Notes of Peptide
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• Peptide hormone
An oligopeptide (oligo-, "few") consists of a small number of amino acids linked together, as opposed to a polypeptide (poly-, "many"). Precise size range is generally up to the individual, but oligopeptides are generally accepted to be from 3 to 40 component amino acids in length.
A dipeptide is a molecule consisting of two amino acids joined by a single peptide bond. Dipeptides are produced from polypeptides by the action of the hydrolase enzyme dipeptidyl peptidase. Dietary proteins are digested to dipeptides and amino acids, and the dipeptides are absorbed more rapidly than the amino acids, because their uptake involves a separate mechanism. Dipeptides activate G-cells found in the stomach to secrete gastrin.
Examples of dipeptides:
• Carnosine (beta-alanyl-L-histidine) is highly concentrated in muscle and brain tissues.
• Anserine (beta-alanyl-N-methyl histidine) is found in the skeletal muscle and brain of mammals.
• Homoanserine (N-(4-Aminobutyryl)-L-histidine) is another dipeptide identified in the brain and muscles of mammals.
• Kyotorphin (L-tyrosyl-L-arginine) is a neuroactive dipeptide which plays a role in pain regulation in the brain.
• Balenine (or ophidine) (beta-alanyl-N tau-methyl histidine) has been identified in the muscles of several species of mammal (including man), and the chicken.
• Aspartame (N-L-a-aspartyl-L-phenylalanine 1-methyl ester) is an artificial sweetener.
• Glorin (N-propionyl-γ-L-glutamyl-L-ornithine-δ-lac ethyl ester) is a chemotactic dipeptide for the slime-mould Polysphondylium violaceum.
• Barettin (cyclo-[(6-bromo-8-en-tryptophan)-arginine]) is a cyclic dipeptide from the marine sponge Geodia barretti.
A tripeptide is a peptide consisting of three amino acids joined by peptide bonds.
Examples of tripeptides:
• Glutathione (γ-glutamyl-cysteinyl-glycine) is an antioxidant, protecting cells from toxins such as free radicals.
• Thyrotropin-releasing hormone (TRH, thyroliberin or protirelin) (L-pyroglutamyl-L-histidinyl-L-prolinamide) is a peptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary.
• Melanostatin (prolyl-leucyl-glycinamide) is a peptide hormone produced in the hypothalamus that inhibits the release of melanocyte-stimulating hormone (MSH).
• Ophthalmic acid (L-γ-glutamyl-L-α-aminobutyryl-glycine) is an analogue of glutathione isolated from crystalline lens.
• Norophthalmic acid (y-glutamyl-alanyl-glycine) is an analogue of glutathione (L-cysteine replaced by L-alanine) isolated from crystalline lens.
• Eisenin (pGlu-Gln-Ala-OH) is a peptide with immunological activity isolated from the Japanese marine alga Eisenia bicyclis.
A tetrapeptide is a peptide consisting of four amino acids joined by peptide bonds. Many tetrapeptides are pharmacologically active, often showing affinity and specificity for a variety of receptors in protein-protein signaling. Present in nature are both linear and cyclic tetrapeptides; tetrapeptides may be cyclized by a fourth peptide bond or other covalent bonds.
Examples of tetrapeptides:
• Tuftsin (L-threonyl-L-lysyl-L-prolyl-L-arginine) is a peptide related primarily to the immune system function.
• Rigin (glycyl-L-glutaminyl-L-prolyl-L-arginine) is a tetrapeptide with functions similar to those of tuftsin.
• Postin (Lys-Pro-Pro-Arg) is the N-terminal tetrapeptide of cystatin C and an antagonist of tuftsin.
• Morphiceptin (H-Tyr-Pro-Phe-Pro-NH2) is a casomorphin peptide isolated from β-casein.
• Gluten exorphines A4 (H-Gly-Tyr-Tyr-Pro-OH) and B4 (H-Tyr-Gly-Gly-Trp-OH) are peptides isolated from gluten.
• Tetragastrin (N-((phenylmethoxy)carbonyl)-L-tryptophyl-L-methionyl-L-aspartyl-L-phenylalaninamide) is the C-terminal tetrapeptide of gastrin. It is the smallest peptide fragment of gastrin which has the same physiological and pharmacological activity as gastrin.
• Kentsin (H-Thr-Pro-Arg-Lys-OH) is a contraceptive peptide first isolated from female hamsters.
• Achatin-I (glycyl-phenylalanyl-alanyl-aspartic acid) is a neuroexcitatory tetrapeptide from giant African snail (Achatina fulica).
• Tentoxin (cyclo(N-methyl-L-alanyl-L-leucyl-N-methyl-trans-dehydrophenyl-alanyl-glycyl)) is a natural cyclic tetrapeptide produced by phytopathogenic fungi from genus Alternaria.
A neuropeptide is any of the variety of peptides found in neural tissue; e.g. endorphins, enkephalins. Now, about 100 different peptides are known to be released by different populations of neurons in the mammalian brain.
