Names | |
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IUPAC name
L-Tyrosylglycylglycyl-L-phenylalanyl-L-methionyl-L-threonyl-L-seryl-L-glutaminyl-L-lysyl-L-seryl-L-glutaminyl-L-threonyl-L-prolyl-L-leucyl-L-valyl-L-threonyl-L-leucyl-L-phenylalanyl-L-lysyl-L-asparaginyl-L-alanyl-L-isoleucyl-L-isoleucyl-L-lysyl-L-asparaginyl-L-alanyl-L-tyrosyl-L-lysyl-L-lysylglycyl-L-glutamine
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Identifiers | |
3D model (
JSmol)
|
|
ChEBI | |
ChemSpider | |
ECHA InfoCard | 100.056.646 |
PubChem
CID
|
|
UNII | |
| |
| |
Properties | |
C158H251N39O46S | |
Molar mass | 3465.03 g·mol−1 |
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
|
β-Endorphin (beta-endorphin) is an endogenous opioid neuropeptide and peptide hormone that is produced in certain neurons within the central nervous system and peripheral nervous system. [1] It is one of three endorphins that are produced in humans, the others of which include α-endorphin and γ-endorphin. [2]
There are multiple forms of β-endorphins with the full sequence of Tyr- Gly-Gly- Phe- Met- Thr- Ser- Glu- Lys-Ser- Gln-Thr- Pro- Leu- Val-Thr-Leu-Phe-Lys- Asn- Ala- Ile-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-Glu (31 amino acids) denoted as β-endorphin(1-31) and variants truncated to the first 26 and 27 amino acids as β-endorphin(1-26) and β-endorphin(1-27). [1] [3] [4] The first 16 amino acids are identical to α-endorphin. β-Endorphin is considered to be a part of the endogenous opioid and endorphin classes of neuropeptides; [1] all of the established endogenous opioid peptides contain the same N-terminal amino acid sequence, Tyr-Gly-Gly-Phe, followed by either -Met or -Leu. [1]
Function of β-endorphin has been known to be associated with hunger, thrill, pain, maternal care, sexual behavior, and reward cognition. In the broadest sense, β-endorphin is primarily utilized in the body to reduce stress and maintain homeostasis. In behavioral research, studies have shown that β-endorphin is released via volume transmission into the ventricular system in response to a variety of stimuli, and novel stimuli in particular. [5]
β-Endorphin is found in neurons of the hypothalamus, as well as the pituitary gland. It is derived from β-lipotropin, which is produced in the pituitary gland from a larger peptide precursor, proopiomelanocortin (POMC). [6] POMC is cleaved into two neuropeptides, adrenocorticotropic hormone (ACTH) and β-lipotropin. [7] The formation of β-endorphin is then the result of cleavage of the C-terminal region of β-lipotropin, producing a 31 amino acid-long neuropeptide with an alpha-helical secondary structure. However, POMC also gives rise to other peptide hormones, including α- and γ- melanocyte-stimulating hormone (MSH), resulting from intracellular processing by internal enzymes known as prohormone convertases.
