Myeloperoxidase

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Myeloperoxidase

Myeloperoxidase (MPO) is a peroxidase

Peroxidase

Peroxidases are a large family of enzymes. A majority of peroxidase protein sequences can be found in the PeroxiBase database. Peroxidases typically catalyze a reaction of the form:...
enzyme

Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
most abundantly present in neutrophil granulocyte

Neutrophil granulocyte

Neutrophil granulocytes, generally referred to as neutrophils, are the most abundant type of white blood cells in humans and form an essential part of the immune system....
s (a subtype of white blood cell

White blood cell

White blood cells , or leukocytes , are cell of the immune system defending the body against both infectious disease and foreign materials....
s). It is a lysosomal

Lysosome

Lysosomes are organelles that contain digestive enzymes . Some biologists say they can only be found in animal cells, but there is new evidence that supports that they may exist in plant cells....
protein stored in azurophilic granules of the neutrophil. MPO has a heme

Heme

A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin....
pigment, which causes its green color in secretions rich in neutrophils, such as pus

Pus

Pus is a whitish-yellow, yellow or yellow-brown substance produced during inflammatory pyogenic bacteriuml infection. An accumulation of pus in an enclosed tissue space is known as an abscess....
and some forms of mucus

Mucus

In vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. It is a viscous colloid containing antiseptic enzymes and immunoglobulins that serves to protect Epithelium in the respiratory,...
.

150-kDa

KDA

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Structure

The 150-kDa

KDA

KDA may refer to:* Kongsberg Defence & Aerospace* Kotelawala Defence Academy* Kramer Design Associates* Lithium diisopropylamide, KDA is the potassium analogue of lithium diisopropylamide...
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. 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

Hypochlorous acid

Hypochlorous acid is a weak acid with the chemical formula HClO. It bonds when chlorine dissolves in water. It cannot be isolated in pure form due to rapid equilibration with its precursor ....
(HOCl) from hydrogen peroxide

Hydrogen peroxide

Hydrogen peroxide is a very pale blue liquid which appears colorless in a dilute solution, slightly more viscous than water. It is a weak acid....
(H₂O₂) and chloride

Chloride

The chloride ion is formed when the chemical element chlorine picks up one electron to form an anion Cl−....
anion (Cl^-) (or the equivalent from a non-chlorine halide) during the neutrophil's respiratory burst

Respiratory burst

Respiratory burst is the rapid release of reactive oxygen species from different types of Cell .Usually it denotes the release of these chemicals from immune cells, e.g., neutrophil granulocytes and macrophages, as they come into contact with different bacterium or fungus....
. It requires heme

Heme

A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin....
as a cofactor. Furthermore, it oxidizes tyrosine to tyrosyl radical using hydrogen peroxide

Hydrogen peroxide

Hydrogen peroxide is a very pale blue liquid which appears colorless in a dilute solution, slightly more viscous than water. It is a weak acid....
as oxidizing agent.

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

Bacteria

The Bacteria are a large group of unicellular microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals....
and other pathogen

Pathogen

A pathogen , infectious agent, or germ, is a biological agent that causes disease or illness to its Host .There are several substrates and pathways whereby pathogens can invade a host; the principal pathways have different episodic time frames, but soil contamination has the longest or most persistent potential for harboring...
s.

Genetics

The gene

Gene

A gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cell and pass genetic trait to offspring....
is located on chromosome

Chromosome

A chromosome is an organized structure of DNA and protein that is found in Cell . A chromosome is a single piece of DNA that contains many genes, regulatory sequence and other genetic sequence....
17 (17q23.1).

Role in disease

Myeloperoxidase deficiency

Myeloperoxidase deficiency is a common genetic disorder featuring deficiency, either in quantity or function, of myeloperoxidase, an enzyme found in certain phagocyte immune cells, especially polymorphonuclear leukocytes....
is a hereditary deficiency of the enzyme, which predisposes to immune deficiency.

Antibodies

Antibody

Antibodies are gamma globulin proteins that are found in blood or other bodily fluids of vertebrates, and are used by the immune system to identify and neutralize foreign objects, such as bacterium and viruses....
against MPO have been implicated in various types of vasculitis

Vasculitis

Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels.Both arteries and veins are affected....
, most prominently crescentic glomerulonephritis

Glomerulonephritis

Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a kidney disease characterized by inflammation of the glomerulus, or small blood vessels in the kidneys....
and Churg-Strauss syndrome

Churg-Strauss syndrome

Churg-Strauss syndrome is a medium and small vessel autoimmune disease vasculitis, leading to necrosis. It involves mainly the blood vessels of the lungs , gastrointestinal system, and peripheral nerves, but also affects the heart, skin and kidneys....
. They are detected as perinuclear ANCAs

Anti-neutrophil cytoplasmic antibody

Anti-neutrophil cytoplasmic antibodies are a group of mainly IgG antibodies against antigens in the cytoplasm of neutrophil granulocytes and monocytes....
(pANCAs), as opposed to the cytoplasmic ANCAs (cANCAs) against proteinase 3

Proteinase 3

Proteinase 3 also known as PRTN3 is an enzyme which in humans is encoded by the PRTN3 gene....
(PR3), which are strongly associated with Wegener's granulomatosis

Wegener's granulomatosis

Wegener's granulomatosis is a form of vasculitis that affects the lungs, kidneys and other organs. Due to its end-organ damage, it can be a serious disease that requires long-term immune suppression....
.

Diagnostic use

Routine testing of MPO is not performed. A 2003 study suggested that it could serve as a sensitive predictor for myocardial infarction

Myocardial infarction

Myocardial infarction , commonly known as a heart attack, occurs when the Blood flow to part of the heart is interrupted. This is most commonly due to occlusion of a coronary artery following the rupture of a Vulnerable plaque, which is an unstable collection of lipids and white blood cells in the wall of an artery....
in patients presenting with chest pain

Chest pain

In medicine, chest pain is a symptom of a number of serious conditions and is generally considered a medical emergency. Even though it may be determined that the chest pain is non-cardiac in origin this is often a diagnosis of exclusion made after ruling out more serious causes of pain....
. At present, 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.

Immunohistochemical

Immunohistochemistry

Immunohistochemistry or IHC refers to the process of localizing proteins in cells of a tissue section exploiting the principle of antibody binding specifically to antigens in biological tissues....
staining for myeloperoxidase used to be administered in the diagnosis of acute myeloid leukemia

Acute myeloid leukemia

Acute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of white blood cells, characterized by the rapid proliferation of abnormal cells which accumulate in the bone marrow and interfere with haematopoiesis....
to demonstrate that the leukemic cells were derived from the myeloid

Myeloid

The term myeloid suggests an origin in the bone marrow or spinal cord, or a resemblance to the marrow or spinal cord.In hematopoiesis, the term "myeloid cell" is used to describe any leukocyte that is not a lymphocyte....
lineage. However, the use of myeloperoxidase staining in this setting has been supplanted by the widespread use of flow cytometry

Flow cytometry

Flow cytometry is a technique for counting, examining, and sorting microscopic particles suspended in a stream of fluid. It allows simultaneous Parametric model analysis of the physical and/or chemical characteristics of single cells flowing through an optical and/or electronic detection apparatus....
. Myeloperoxidase staining is still important in the diagnosis of extramedullary leukemia, or chloroma.

Myeloperoxidase

Structure

Function

Genetics

Role in disease

Diagnostic use

See also