Correlación estructural entre las encefalinas y la morfina

Opioid peptides are

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

s that bind to

opioid receptor 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 somatosta ...

s in the brain;

opiate An opiate, in classical pharmacology, is a substance derived from opium. In more modern usage, the term ''opioid'' is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain (including antagonist ...

s and

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 opioi ...

s mimic the effect of these peptides. Such peptides may be produced by the body itself, for example

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. The effects of these peptides vary, but they all resemble those of opiates. Brain opioid peptide systems are known to play an important role in

motivation Motivation is the reason for which humans and other animals initiate, continue, or terminate a behavior at a given time. Motivational states are commonly understood as forces acting within the agent that create a disposition to engage in goal-dire ...

emotion Emotions are mental states brought on by neurophysiological changes, variously associated with thoughts, feelings, behavioral responses, and a degree of pleasure or displeasure. There is currently no scientific consensus on a definition. ...

, attachment behaviour, the response to stress and

pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

, control of food intake, and the rewarding effects of

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

and nicotine. Opioid-like peptides may also be absorbed from partially

digested Digestion is the breakdown of large insoluble food molecules into small water-soluble food molecules so that they can be absorbed into the watery blood plasma. In certain organisms, these smaller substances are absorbed through the small inte ...

food Food is any substance consumed by an organism for nutritional support. Food is usually of plant, animal, or fungal origin, and contains essential nutrients, such as carbohydrates, fats, proteins, vitamins, or minerals. The substance is ...

(

casomorphin Casomorphin is an opioid peptide (protein fragment) derived from the digestion of the milk protein casein. Health Digestive enzymes can break casein down into peptides that have some biological activity in cells and in laboratory animals though ...

s, exorphins, and

rubiscolin The rubiscolins are a group of opioid peptides that are formed during digestion of the ribulose bisphosphate carboxylase/oxygenase (Rubisco) protein from spinach leaves. These peptides have much in common with the better-known gluten exorphin Glut ...

s). The

opioid food peptides Opioid food peptides include: * Casomorphin (from milk) * Gluten exorphin (from gluten) * Gliadorphin/gluteomorphin (from gluten) * Rubiscolin (from spinach) * Soymorphin-5 (from soy) * Oryzatensin (from rice Rice is the seed of the gr ...

have lengths of typically 4–8

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

s. The body's own opioids are generally much longer. Opioid peptides are released by post-translational

proteolytic cleavage Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases ...

precursor protein A protein precursor, also called a pro-protein or pro-peptide, is an inactive protein (or peptide) that can be turned into an active form by post-translational modification, such as breaking off a piece of the molecule or adding on another molecule ...

s. The precursors consist of the following components: a signal sequence that precedes a conserved region of about 50 residues; a variable-length region; and the sequence of the

neuropeptides 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 ...

themselves.

Sequence In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is called ...

analysis reveals that the conserved

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

region of the precursors contains 6

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, s ...

s, which are probably involved in

disulfide bond In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups ...

formation. It is speculated that this region might be important for neuropeptide processing.

Endogenous

The human

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ...

contains several

homologous Homology may refer to: Sciences Biology *Homology (biology), any characteristic of biological organisms that is derived from a common ancestor *Sequence homology, biological homology between DNA, RNA, or protein sequences * Homologous chrom ...

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 b ...

s that are known to code for endogenous opioid peptides. *The nucleotide sequence of the human gene for

proopiomelanocortin Pro-opiomelanocortin (POMC) is a precursor polypeptide with 241 amino acid residues. POMC is synthesized in corticotrophs of the anterior pituitary from the 267-amino-acid-long polypeptide precursor pre-pro-opiomelanocortin (pre-POMC), by the r ...

(POMC) was characterized in 1980. The POMC gene codes for endogenous opioids such as

β-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

γ-endorphin γ-Endorphin (''gamma''-endorphin) is an opioid peptide that is characterized by the presence of 17 amino acids. The first 16 amino acids are identical to α-endorphin; leucine added at the end. In addition, γ-endorphin is identical to the firs ...

