Enkephaline
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An enkephalin is a pentapeptide involved in regulating
nociception Nociception (also nocioception, from Latin ''nocere'' 'to harm or hurt') is the sensory nervous system's process of encoding noxious stimuli. It deals with a series of events and processes required for an organism to receive a painful stimulus, co ...
in the body. The enkephalins are termed endogenous
ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...
s, as they are internally derived and bind to the body's
opioid receptors Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin r ...
. Discovered in 1975, two forms of enkephalin have been found, one containing leucine ("leu"), and the other containing
methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...
("met"). Both are products of the proenkephalin
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
. *
Met-enkephalin Met-enkephalin, also known as metenkefalin (INN), sometimes referred to as opioid growth factor (OGF), is a naturally occurring, endogenous opioid peptide that has opioid effects of a relatively short duration. It is one of the two forms of enkep ...
is Tyr-Gly-Gly-Phe-Met. *
Leu-enkephalin Leu-enkephalin is an endogenous opioid peptide neurotransmitter with the amino acid sequence Tyr-Gly-Gly-Phe-Leu that is found naturally in the brains of many animals, including humans. It is one of the two forms of enkephalin; the other is met-e ...
has Tyr-Gly-Gly-Phe-Leu.


Endogenous opioid peptides

There are three well-characterized families of opioid peptides produced by the body: enkephalins,
B-endorphin ''beta''-Endorphin (β-endorphin) is an endogenous opioid neuropeptide and peptide hormone that is produced in certain neurons within the central nervous system and peripheral nervous system. It is one of three endorphins that are produced in ...
, and dynorphins. The met-enkephalin peptide sequence is coded for by the enkephalin gene; the leu-enkephalin peptide sequence is coded for by both the enkephalin gene and the dynorphin gene. The proopiomelanocortin gene ( POMC) also contains the met-enkephalin sequence on the N-terminus of beta-endorphin, but the endorphin peptide is not processed into enkephalin.


Effects on stress

Enkephalin is also considered a
neuropeptide Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the ...
, which in the human body performs as an important signaling molecule in the brain. Enkephalins are found in high concentration in the
brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
as well as in the cells of
adrenal medulla The adrenal medulla ( la, medulla glandulae suprarenalis) is part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of chromaffin cel ...
. In response to pain,
norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
, a
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
that is activated in fight-or-flight response is released, along with
endorphins Endorphins (contracted from endogenous morphine) are chemical signals in the brain that block the perception of pain and increase feelings of wellbeing. They are produced and stored in an area of the brain known as the pituitary gland. Hist ...
. A 2017 study indicates that this polypeptide may be linked to brain functioning during the stress response, especially in the
hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
and
prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46, ...
. This research has suggested that, as part of the stress response, several met-enkephalin analogs have increased activity in the
hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
, while leu-enkephalin analogs as well as somatostatins are
downregulated In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary proce ...
during stress. Stressors may impact neuropeptides whose action is localized to a specific brain region.


Enkephalin receptor

The receptors for enkephalin are the
delta opioid receptor Delta commonly refers to: * Delta (letter) (Δ or δ), a letter of the Greek alphabet * River delta, at a river mouth * D (NATO phonetic alphabet: "Delta") * Delta Air Lines, US * Delta variant of SARS-CoV-2 that causes COVID-19 Delta may also r ...
s and mu opioid receptors. Opioid receptors are a group of G-protein-coupled receptors, with other
opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
s as
ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...
s as well. The other
endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...
opioids Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...
are dynorphins (that bind to kappa receptors),
endorphin Endorphins (contracted from endogenous morphine) are chemical signals in the brain that block the perception of pain and increase feelings of wellbeing. They are produced and stored in an area of the brain known as the pituitary gland. Hist ...
s (mu receptors), endomorphins, and nociceptin/orphanin FQ. The opioid receptors are ~40% identical to
somatostatin Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-couple ...
receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
s (SSTRs).


See also

*
Endorphin Endorphins (contracted from endogenous morphine) are chemical signals in the brain that block the perception of pain and increase feelings of wellbeing. They are produced and stored in an area of the brain known as the pituitary gland. Hist ...
*
Enkephalinase Enkephalinases are enzymes that degrade endogenous enkephalin opioid peptides. They include: * Aminopeptidase N (APN) * Neutral endopeptidase (NEP) * Dipeptidyl peptidase 3 (DPP3) * Carboxypeptidase A6 (CPA6) * Leucyl/cystinyl aminopeptidase ( ...
*
Opioid peptide Opioid peptides are peptides that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Such peptides may be produced by the body itself, for example endorphins. The effects of these peptides vary, but th ...
* Racecadotril * RB-101


References


External links

* * Opioid peptides Pentapeptides {{biochemistry-stub