A significant factor that differentiates β-endorphin from other endogenous opioids is its high affinity for and lasting effect on μ-opioid receptors. [6] The structure of β-endorphin in part accounts for this through its resistance to proteolytic enzymes, as its secondary structure makes it less vulnerable to degradation. [6]
β-Endorphin function is said to be divided into two main categories: local function and global function. Global function of β-endorphin is related to decreasing bodily stress and maintaining homeostasis resulting in pain management, reward effects, and behavioral stability. β-Endorphin in global pathways diffuse to different parts of the body through cerebral spinal fluid in the spinal cord, allowing for β-endorphin release to affect the peripheral nervous system. Localized function of β-endorphin results in release of β-endorphin in different brain regions such as the amygdala or the hypothalamus. [5] The two main methods by which β-endorphin is utilized in the body are peripheral hormonal action [8] and neuroregulation. β-endorphin and other enkephalins are often released with ACTH to modulate hormone system functioning. Neuroregulation by β-endorphin occurs through interference with the function of another neuropeptide, either by direct inhibition of neuropeptide release or induction of a signaling cascade that reduces a neuropeptide's effects. [7]
β-Endorphin is an agonist of the opioid receptors; it preferentially binds to the μ-opioid receptor. [1] Evidence suggests that it serves as a primary endogenous ligand for the μ-opioid receptor, [1] [9] the same receptor to which the chemicals extracted from opium, such as morphine, derive their analgesic properties. β-Endorphin has the highest binding affinity of any endogenous opioid for the μ-opioid receptor. [1] [6] [9] Opioid receptors are a class of G-protein coupled receptors, such that when β-endorphin or another opioid binds, a signaling cascade is induced in the cell. [10] Acetylation of the N-terminus of β-endorphin, however, inactivates the neuropeptide, preventing it from binding to its receptor. [6] The opioid receptors are distributed throughout the central nervous system and within the peripheral tissue of neural and non-neural origin. They are also located in high concentrations in the Periaqueductal gray, Locus coeruleus, and the Rostral ventromedial medulla. [11]
Voltage-dependent calcium channels (VDCCs) are important membrane proteins that mediate the depolarization of neurons, and play a major role in promoting the release of neurotransmitters. When endorphin molecules bind to opioid receptors, G proteins activate and dissociate into their constituent Gα and Gβγ sub-units. The Gβγ sub-unit binds to the intracellular loop between the two trans-membrane helices of the VDCC. When the sub-unit binds to the voltage-dependent calcium channel, it produces a voltage-dependent block, which inhibits the channel, preventing the flow of calcium ions into the neuron. Embedded in the cell membrane is also the G protein-coupled inwardly-rectifying potassium channel. When a Gβγ or Gα(GTP) molecule binds to the C-terminus of the potassium channel, it becomes active, and potassium ions are pumped out of the neuron. [12] [13] The activation of the potassium channel and subsequent deactivation of the calcium channel causes membrane hyperpolarization. This is when there is a change in the membrane's potential, so that it becomes more negative. The reduction in calcium ions causes a reduction of neurotransmitter release because calcium is essential for this event to occur. [14] This means that neurotransmitters such as glutamate and substance P cannot be released from the presynaptic terminal of the neurons. These neurotransmitters are vital in the transmission of pain, and as β-Endorphin reduces the release of these substances, there is a strong analgesic effect.
β-Endorphin has been primarily studied for its influence on nociception (i.e., pain perception). β-endorphin modulates pain perception both in the central nervous system and the peripheral nervous system. When pain is perceived, pain receptors ( nociceptors) send signals to the dorsal horn of the spinal cord and then up to the hypothalamus through the release of a neuropeptide called substance P. [7] [5] [15] [16] In the peripheral nervous system, this signal causes the recruitment of T-lymphocytes, white blood cells of the immune system, to the area where pain was perceived. [16] T-lymphocytes release β-endorphin in this localized region, allowing it to bind to opioid receptors, causing direct inhibition of substance P. [16] [17] In the central nervous system, β-endorphin binds to opioid receptors in the dorsal root and inhibits the release of substance P in the spinal cord, reducing the number of excitatory pain signals sent to the brain. [16] [15] The hypothalamus responds to the pain signal by releasing β-endorphin through the periaqueductal grey network, which mainly acts to inhibit the release of GABA, a neurotransmitter which prevents the release of dopamine. [7] [15] Thus, the inhibition of GABA release by β-endorphin allows for a greater release of dopamine, in part contributing to the analgesic effect of β-endorphin. [7] [15] The combination of these pathways reduces pain sensation, allowing for the body to stop a pain impulse once it has been sent.
β-Endorphin has approximately 18 to 33 times the analgesic potency of morphine, [18] though its hormonal effect is species dependent. [8]
β-Endorphin release in response to exercise has been known and studied since at least the 1980s. [19] Studies have demonstrated that serum concentrations of endogenous opioids, in particular β-endorphin and β-lipotropin, increase in response to both acute exercise and training. [19] The release of β-endorphin during exercise is associated with a phenomenon colloquially known in popular culture as a runner's high. [20]
There is evidence that β-endorphin is released in response to ultraviolet radiation, either through sun exposure or artificial tanning. [21] This is thought to contribute to addiction behavior among excessive sunbathers and users of artificial tanning despite health risks.