Neurons use many different chemical signals to communicate information, including neurotransmitters, peptides, cannabinoids, and even some gases, like nitric oxide.
Many populations of neurons have distinctive biochemical phenotypes. For example, in one subpopulation of about 3000 neurons in the arcuate nucleus of the hypothalamus, three anorectic peptides are co-expressed: α-melanocyte-stimulating hormone (α-MSH), galanin-like peptide, and cocaine-and-amphetamine-regulated transcript (CART), and in another subpopulation two orexigenic peptides are co-expressed, neuropeptide Y and agouti-related peptide (AGRP). These are not the only peptides in the arcuate nucleus; β-endorphin, dynorphin, enkephalin, galanin, ghrelin, growth-hormone releasing hormone, neurotensin, neuromedin U, and somatostatin are also expressed in subpopulations of arcuate neurons. These peptides are all released centrally and act on other neurons at specific receptors. The neuropeptide Y neurons also make the classical inhibitory neurotransmitter GABA.
Peptide signals play a role in information processing that is different to that of conventional neurotransmitters, and many appear to be particularly associated with specific behaviors. For example, oxytocin and vasopressin have striking and specific effects on social behaviors, including maternal behavior and pair bonding.
Generally, peptides act at metabotropic or G-protein-coupled receptors expressed by selective populations of neurons - so peptides act as specific signals between one population of neurons and another. Neurotransmitters generally affect the excitability of other neurons, by depolarising them or by hyperpolarising them. Peptides have much more diverse effects; amongst other things, they can affect gene expression, local blood flow, synaptogenesis, and glial cell morphology. Peptides tend to have prolonged actions, and some have striking effects on behavior.
Neurons very often make both a conventional neurotransmitter (such as glutamate, GABA or dopamine) and one or more neuropeptides. Peptides are generally packaged in large dense-core vesicles, and the co-existing neurotransmitters in small synaptic vesicles. The large dense-core vesicles are often found in all parts of a neuron, including the soma, dendrites, axonal swellings and nerve endings, whereas the small synaptic vesicles are mainly found in clusters at presynaptic locations. Release of the large vesicles and the small vesicles is regulated differentially.
Examples of neuroactive peptides coexisting with other neurotransmitters
Transmitter names are shown in bold.
Norepinephrine (noradrenaline). In neurons of the A2 cell group in the nucleus of the solitary tract), norepinephrine co-exists with:
• Neuropeptide Y
• Somatostatin (in the hippocampus)
• Neuropeptide Y (in the arcuate nucleus)
• Substance P
• Neuropeptide Y
• Substance P
Some neurons make several different peptides. For instance, Vasopressin co-exists with dynorphin and galanin in magnocellular neurons of the supraoptic nucleus and paraventricular nucleus, and with CRF (in parvocellular neurons of the paraventricular nucleus)
Oxytocin in the supraoptic nucleus co-exists with enkephalin, dynorphin, cocaine-and amphetamine regulated transcript (CART) and cholecystokinin.
Peptide hormones are a class of peptides that are secreted into the blood stream and have endocrine functions in living animals.
Like other proteins, peptide hormones are synthesized from amino acids according to an mRNA template, which is itself synthesized from a DNA template inside the cell's nucleus. Peptide hormone precursors (pre-prohormones) are then processed in several stages, typically in the endoplasmic reticulum, including removal of the N-terminal signal sequence and sometimes glycosylation, resulting in prohormones. The prohormones are then packaged into membrane-bound secretory vesicles, which can be secreted from the cell by exocytosis in response to specific stimuli.
These prohormones often contain superfluous amino acid residues that were needed to direct folding of the hormone molecule into its active configuration but have no function once the hormone folds. Specific endopeptidases in the cell cleave the prohormone just before it is released into the blood stream, generating the mature hormone form of the molecule. Mature peptide hormones then diffuse through the blood to all of the cells of the body, where they interact with specific receptors on the surface of their target cells.
Notable peptide hormones
Several important peptide hormones are secreted from the pituitary gland. The anterior pituitary secretes luteinizing hormone and follicle stimulating hormone, which act on the gonads, prolactin, which acts on the mammary gland, adrenocorticotrophic hormone (ACTH), which acts on the adrenal cortex to regulate the secretion of glucocorticoids, and growth hormone, which acts on bone, muscle and the liver. The posterior pituitary gland secretes antidiuretic hormone, also called vasopressin, and oxytocin. Peptide hormones are produced by many different organs and tissues, however, including the heart (atrial-natriuretic peptide (ANP) or atrial natriuretic factor (ANF)) and pancreas (insulin and somatostatin), the gastrointestinal tract (cholecystokinin, gastrin), and adipose tissue stores (leptin).
Many neurotransmitters are secreted and released in a similar fashion to peptide hormones, and some 'neuropeptides' may be used as neurotransmitters in the nervous system in addition to acting as hormones when released into the blood. When a peptide hormone binds to receptors on the surface of the cell, a second messenger appears in the cytoplasm which triggers intracellular responses.