. *The human gene for the

enkephalin An enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, as they are internally derived and bind to the body's opioid receptors. Discovered in 1975, two forms of enkephalin ...

s was isolated and its sequence described in 1982. *The human gene for

dynorphin Dynorphins (Dyn) are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 (PC2), multiple active peptides are released: dynorphin A, dynorphin ...

s (originally called the "Enkephalin B" gene because of sequence similarity to the enkephalin gene) was isolated and its sequence described in 1983. *The PNOC gene encoding prepronociceptin, which is cleaved into

nociceptin Nociceptin/orphanin FQ (N/OFQ), a 17-amino acid neuropeptide, is the endogenous ligand for the nociceptin receptor (NOP, ORL-1). Nociceptin acts as a potent anti-analgesic, effectively counteracting the effect of pain-relievers; it's activation ...

and potentially two additional neuropeptides. * Adrenorphin, amidorphin, and leumorphin were discovered in the 1980s. *The

endomorphin Endomorphins are considered to be natural opioid neurotransmitters central to pain relief. The two known endomorphins, endomorphin-1 and endomorphin-2, are tetrapeptides, consisting of Tyr-Pro-Trp-Phe and Tyr-Pro-Phe-Phe amino acid sequences re ...

s were discovered in the 1990s. * Opiorphin and spinorphin, enkephalinase inhibitors (i.e., prevent the metabolism of enkephalins). * Hemorphins,

hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...

-derived opioid peptides, including hemorphin-4, valorphin, and spinorphin, among others. While not peptides,

codeine Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...

and

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies ('' Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. Ther ...

are also produced in the human body.

Exogenous

Exogenous opioid substances are called

exorphin Exorphins are exogenous opioid peptides, distinguished from endorphins, or endogenous opioid peptides. Exorphins include opioid food peptides like gluten exorphin and microbial opioid peptides and any other opioid peptide foreign to a host th ...

s, as opposed to

endorphine 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. Exorphins include

Gluten exorphin Gluten exorphins are a group of opioid peptides formed during the digestion of the gluten Gluten is a structural protein naturally found in certain cereal grains. Although "gluten" often only refers to wheat proteins, in medical literature it r ...

and

and are mostly contained in cereals and animal milk. They mimic the actions of

s because they bind to the same

s in the brain. These are the most common exorphins: *

Casomorphin Casomorphin is an opioid peptide (protein fragment) derived from the digestion of the milk protein casein. Health Digestive enzymes can break casein down into peptides that have some biological activity in cells and in laboratory animals though ...

(from

casein Casein ( , from Latin ''caseus'' "cheese") is a family of related phosphoproteins ( αS1, aS2, β, κ) that are commonly found in mammalian milk, comprising about 80% of the proteins in cow's milk and between 20% and 60% of the proteins in human ...

found in milk of mammals, including cows) *

(from

gluten Gluten is a structural protein naturally found in certain cereal grains. Although "gluten" often only refers to wheat proteins, in medical literature it refers to the combination of prolamin and glutelin proteins naturally occurring in all gra ...

found in

cereal A cereal is any grass cultivated for the edible components of its grain (botanically, a type of fruit called a caryopsis), composed of the endosperm, germ, and bran. Cereal grain crops are grown in greater quantities and provide more foo ...

s wheat, rye, barley) * Gliadorphin/gluteomorphin (from

found in cereals wheat, rye, barley) * Soymorphin-5 (from

soybean The soybean, soy bean, or soya bean (''Glycine max'') is a species of legume native to East Asia, widely grown for its edible bean, which has numerous uses. Traditional unfermented food uses of soybeans include soy milk, from which tofu ...

) *

Rubiscolin The rubiscolins are a group of opioid peptides that are formed during digestion of the ribulose bisphosphate carboxylase/oxygenase (Rubisco) protein from spinach leaves. These peptides have much in common with the better-known gluten exorphin Glut ...

(from

spinach Spinach (''Spinacia oleracea'') is a leafy green flowering plant native to central and western Asia. It is of the order Caryophyllales, family Amaranthaceae, subfamily Chenopodioideae. Its leaves are a common edible vegetable consumed eith ...

)

Amphibian

* Deltorphin *

Deltorphin I Deltorphin I, also known as D-Ala2.html" ;"title="small>D-Ala2">small>D-Ala2eltorphin I or deltorphin C, is a naturally occurring, exogenous opioid heptapeptide and hence, exorphin, with the amino acid sequence Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2. ...

* Deltorphin II *

Dermorphin Dermorphin is a hepta-peptide first isolated from the skin of South American frogs belonging to the genus ''Phyllomedusa''. The peptide is a natural opioid that binds as an agonist with high potency and selectivity to mu Opioid receptors. Dermorp ...

Endogenous

Exogenous

Amphibian

Synthetic

References

External links