β-Endorphin acts as an agonist that binds to various types of G protein–coupled receptors(GPCRs), most notably to the mu, delta, and kappa opioid receptors. The receptors are responsible for supra-spinal analgesia.[ medical citation needed]
β-Endorphin was discovered in camel pituitary extracts by C.H. Li and David Chung. [22] The primary structure of β-endorphin was unknowingly determined 10 years earlier, when Li and colleagues analyzed the sequence of another neuropeptide produced in the pituitary gland, γ-lipotropin. They noticed that the C-terminus region of this neuropeptide was similar to that of some enkephalins, suggesting that it may have a similar function to these neuropeptides. The C-terminal sequence of γ-lipotropin turned out to be the primary sequence of the β-endorphin. [6]
Opioid Peptides
β-Endorphin (also a pituitary hormone) ...
Opioid peptides are encoded by three distinct genes. These precursors include POMC, from which the opioid peptide β-endorphin and several nonopioid peptides are derived, as discussed earlier; proenkephalin, from which met-enkephalin and leu-enkephalin are derived; and prodynorphin, which is the precursor of dynorphin and related peptides. Although they come from different precursors, opioid peptides share significant amino acid sequence identity. Specifically, all of the well-validated endogenous opioids contain the same four N-terminal amino acids (Tyr-Gly-Gly-Phe), followed by either Met or Leu ... Among endogenous opioid peptides, β-endorphin binds preferentially to μ receptors. ... Shared opioid peptide sequences. Although they vary in length from as few as five amino acids (enkephalins) to as many as 31 (β-endorphin), the endogenous opioid peptides shown here contain a shared N-terminal sequence followed by either Met or Leu.
Principal endogenous agonists (Human)
β-endorphin (POMC, P01189), [Met]enkephalin (PENK, P01210), [Leu]enkephalin (PENK, P01210) ...
Comments: β-Endorphin is the highest potency endogenous ligand
Names | |
---|---|
IUPAC name
L-Tyrosylglycylglycyl-L-phenylalanyl-L-methionyl-L-threonyl-L-seryl-L-glutaminyl-L-lysyl-L-seryl-L-glutaminyl-L-threonyl-L-prolyl-L-leucyl-L-valyl-L-threonyl-L-leucyl-L-phenylalanyl-L-lysyl-L-asparaginyl-L-alanyl-L-isoleucyl-L-isoleucyl-L-lysyl-L-asparaginyl-L-alanyl-L-tyrosyl-L-lysyl-L-lysylglycyl-L-glutamine
| |
Identifiers | |
3D model (
JSmol)
|
|
ChEBI | |
ChemSpider | |
ECHA InfoCard | 100.056.646 |
PubChem
CID
|
|
UNII | |
| |
| |
Properties | |
C158H251N39O46S | |
Molar mass | 3465.03 g·mol−1 |
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
|
β-Endorphin (beta-endorphin) is an endogenous opioid neuropeptide and peptide hormone that is produced in certain neurons within the central nervous system and peripheral nervous system. [1] It is one of three endorphins that are produced in humans, the others of which include α-endorphin and γ-endorphin. [2]
There are multiple forms of β-endorphins with the full sequence of Tyr- Gly-Gly- Phe- Met- Thr- Ser- Glu- Lys-Ser- Gln-Thr- Pro- Leu- Val-Thr-Leu-Phe-Lys- Asn- Ala- Ile-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-Glu (31 amino acids) denoted as β-endorphin(1-31) and variants truncated to the first 26 and 27 amino acids as β-endorphin(1-26) and β-endorphin(1-27). [1] [3] [4] The first 16 amino acids are identical to α-endorphin. β-Endorphin is considered to be a part of the endogenous opioid and endorphin classes of neuropeptides; [1] all of the established endogenous opioid peptides contain the same N-terminal amino acid sequence, Tyr-Gly-Gly-Phe, followed by either -Met or -Leu. [1]
Function of β-endorphin has been known to be associated with hunger, thrill, pain, maternal care, sexual behavior, and reward cognition. In the broadest sense, β-endorphin is primarily utilized in the body to reduce stress and maintain homeostasis. In behavioral research, studies have shown that β-endorphin is released via volume transmission into the ventricular system in response to a variety of stimuli, and novel stimuli in particular. [5]
β-Endorphin is found in neurons of the hypothalamus, as well as the pituitary gland. It is derived from β-lipotropin, which is produced in the pituitary gland from a larger peptide precursor, proopiomelanocortin (POMC). [6] POMC is cleaved into two neuropeptides, adrenocorticotropic hormone (ACTH) and β-lipotropin. [7] The formation of β-endorphin is then the result of cleavage of the C-terminal region of β-lipotropin, producing a 31 amino acid-long neuropeptide with an alpha-helical secondary structure. However, POMC also gives rise to other peptide hormones, including α- and γ- melanocyte-stimulating hormone (MSH), resulting from intracellular processing by internal enzymes known as prohormone convertases.
