Elastase

Elastase

In molecular biology, elastase is an enzyme from the class of "proteases (peptidases)", that break down proteins.

Forms and classification

There exist two human genes for elastase:
* Pancreatic elastase (ELA-1)
* Neutrophil elastase (ELA-2)

Bacterial forms: Organisms such as "P. aeruginosa" also produce elastase, and is considered a virulence factor.

Function

Elastase breaks down elastin, an elastic fiber that, together with collagen, determines the mechanical properties of connective tissue. The neutrophil form breaks down the "Outer membrane protein A" (OmpA) of "E. coli" and other Gram-negative bacteria, and also breaks down Shigella virulence factors. This is accomplished through the cleavage of peptide bonds in the target proteins. The specific peptide bonds cleaved are those on the carboxy side of small, hydrophobic amino acids such as glycine, alanine, and valine. For more on how this is accomplished, see serine protease.

The role of human elastase in disease

A1AT

Elastase is inhibited by the acute phase protein α1-antitrypsin (A1AT), which binds almost irreversibly to the active site of elastase and trypsin. A1AT is normally secreted by the liver cells into the serum. α1-antitryspin deficiency (A1AD) leads to uninhibited destruction of elastic fiber by elastase; the main result is pulmonary emphysema.

Cyclic hematopoeiesis

The rare disease cyclic hematopoeiesis (also called "cyclic neutropenia") is an autosomal dominant genetic disorder characterised by fluctuating neutrophil granulocyte counts over 21-day periods. During neutropenia, patients are at risk for infections. In 1999, this disease was linked to disorders in the ELA-2 gene. [cite journal |author=Horwitz M, Benson KF, Person RE, Aprikyan AG, Dale DC |title=Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis |journal=Nat. Genet. |volume=23 |issue=4 |pages=433–6 |year=1999 |pmid=10581030 |doi=10.1038/70544] Other forms of congenital neutropenia also appear to be linked to ELA-2 mutations.

Other diseases

Neutrophil elastase is responsible for the blistering in bullous pemphigoid, a skin condition, in the presence of antibodies.

The role of bacterial elastase in disease

Elastase has been shown to disrupt tight junctions, cause proteolytic damage to tissue, break down cytokines and alpha proteinase inhibitor, cleave immunoglobuline A and G (IgA, IgG), and cleave both C3bi, a component of the complement system, and CR1, a receptor on neutrophils for another complement molecule involved in phagocytosis. The cleavage of IgA, IgG, C3bi, and CR1 contributes to a decrease of the ability of neutrophils to kill bacteria by phagocytosis. Together all these factors contribute to human pathology.

References


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  • elastase — noun Etymology: elastin + ase Date: 1949 an enzyme especially of pancreatic juice that digests elastin …   New Collegiate Dictionary

  • elastase — Serine protease that will digest elastin and collagen Type IV; inhibited by alpha 1 protease inhibitor of plasma …   Dictionary of molecular biology

  • elastase — /i las tays, taz/, n. Biochem. a pancreatic protease that catalyzes the hydrolysis of elastin and other related proteins to polypeptides and amino acids. [1945 50; ELAST(IN) + ASE] * * * …   Universalium

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  • Elastase — E|las|ta|se [Kurzw. aus ↑ Elastin u. ↑ ase], die; , n; Syn.: Pankreatopeptidase E: eine Proteinase aus der Bauchspeicheldrüse, die Peptidbindungen insbes. des Elastins spaltet. * * * Elas|ta|se , die; , n [zu ↑ elastisch u. ase = Suffix zur Bez.… …   Universal-Lexikon

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  • Elastase — Elas|ta|se* [ela...] die; , n Kurzw. aus ↑elastisch u. ↑...ase> Enzym, das die Kittsubstanzen der elastischen Muskelfasern abbaut (Biochem.) …   Das große Fremdwörterbuch

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