MPO Human
Description
Structure and Biosynthesis
MPO is a 150-kDa glycoprotein encoded by the MPO gene on chromosome 17 (q21.3-q23) . It exists as a homodimer of two heterodimers, each consisting of:
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Heavy chain (59 kDa): Contains a heme group and calcium ions critical for catalysis.
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Light chain (14.5 kDa): Linked via disulfide bonds to the heavy chain and glycosylated.
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Prosthetic heme group: Covalently bound via ester and sulfonium ion linkages to aspartate, glutamate, and methionine residues .
ProMPO (precursor form) includes an additional propeptide that blocks dimerization by forming a disulfide bridge (Cys-158–Cys-319) . Maturation involves proteolytic cleavage of the propeptide in the Golgi apparatus, enabling dimerization via Cys-319–Cys-319 interchain bonds .
| Feature | ProMPO | Mature MPO |
|---|---|---|
| Dimerization | Blocked by propeptide | Active via Cys-319–Cys-319 bridge |
| Heme cavity | Fully formed | Identical to proMPO |
| Substrate access | Restricted by propeptide | Unrestricted |
| Localization | ER/Golgi (during synthesis) | Azurophilic granules (neutrophils) |
Enzymatic Function and Mechanism
MPO catalyzes the oxidation of chloride ions to hypochlorous acid (HOCl) via hydrogen peroxide (H₂O₂) :
This reaction proceeds through two intermediates:
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Compound I: A high-valent iron-oxo intermediate formed by H₂O₂ oxidation.
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Compound II: A reduced iron intermediate after chloride oxidation .
HOCl mediates microbial killing by:
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Oxidizing bacterial components (e.g., DNA, lipids).
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Generating 3-chlorotyrosine and other halogenated proteins .
Key Substrates and Byproducts
| Substrate | Product | Biological Impact |
|---|---|---|
| H₂O₂ | HOCl | Microbial killing, tissue oxidation |
| Tyrosine | Tyrosyl radical | Protein crosslinking (dityrosine) |
| LDL cholesterol | Oxidized LDL | Atherosclerosis progression |
| ApoA-I (HDL) | Dysfunctional HDL | Impaired anti-inflammatory effects |
Clinical Significance and Disease Associations
MPO is a biomarker for inflammation and a therapeutic target in chronic diseases.
Cardiovascular Disease
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Atherosclerosis: MPO oxidizes LDL cholesterol and reduces nitric oxide (NO) bioavailability, promoting endothelial dysfunction .
Neurodegenerative Diseases
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Alzheimer’s Disease: MPO-generated oxidants (e.g., 3-chlorotyrosine) accumulate in amyloid plaques, correlating with cognitive decline .
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Parkinson’s Disease: Upregulated MPO in the ventral midbrain contributes to dopaminergic neuron damage .
Autoimmune and Inflammatory Disorders
MPO Quantification and Diagnostic Applications
MPO levels are measured in clinical settings using ELISA kits and serum/plasma samples .
| Sample Type | MPO Concentration (ng/mL) | Clinical Utility |
|---|---|---|
| Serum | 20–150 (median 57) | Inflammation marker |
| EDTA Plasma | 13–127 (median 32) | Neutrophil activation monitor |
| Heparin Plasma | 25–197 (median 99) | Cardiac ischemia risk assessment |
Therapeutic Implications
Product Specs
Product Science Overview
Myeloperoxidase is encoded by the MPO gene located on chromosome 17 in humans . The enzyme is a lysosomal protein stored in azurophilic granules of neutrophils and is released into the extracellular space during degranulation . The enzyme contains a heme pigment, which gives it a green color in secretions rich in neutrophils, such as mucus and sputum .
MPO catalyzes the production of hypochlorous acid from hydrogen peroxide and chloride ions during the neutrophil’s respiratory burst . This reaction is essential for the microbial killing activity of neutrophils. Additionally, MPO can oxidize tyrosine to form tyrosyl radicals, which are cytotoxic and help in killing bacteria and other pathogens .
Myeloperoxidase deficiency is a documented condition that results in impaired immune function . The enzyme is also involved in various inflammatory processes and has been linked to diseases such as atherosclerosis and certain types of vasculitis . MPO antibodies, known as antineutrophil cytoplasmic antibodies (ANCAs), are useful in diagnosing vasculitis .
Recent studies have shown that myeloperoxidase is the first human enzyme known to break down carbon nanotubes, which has implications for the use of nanotubes in targeted drug delivery . The enzyme’s role in oxidative stress and inflammation continues to be a significant area of research, particularly in understanding its contribution to chronic diseases .
Myeloperoxidase remains a critical enzyme in the study of immunology and pathology, with ongoing research aimed at uncovering its full range of functions and potential therapeutic applications.