A significant factor that differentiates β-endorphin from other endogenous opioids is its high affinity for and lasting effect on μ-opioid receptors. [6] The structure of β-endorphin in part accounts for this through its resistance to proteolytic enzymes, as its secondary structure makes it less vulnerable to degradation. [6]
β-Endorphin function is said to be divided into two main categories: local function and global function. Global function of β-endorphin is related to decreasing bodily stress and maintaining homeostasis resulting in pain management, reward effects, and behavioral stability. β-Endorphin in global pathways diffuse to different parts of the body through cerebral spinal fluid in the spinal cord, allowing for β-endorphin release to affect the peripheral nervous system. Localized function of β-endorphin results in release of β-endorphin in different brain regions such as the amygdala or the hypothalamus. [5] The two main methods by which β-endorphin is utilized in the body are peripheral hormonal action [8] and neuroregulation. β-endorphin and other enkephalins are often released with ACTH to modulate hormone system functioning. Neuroregulation by β-endorphin occurs through interference with the function of another neuropeptide, either by direct inhibition of neuropeptide release or induction of a signaling cascade that reduces a neuropeptide's effects. [7]
β-Endorphin is an agonist of the opioid receptors; it preferentially binds to the μ-opioid receptor. [1] Evidence suggests that it serves as a primary endogenous ligand for the μ-opioid receptor, [1] [9] the same receptor to which the chemicals extracted from opium, such as morphine, derive their analgesic properties. β-Endorphin has the highest binding affinity of any endogenous opioid for the μ-opioid receptor. [1] [6] [9] Opioid receptors are a class of G-protein coupled receptors, such that when β-endorphin or another opioid binds, a signaling cascade is induced in the cell. [10] Acetylation of the N-terminus of β-endorphin, however, inactivates the neuropeptide, preventing it from binding to its receptor. [6] The opioid receptors are distributed throughout the central nervous system and within the peripheral tissue of neural and non-neural origin. They are also located in high concentrations in the Periaqueductal gray, Locus coeruleus, and the Rostral ventromedial medulla. [11]
Voltage-dependent calcium channels (VDCCs) are important membrane proteins that mediate the depolarization of neurons, and play a major role in promoting the release of neurotransmitters. When endorphin molecules bind to opioid receptors, G proteins activate and dissociate into their constituent Gα and Gβγ sub-units. The Gβγ sub-unit binds to the intracellular loop between the two trans-membrane helices of the VDCC. When the sub-unit binds to the voltage-dependent calcium channel, it produces a voltage-dependent block, which inhibits the channel, preventing the flow of calcium ions into the neuron. Embedded in the cell membrane is also the G protein-coupled inwardly-rectifying potassium channel. When a Gβγ or Gα(GTP) molecule binds to the C-terminus of the potassium channel, it becomes active, and potassium ions are pumped out of the neuron. [12] [13] The activation of the potassium channel and subsequent deactivation of the calcium channel causes membrane hyperpolarization. This is when there is a change in the membrane's potential, so that it becomes more negative. The reduction in calcium ions causes a reduction of neurotransmitter release because calcium is essential for this event to occur. [14] This means that neurotransmitters such as glutamate and substance P cannot be released from the presynaptic terminal of the neurons. These neurotransmitters are vital in the transmission of pain, and as β-Endorphin reduces the release of these substances, there is a strong analgesic effect.
