World Library  
Flag as Inappropriate
Email this Article

Carboxypeptidase E

Article Id: WHEBN0010939045
Reproduction Date:

Title: Carboxypeptidase E  
Author: World Heritage Encyclopedia
Language: English
Subject: Carboxypeptidase A, Proteases, Carboxypeptidase A6, Carboxypeptidase B, Glutamate carboxypeptidase II
Collection:
Publisher: World Heritage Encyclopedia
Publication
Date:
 

Carboxypeptidase E

Carboxypeptidase E
Identifiers
Symbol
External IDs GeneCards:
EC number
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Carboxypeptidase E (CPE), also known as carboxypeptidase H (CPH) and convertase, is an enzyme that in humans is encoded by the CPE gene[1] This enzyme catalyzes the release of C-terminal arginine or lysine residues from polypeptides.

CPE is involved in the biosynthesis of most neuropeptides and peptide hormones.[2] The production of neuropeptides and peptide hormones typically requires two sets of enzymes that cleave the peptide precursors, which are small proteins. First, proprotein convertases cut the precursor at specific sites to generate intermediates containing C-terminal basic residues (lysine and/or arginine). These intermediates are then cleaved by CPE to remove the basic residues. For some peptides, additional processing steps, such as C-terminal amidation, are subsequently required to generate the bioactive peptide, although for many peptides the action of the proprotein convertases and CPE is sufficient to produce the bioactive peptide.[3]

Tissue distribution

Carboxypeptidase E is found in brain and throughout the neuroendocrine system, including the endocrine pancreas, pituitary, and adrenal gland chromaffin cells. Within cells, carboxypeptidase E is present in the secretory granules along with its peptide substrates and products. Carboxypeptidase E is a glycoprotein that exists in both membrane-associated and soluble forms. The membrane-binding is due to an amphiphilic α-helix within the C-terminal region of the protein.

Species distribution

Carboxypeptidase E is found in all species of vertebrates that have been examined, and is also present in many other organisms that have been studied (nematode, sea slug). Carboxypeptidase E is not found in the fruit fly (Drosophila), and another enzyme (presumably carboxypeptidase D) fills in for carboxypeptidase E in this organism. In humans, CPE is encoded by the CPE gene.[1][4]

Function

Carboxypeptidase E
Identifiers
EC number 3.4.17.10
CAS number 81876-95-1
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

Carboxypeptidase E functions in the production of nearly all neuropeptides and peptide hormones. The enzyme acts as an exopeptidase to activate neuropeptides. It does that by cleaving off basic C-terminal amino acids, producing the active form of the peptide. Products of carboxypeptidase E include insulin, the enkephalins, vasopressin, oxytocin, and most other neuroendocrine peptide hormones and neuropeptides.

It has been proposed that membrane-associated carboxypeptidase E acts as a sorting signal for regulated secretory proteins in the trans-Golgi network of the pituitary and in secretory granules; regulated secretory proteins are mostly hormones and neuropeptides.[5] However, this role for carboxypeptidase E remains controversial, and evidence shows that this enzyme is not necessary for the sorting of regulated secretory proteins.

Clinical significance

Mice with mutant carboxypeptidase E, Cpefat, display endocrine disorders like obesity and infertility.[6] In some strains of mice, the fat mutation also causes hyperproinsulinemia in adult male mice, but this is not found in all strains of mice. The obesity and infertility in the Cpefat mice develop with age; young mice (<8 weeks of age) are fertile and have normal body weight. Peptide processing in Cpefat mice is impaired, with a large accumulation of peptides with C-terminal lysine and/or arginine extensions. Levels of the mature forms of peptides are generally reduced in these mice, but not completely eliminated. It is thought that a related enzyme (carboxypeptidase D) also contributes to neuropeptide processing and gives rise to the mature peptides in the Cpefat mice.

In obesity, high levels of circulating free fatty acids have been reported to cause a decrease in the amount of carboxypeptidase E protein in pancreatic beta-cells, leading to beta-cell dysfunction (hyperproinsulinemia) and increased beta-cell apoptosis (via an increase in ER-stress).[7] However, because CPE is not a rate-limiting enzyme for the production of most neuropeptides and peptide hormones, it is not clear how relatively modest decreases in CPE activity can cause physiological effects.

See also

References

  1. ^ a b "Entrez Gene: CPE carboxypeptidase E". 
  2. ^ Fricker LD (1988). "Carboxypeptidase E". Annu. Rev. Physiol. 50: 309–21.  
  3. ^ Fricker LD (2012). "Chapter 3.5 Carboxypeptidase E". Neuropeptides and Other Bioactive Peptides: From Discovery to Function (Color Version). Morgan & Claypool Life Sciences.  
  4. ^ Manser E, Fernandez D, Loo L, Goh PY, Monfries C, Hall C, Lim L (Jun 1990). "Human carboxypeptidase E. Isolation and characterization of the cDNA, sequence conservation, expression and processing in vitro". Biochem J 267 (2): 517–25.  
  5. ^ Cool DR, Normant E, Shen F, et al. (1997). "Carboxypeptidase E is a regulated secretory pathway sorting receptor: genetic obliteration leads to endocrine disorders in Cpe(fat) mice". Cell 88 (1): 73–83.  
  6. ^ Naggert JK, Fricker LD, Varlamov O, et al. (1995). "Hyperproinsulinaemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity". Nat. Genet. 10 (2): 135–42.  
  7. ^ Jeffrey KD, Alejandro EU, Luciani DS, Kalynyak TB, Hu X, Li H, Lin Y, Townsend RR, Polonsky KS, Johnson JD (June 2008). "Carboxypeptidase E mediates palmitate-induced beta-cell ER stress and apoptosis". Proc. Natl. Acad. Sci. U.S.A. 105 (24): 8452–7.  

Further reading

External links

This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 


Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.