Elastase
Encyclopedia
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
, elastase is an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
from the class of protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
s (peptidases) that break down protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s.
Forms and classification
There exist eight human geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s for elastase:
| Family | Gene symbol | Protein name | EC number | ||
|---|---|---|---|---|---|
| Approved | Previous | Approved | Previous | ||
| chymotrypsin- like Pancreatic elastase Pancreatic elastase is a form of elastase that is formed in the pancreas. Elastases form a subfamily of serine proteases that hydrolyze many proteins in addition to elastin.... |
CELA1 CELA1 Chymotrypsin-like elastase family member 1 also known as elastase-1 is an enzyme that in humans is encoded by the CELA1 gene.... |
ELA1 | chymotrypsin-like elastase family, member 1 | elastase 1, pancreatic | |
| CELA2A | ELA2A | chymotrypsin-like elastase family, member 2A | elastase 2A, pancreatic | ||
| CELA2B CELA2B Chymotrypsin-like elastase family member 2B is and enzyme that in humans is encoded by the CELA2B gene.- Function :Elastases form a subfamily of serine proteases that hydrolyze many proteins in addition to elastin. Humans have six elastase genes which encode the structurally similar proteins... |
ELA2B | chymotrypsin-like elastase family, member 2B | elastase 2B, pancreatic | ||
| CELA3A | ELA3A | chymotrypsin-like elastase family, member 3A | elastase 3A, pancreatic | ||
| CELA3B CELA3B Chymotrypsin-like elastase family member 3B also known as elastase-3B, protease E, or fecal elastase is an enzyme that in humans is encoded by the CELA3B gene.... |
ELA3B | chymotrypsin-like elastase family, member 3B | elastase 3B, pancreatic | ||
| chymotrypsin Chymotrypsin Chymotrypsin is a digestive enzyme that can perform proteolysis. Chymotrypsin preferentially cleaves peptide amide bonds where the carboxyl side of the amide bond is a tyrosine, tryptophan, or phenylalanine. These amino acids contain an aromatic ring in their sidechain that fits into a... |
CTRC Chymotrypsin-C Chymotrypsin C, also known as caldecrin or elastase 4 is an enzyme that in humans is encoded by the CTRC gene.- Function :Chymotrypsin C is a member of the peptidase S1 family. The encoded protein is a serum calcium-decreasing factor that has chymotrypsin-like protease activity.... |
ELA4 | chymotrypsin C (caldecrin) | elastase 4 | |
| neutrophil | ELANE | ELA2 | neutrophil elastase | elastase 2 | |
| macrophage | MMP12 Matrix metallopeptidase 12 Matrix metalloproteinase-12 also known as macrophage metalloelastase or macrophage elastase is an enzyme that in humans is encoded by the MMP12 gene.- Function :... |
HME | macrophage metalloelastase | macrophage elastase | |
Bacterial forms: Organisms such as P. aeruginosa
Pseudomonas aeruginosa
Pseudomonas aeruginosa is a common bacterium that can cause disease in animals, including humans. It is found in soil, water, skin flora, and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also in hypoxic atmospheres, and has, thus, colonized many...
also produce elastase, and is considered a virulence factor.
Function
Elastase breaks down elastinElastin
Elastin is a protein in connective tissue that is elastic and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched. Elastin is also an important load-bearing tissue in the bodies of...
, an elastic
Elasticity (physics)
In physics, elasticity is the physical property of a material that returns to its original shape after the stress that made it deform or distort is removed. The relative amount of deformation is called the strain....
fiber
Fiber
Fiber is a class of materials that are continuous filaments or are in discrete elongated pieces, similar to lengths of thread.They are very important in the biology of both plants and animals, for holding tissues together....
that, together with collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
, determines the mechanical properties of connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
. The neutrophil form breaks down the Outer membrane protein A (OmpA) of E. coli and other Gram-negative
Gram-negative
Gram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...
bacteria. Elastase also has the important immunological
Immunology
Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. It deals with the physiological functioning of the immune system in states of both health and diseases; malfunctions of the immune system in immunological disorders ; the...
role of breaking down Shigella
Shigella
Shigella is a genus of Gram-negative, nonspore forming, non-motile, rod-shaped bacteria closely related to Escherichia coli and Salmonella. The causative agent of human shigellosis, Shigella causes disease in primates, but not in other mammals. It is only naturally found in humans and apes. During...