β-Endorphin has been primarily studied for its influence on nociception (i.e., pain perception). β-endorphin modulates pain perception both in the central nervous system and the peripheral nervous system. When pain is perceived, pain receptors ( nociceptors) send signals to the dorsal horn of the spinal cord and then up to the hypothalamus through the release of a neuropeptide called substance P. [7] [5] [15] [16] In the peripheral nervous system, this signal causes the recruitment of T-lymphocytes, white blood cells of the immune system, to the area where pain was perceived. [16] T-lymphocytes release β-endorphin in this localized region, allowing it to bind to opioid receptors, causing direct inhibition of substance P. [16] [17] In the central nervous system, β-endorphin binds to opioid receptors in the dorsal root and inhibits the release of substance P in the spinal cord, reducing the number of excitatory pain signals sent to the brain. [16] [15] The hypothalamus responds to the pain signal by releasing β-endorphin through the periaqueductal grey network, which mainly acts to inhibit the release of GABA, a neurotransmitter which prevents the release of dopamine. [7] [15] Thus, the inhibition of GABA release by β-endorphin allows for a greater release of dopamine, in part contributing to the analgesic effect of β-endorphin. [7] [15] The combination of these pathways reduces pain sensation, allowing for the body to stop a pain impulse once it has been sent.
β-Endorphin has approximately 18 to 33 times the analgesic potency of morphine, [18] though its hormonal effect is species dependent. [8]
β-Endorphin release in response to exercise has been known and studied since at least the 1980s. [19] Studies have demonstrated that serum concentrations of endogenous opioids, in particular β-endorphin and β-lipotropin, increase in response to both acute exercise and training. [19] The release of β-endorphin during exercise is associated with a phenomenon colloquially known in popular culture as a runner's high. [20]
There is evidence that β-endorphin is released in response to ultraviolet radiation, either through sun exposure or artificial tanning. [21] This is thought to contribute to addiction behavior among excessive sunbathers and users of artificial tanning despite health risks.
β-Endorphin acts as an agonist that binds to various types of G protein–coupled receptors(GPCRs), most notably to the mu, delta, and kappa opioid receptors. The receptors are responsible for supra-spinal analgesia.[ medical citation needed]
β-Endorphin was discovered in camel pituitary extracts by C.H. Li and David Chung. [22] The primary structure of β-endorphin was unknowingly determined 10 years earlier, when Li and colleagues analyzed the sequence of another neuropeptide produced in the pituitary gland, γ-lipotropin. They noticed that the C-terminus region of this neuropeptide was similar to that of some enkephalins, suggesting that it may have a similar function to these neuropeptides. The C-terminal sequence of γ-lipotropin turned out to be the primary sequence of the β-endorphin. [6]
Opioid Peptides
β-Endorphin (also a pituitary hormone) ...
Opioid peptides are encoded by three distinct genes. These precursors include POMC, from which the opioid peptide β-endorphin and several nonopioid peptides are derived, as discussed earlier; proenkephalin, from which met-enkephalin and leu-enkephalin are derived; and prodynorphin, which is the precursor of dynorphin and related peptides. Although they come from different precursors, opioid peptides share significant amino acid sequence identity. Specifically, all of the well-validated endogenous opioids contain the same four N-terminal amino acids (Tyr-Gly-Gly-Phe), followed by either Met or Leu ... Among endogenous opioid peptides, β-endorphin binds preferentially to μ receptors. ... Shared opioid peptide sequences. Although they vary in length from as few as five amino acids (enkephalins) to as many as 31 (β-endorphin), the endogenous opioid peptides shown here contain a shared N-terminal sequence followed by either Met or Leu.
Principal endogenous agonists (Human)
β-endorphin (POMC, P01189), [Met]enkephalin (PENK, P01210), [Leu]enkephalin (PENK, P01210) ...
Comments: β-Endorphin is the highest potency endogenous ligand