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Contryphan
The contryphans (conus + tryptophan) are a family of peptides that are active constituents of the potent venom produced by cone snail (genus ''Conus''). The two amino acid cysteine residues in contryphans are linked by a disulfide bond. In addition, contryphans undergo an unusual degree of post-translational modification including epimerization of leucine and tryptophan, tryptophan bromination, amidation of the C-terminus, and proline hydroxylation. In the broader scheme of genetic conotoxin classification, contryphans are members of "Conotoxin Superfamily O2." Family members Contryphan family members include: where the sequence abbreviations stand for: * O = 4-trans-hydroxyproline, * l = D-leucine, L = L-leucine, * w = D-tryptophan, W = L-tryptophan, * γ = gamma-carboxyglutamic acid, * NH2 = C-terminal amidation and the remainder of the letters refer to the standard one letter abbreviations for amino acids. Mechanism of toxicity The venom of cone snails cause paralys ...
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Conus Ventricosus
''Conus ventricosus'', common name the Mediterranean cone, is a species of sea snail, a marine gastropod mollusk in the family Conidae, the cone snails and their allies. * '' Conus ventricosus mediterraneus'' Hwass in Bruguière, 1792, is a recognized subspecies. Like all species within the genus ''Conus'', these snails are predatory and venomous. They are capable of "stinging" humans, therefore live ones should be handled carefully or not at all. Description The size of the shell varies between 13 mm and 63 mm. The shell is yellowish brown, pink-brown or olivaceous. It is sometimes chocolate-brown, very closely nebulously spotted and reticulated. And sometimes it is interrupted-lined with chestnut, with a narrow, light band below the middle. The spire is elevated, rudely gradate and maculated. The interior of the aperture is light chocolate, with a light band. The peptide Contryphan-Vn was extracted from the venom of this marine snail. It is part of a complex mixtur ...
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Conotoxin
A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail, genus ''Conus''. Conotoxins, which are peptides consisting of 10 to 30 amino acid residues, typically have one or more disulfide bonds. Conotoxins have a variety of mechanisms of actions, most of which have not been determined. However, it appears that many of these peptides modulate the activity of ion channels. Over the last few decades conotoxins have been the subject of pharmacological interest. The LD50 of conotoxin ranges from 5-25 μg/kg. Hypervariability Conotoxins are hypervariable even within the same species. They do not act within a body where they are produced (endogenously) but act on other organisms. Therefore, conotoxin genes experience less selection against mutations (like gene duplication and nonsynonymous substitution), and mutations remain in the genome longer, allowing more time for potentially beneficial novel functions to arise. Variability in c ...
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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. A polypeptide is a longer, continuous, unbranched peptide chain. Hence, peptides fall under the broad chemical classes of biological polymers and oligomers, alongside nucleic acids, oligosaccharides, polysaccharides, and others. A polypeptide that contains more than approximately 50 amino acids is known as a protein. Proteins consist of one or more polypeptides arranged in a biologically functional way, often bound to ligands such as coenzymes and cofactors, or to another protein or other macromolecule such as DNA or RNA, or to complex macromolecular assemblies. Amino acids that have been incorporated into peptides are termed residues. A water molecule is released during formation of each amide bond.. All peptides except cyclic pep ...
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Conus Stercusmuscarum
''Conus stercusmuscarum'', common name the fly-specked cone, is a species of sea snail, a marine gastropod mollusk in the family Conidae, the cone snails and their allies. These snails are predatory and venomous. They are capable of "stinging" humans, therefore live ones should be handled carefully or not at all. Description The size of the shell varies between 27 mm and 64 mm. Distribution This piscivorous species occurs in the Western Pacific Ocean: Fiji, Marshall Islands, Papua New Guinea, Solomon Islands; also off Indonesia, Japan, Taiwan, the Philippines and Australia (Northern Territory, Queensland ) , nickname = Sunshine State , image_map = Queensland in Australia.svg , map_caption = Location of Queensland in Australia , subdivision_type = Country , subdivision_name = Australia , established_title = Before federation , established_ ...). Gallery File:Conus stercusmuscarum 3.jpg, ''Conus stercusmuscarum'' Linnaeus, C., 1758 File:Conus stercusmuscar ...