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
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
, alanine
Alanine
Alanine is an α-amino acid with the chemical formula CH3CHCOOH. The L-isomer is one of the 20 amino acids encoded by the genetic code. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid...
, and valine
Valine
Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
. For more on how this is accomplished, see serine protease
Serine protease
Serine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...
.
A1AT
Elastase is inhibited by the acute-phase protein α1-antitrypsinAlpha 1-antitrypsin
Alpha 1-Antitrypsin or α1-antitrypsin is a protease inhibitor belonging to the serpin superfamily. It is generally known as serum trypsin inhibitor. Alpha 1-antitrypsin is also referred to as alpha-1 proteinase inhibitor because it inhibits a wide variety of proteases...
(A1AT), which binds almost irreversibly to the active site of elastase and trypsin
Trypsin
Trypsin is a serine protease found in the digestive system of many vertebrates, where it hydrolyses proteins. Trypsin is produced in the pancreas as the inactive proenzyme trypsinogen. Trypsin cleaves peptide chains mainly at the carboxyl side of the amino acids lysine or arginine, except when...
. A1AT is normally secreted by the liver cells into the serum. α1-antitryspin deficiency
Alpha 1-antitrypsin deficiency
Alpha 1-antitrypsin deficiency is an autosomal recessive genetic disorder caused by defective production of alpha 1-antitrypsin , leading to decreased A1AT activity in the blood and lungs, and deposition of excessive abnormal A1AT protein in liver cells...
(A1AD) leads to uninhibited destruction of elastic fiber by elastase; the main result is pulmonary emphysema
Emphysema
Emphysema is a long-term, progressive disease of the lungs that primarily causes shortness of breath. In people with emphysema, the tissues necessary to support the physical shape and function of the lungs are destroyed. It is included in a group of diseases called chronic obstructive pulmonary...
.
Cyclic hematopoeiesis
The rare diseaseRare disease
A rare disease, also referred to as an orphan disease, is any disease that affects a small percentage of the population.Most rare diseases are genetic, and thus are present throughout the person's entire life, even if symptoms do not immediately appear...
cyclic hematopoeiesis
Cyclic neutropenia
Cyclic neutropenia is a form of neutropenia that tends to occur every three weeks and lasting three to six days at a time due to changing rates of cell production by the bone marrow....
(also called "cyclic neutropenia") is an autosomal dominant genetic disorder
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
characterised by fluctuating neutrophil granulocyte
Neutrophil granulocyte
Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They are generally referred to as either neutrophils or polymorphonuclear neutrophils , and are subdivided into segmented neutrophils and banded neutrophils...
counts over 21-day periods. During neutropenia
Neutropenia
Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
, patients are at risk for infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s. In 1999, this disease was linked to disorders in the ELA-2 / ELANE gene. Other forms of congenital neutropenia
Neutropenia
Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
also appear to be linked to ELA-2 mutations.
Other diseases
Neutrophil elastase is responsible for the blistering in bullous pemphigoidPemphigoid
Pemphigoid is a group of uncommon and rare autoimmune blistering skin diseases. As its name indicates, pemphigoid is similar to pemphigus, but, unlike pemphigus, pemphigoid does not feature acantholysis....
, a skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
condition, in the presence of antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
.
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 immunoglobulineAntibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
A and G (IgA
IGA
Iga or IGA may stand for:-Given name:* a female given name of Polish origin. The name originates from the female given name Jadwiga and stands for gia,or gina in the USA....
, IgG), and cleave both C3bi, a component of the complement system
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
, and CR1, a receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
on neutrophils for another complement molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
involved in phagocytosis. The cleavage of IgA, IgG, C3bi, and CR1 contributes to a decrease of the ability of neutrophils to kill bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
by phagocytosis. Together, all these factors contribute to human pathology
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
.