knockout mice and people with MPO deficiency do not show any increased susceptibility to bacterial infections. Only infections with the fungus Candida albicans occur more frequently in these individuals.

genetics

The human MPO gene is located on chromosome 17 , locus 17q23.1.

Diseases

MPO deficiency

There is currently no evidence-based data showing that patients with MPO deficiency show an increased susceptibility to Candida albicans infections and a generally increased risk of inflammation. Most of the publications cannot show an increased occurrence of infections in the majority of patients.

Antibodies to MPO

If autoantibodies against MPO are formed, these antibodies appear as so-called perinuclear antineutrophilic cytoplasmic antibodies pANCAs . These play a role in various vasculitides such as Churg-Strauss syndrome and rapidly progressive glomerulonephritis .

Myeloperoxidase as a biomarker for joint diseases in horses

Myeloperoxidase activity is increased in the synovia of joints with septic arthritis in horses compared to healthy joints and joints with non-septic diseases.

Individual evidence

1. ^ Pattie S. Green, Armando J. Mendez, Jason S. Jacob, Jan R. Crowley, Whit Growdon ,: Neuronal expression of myeloperoxidase is increased in Alzheimer's disease . In: Journal of Neurochemistry . tape 90 , 2004, p. 724-733 , doi : 10.1111 / j.1471-4159.2004.02527.x .
2. ^ R. Fenna, J. Zeng, C. Davey: Structure of the green heme in myeloperoxidase. In: Archives of Biochemistry and Biophysics . Volume 316, Number 1, January 1995, pp. 653-656, doi : 10.1006 / abbi.1995.1086 , PMID 7840679 .
3. ↑ Jürgen Arnhold, Paul G. Furtmüller, Günther Regelsberger, Christian Obinger: Redox properties of the couple compound I / native enzyme of myeloperoxidase and eosinophil peroxidase . In: FEBS (Ed.): European Journal of Chemistry . tape 268 , 2001, p. 5142-5148 .
4. ↑ Ernst Malle, Thomas Buch, Herrmann-Josef Grone: Myeloperoxidase in kidney disease . In: Kidney International . tape 64 , 2003, p. 1956-1967 .
5. ↑ Lanza F: Clinical manifestation of myeloperoxidase deficiency . In: J Mol Med . 76, No. 10, September 1998, pp. 676-81. PMID 9766845 .
6. ↑ A. Moschos: Synovial examinations in horses - with special consideration of the Myeloperoxidaes activity in the synovial membrane of diseased joints and tendon sheaths . Vet med Diss., Free University Berlin 2007; on-line