Pancreatic elastase
Pancreatic elastase | |||||||||
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ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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Pancreatic elastase II | |||||||||
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Identifiers | |||||||||
ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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Pancreatic endopeptidase E | |||||||||
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ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
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Pancreatic elastase is a form of elastase that is produced in the acinar cells of the pancreas, initially produced as an inactive zymogen and later activated in the duodenum by trypsin. Elastases form a subfamily of serine proteases, characterized by a distinctive structure consisting of two beta barrel domains converging at the active site that hydrolyze amides and esters amongst many proteins in addition to elastin, a type of connective tissue that holds organs together. Pancreatic elastase 1 is a serine endopeptidase, a specific type of protease that has the amino acid serine at its active site. Although the recommended name is pancreatic elastase, it can also be referred to as elastase-1, pancreatopeptidase, PE, or serine elastase.
The first
Clinical literature that describes human elastase 1 activity in the pancreas or fecal material is actually referring to chymotrypsin-like elastase family, member 3B (CELA3B).[1]
Structure
Pancreatic elastase is a compact globular protein with a
Inhibitors
Elafin, the skin-derived elastase inhibitor, has been shown to be a potent and specific inhibitor of both the porcine homolog of ELA1 and human leukocyte elastase in vitro. Elafin is expressed by epidermal keratinocytes under hyperproliferative conditions such as psoriasis and wound healing. It has also been reported to be present in many other adult epithelia that are exposed to environmental stimuli: tongue, plate, lingual tonsils, gingiva, pharynx, epiglottis, vocal fold, esophagus, uterine cervix, vagina, and hair follicles. In all these tissues, the presence of inflammatory cells is physiologic and elafin expression is believed to protect against leukocyte proteases, thereby helping to maintain epithelial integrity.[citation needed]
Elafin on the contrary has never been found in the basal layer in any type of epithelial tissue. Indeed, elafin is virtually absent in normal human epidermis. The other known elastase inhibitor, SLPI, however, has been reported to be expressed in the basal keratinocytes suggesting that this may be the major elastase inhibitor in normal epidermis.[citation needed]
Clinical significance
Mutations of the CELA1 gene were suspected to be associated with
A possible
Biosynthesis
Pancreatic elastase is formed by activation of proelastase from mammalian pancreas by trypsin. After processing to proelastase, it is stored in the zymogen granules and then activated to elastase in the duodenum by the tryptic cleavage of a peptide bond in the inactive form of the precursor molecule.[8] This process results in the removal of an activation peptide from the N-terminal, that enables the enzyme to adopt its native conformation.[citation needed]
Isozymes
Humans have five chymotrypsin-like elastase genes which encode the structurally similar proteins:
Family | Gene symbol | Protein name | EC number | ||
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Approved | Previous | Approved | Previous | ||
chymotrypsin- like |
CELA1 | ELA1 | chymotrypsin-like elastase family, member 1 | elastase 1, pancreatic | EC 3.4.21.36 |
CELA2A | ELA2A | chymotrypsin-like elastase family, member 2A | elastase 2A, pancreatic | EC 3.4.21.71 | |
CELA2B | ELA2B | chymotrypsin-like elastase family, member 2B | elastase 2B, pancreatic | EC 3.4.21.71 | |
CELA3A | ELA3A | chymotrypsin-like elastase family, member 3A | elastase 3A, pancreatic | EC 3.4.21.70 | |
CELA3B | ELA3B | chymotrypsin-like elastase family, member 3B | elastase 3B, pancreatic | EC 3.4.21.70 |
Post-translational modifications
Glycosylation at Asn79 and Asn233.[9]
Gene
The gene that codes for pancreatic elastase 1 is CELA1 (synonym: ELA1)
Pancreatic elastase 1 is encoded by a single genetic locus on chromosome 12. Studies of human pancreatic elastase 1 have shown that this serine protease maps to the chromosomal region 12q13
Reactions
The hydrolysis that elastases bring about occur in several steps, starting with the formation of a complex between elastase and its substrate, with the carbonyl carbon positioned near the nucleophilic serine, followed by a nucleophillic attack that forms an acyl-enzyme intermediate (a pair of electrons from the double bond of the carbonyl oxygen moves to the oxygen) while the first product is released. The intermediate is then hydrolyzed in a deacylation step, regenerating the active enzyme and resulting in the release of the second product ( the electron-deficient carbonyl carbon re-forms the double bond with the oxygen and the C-terminus of the peptide is released. It preferentially cleaves peptide bonds at the carbonyl end of amino acid residues with small hydrophobic side chains such as glycine, valine, leucine, isoleucine and alanine. The wide specificity of elastases for non-aromatic uncharged side chains can explain its ability to break down native elastin.[11]
Use in diagnostic tests
Human pancreatic elastase 1 (E1) is not degraded in intestinal transit, so that its concentration in feces reflects exocrine pancreatic function. In inflammation of the pancreas, E1 is released into the bloodstream. Thus the quantification of pancreatic elastase 1 in serum allows diagnosis or exclusion of acute pancreatitis.[12]
Main indications:
- Diagnosis and exclusion of exocrine pancreatic insufficiency caused by, e.g.,
- Follow-up monitoring of patients with mild or moderate pancreatic insufficiency
- Diagnosis and exclusion of pancreatic involvement in, e.g., gastrointestinal symptoms, abdominal pain, osteoporosis.[13]
Method of detection:
- Sandwich ELISA with two monoclonal antibodies highly specific for human pancreatic elastase 1
- The ELISA kit is based on a microtiter plate (96 well format) with 12 breakable single strips x 8 wells suitable for up to 42 samples in duplicate
Reference concentration to interpret Pancreatic Elastase results: For adults and children after the first month of life
- Values > 200 μg elastase/g stool indicate normal exocrine pancreatic function
- Values of 100-200 μg elastase/g stool suggest mild to moderate pancreatic insuffiency
- Values < 100 μg elastase/g stool indicate exocrine pancreatic insufficiency.[14]
References
- ^ a b EntrezGene 1990
- PMID 9175736.
- ^ PMID 10620133.
- ^ Universal protein resource accession number Q9UNI1 at UniProt.
- ^ "Elastase". Worthington Enzyme Manual.
- PMID 819031.
- S2CID 36039184.
- PMID 5461547.
- ^ "CELA1 Gene". GeneCards.
- PMID 8575772.
- ISBN 9780121818814.
- PMID 8761139.
- PMID 21503378.
- PMID 8944569.
External links
- Pancreatic+Elastase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Overview of all the structural information available in the PDB for UniProt: P00772 (Pancreatic elastase) at the PDBe-KB.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.