Carboxypeptidase E
Encyclopedia
Carboxypeptidase E, also known as carboxypeptidase H and enkephalin convertase, is an enzyme
that in humans is encoded by the CPE gene
.
Carboxypeptidase E is found in brain and throughout the neuroendocrine system, including the endocrine pancreas, pituitary, and adrenal gland
chromaffin cell
s. 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. 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.
Carboxypeptidase E functions in the production of nearly all neuropeptides and peptide hormones. The enzyme acts as an exopeptidase
to activate neuropeptide
s. It does that by cleaving off basic C-terminal amino acids, producing the active form of the peptide. Products of carboxypeptidase E include insulin, enkephalin, 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 hormone
s and neuropeptide
s. However, this role for carboxypeptidase E remains controversial, and evidence shows that this enzyme is not necessary for the sorting of regulated secretory proteins.
Mice with mutant carboxypeptidase E, Cpefat, display endocrine disorders like obesity
and infertility
. 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.
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...
that in humans is encoded by the CPE gene
Gene
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...
.
Carboxypeptidase E is found in brain and throughout the neuroendocrine system, including the endocrine pancreas, pituitary, and adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
chromaffin cell
Chromaffin cell
Chromaffin cells are neuroendocrine cells found in the medulla of the adrenal gland and in other ganglia of the sympathetic nervous system. They are modified post-synaptic sympathetic neurons that receive sympathetic input...
s. Within cells, carboxypeptidase E is present in the secretory granules along with its peptide substrates and products. Carboxypeptidase E is a glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
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. 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.
Carboxypeptidase E functions in the production of nearly all neuropeptides and peptide hormones. The enzyme acts as an exopeptidase
Exopeptidase
An exopeptidase is an enzyme produced in the pancreas that catalyses the removal of an amino acid from the end of a polypeptide chain. Exopeptidase cleaves the end of a polypeptide chain....
to activate neuropeptide
Neuropeptide
Neuropeptides are small protein-like molecules used by neurons to communicate with each other. They are neuronal signaling molecules, influence the activity of the brain in specific ways and are thus involved in particular brain functions, like analgesia, reward, food intake, learning and...
s. It does that by cleaving off basic C-terminal amino acids, producing the active form of the peptide. Products of carboxypeptidase E include insulin, enkephalin, 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
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
of the pituitary and in secretory granules; regulated secretory proteins are mostly hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s and neuropeptide
Neuropeptide
Neuropeptides are small protein-like molecules used by neurons to communicate with each other. They are neuronal signaling molecules, influence the activity of the brain in specific ways and are thus involved in particular brain functions, like analgesia, reward, food intake, learning and...
s. However, this role for carboxypeptidase E remains controversial, and evidence shows that this enzyme is not necessary for the sorting of regulated secretory proteins.
Mice with mutant carboxypeptidase E, Cpefat, display endocrine disorders like obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
and infertility
Infertility
Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
. In some strains of mice, the fat mutation also causes hyperproinsulinemia
Hyperproinsulinemia
Hyperproinsulinemia is a disease where insulin is not sufficiently processed before secretion and immature forms of insulin make up the majority of circulating insulin immunoreactivity in both fasting and glucose-stimulated conditions...
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.
External links
- The MEROPSMeropsMerops may refer to:* Merops , a genus of bee-eaters.* MEROPS, an on-line database for peptidases.It may also refer to several figures from Greek mythology:* King of Ethiopia, husband of Clymene, who lay with Helios and bore Phaethon...
online database for peptidases and their inhibitors: M14.005