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Neurotoxins
Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature nervous tissue.Olney 2002 The term can also be used to classify endogenous compounds, which, when abnormally contacted, can prove neurologically toxic. Though neurotoxins are often neurologically destructive, their ability to specifically target neural components is important in the study of nervous systems. Common examples of neurotoxins include lead, ethanol (drinking alcohol), glutamate,Choi 1987 nitric oxide, botulinum toxin (e.g. Botox), tetanus toxin,Simpson 1986 and tetrodotoxin. Some substances such as nitric oxide and glutamate are in fact essential for proper function of the body and only exert neurotoxic effects at excessive concentrations. Neurotoxins inhibit neuron control over ion concentrations across the cell membrane, or c ...
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L-type Calcium Channel
The L-type calcium channel (also known as the dihydropyridine channel, or DHP channel) is part of the high-voltage activated family of voltage-dependent calcium channel. "L" stands for long-lasting referring to the length of activation. This channel has four isoforms: Cav1.1, Cav1.2, Cav1.3, and Cav1.4. L-type calcium channels are responsible for the excitation-contraction coupling of skeletal, smooth, cardiac muscle, and for aldosterone secretion in endocrine cells of the adrenal cortex. They are also found in neurons, and with the help of L-type calcium channels in endocrine cells, they regulate neurohormones and neurotransmitters. They have also been seen to play a role in gene expression, mRNA stability, neuronal survival, ischemic-induced axonal injury, synaptic efficacy, and both activation and deactivation of other ion channels. In cardiac myocytes, the L-type calcium channel passes inward Ca2+ current (ICaL) and triggers calcium release from the sarcoplasmic reticul ...
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Calcium-activated Potassium Channel
Calcium-activated potassium channels are potassium channels gated by calcium, or that are structurally or phylogenetically related to calcium gated channels. They were first discovered in 1958 by Gardos who saw that calcium levels inside of a cell could affect the permeability of potassium through that cell membrane. Then in 1970, Meech was the first to observe that intracellular calcium could trigger potassium currents. In humans they are divided into three subtypes: BK channel, large conductance or BK channels, which have very high conductance which range from 100 to 300 pS, intermediate conductance or IK channels, with intermediate conductance ranging from 25 to 100 pS, and small conductance or SK channels with small conductances from 2-25 pS. This family of ion channels is, for the most part, activated by intracellular Ca2+ and contains 8 members in the human genome. However, some of these channels (the KCa4 and KCa5 channels) are responsive instead to other intracellular ligan ...
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Paralysis
Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 50 people have been diagnosed with some form of permanent or transient paralysis. The word "paralysis" derives from the Greek παράλυσις, meaning "disabling of the nerves" from παρά (''para'') meaning "beside, by" and λύσις (''lysis'') meaning "making loose". A paralysis accompanied by involuntary tremors is usually called "palsy". Causes Paralysis is most often caused by damage in the nervous system, especially the spinal cord. Other major causes are stroke, trauma with nerve injury, poliomyelitis, cerebral palsy, peripheral neuropathy, Parkinson's disease, ALS, botulism, spina bifida, multiple sclerosis, and Guillain–Barré syndrome. Temporary paralysis occurs during REM sleep, and dysregulation of this system can lead ...
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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 amino acids appear in the genetic code. Amino acids can be classified according to the locations of the core structural functional groups, as Alpha and beta carbon, alpha- , beta- , gamma- or delta- amino acids; other categories relate to Chemical polarity, polarity, ionization, and side chain group type (aliphatic, Open-chain compound, acyclic, aromatic, containing hydroxyl or sulfur, etc.). In the form of proteins, amino acid '' residues'' form the second-largest component (water being the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. It is thought that they played a key role in enabling life ...
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Gamma-carboxyglutamic Acid
Carboxyglutamic acid (or the conjugate base, carboxyglutamate), is an uncommon amino acid introduced into proteins by a post-translational carboxylation of glutamic acid residues. This modification is found, for example, in clotting factors and other proteins of the coagulation cascade. This modification introduces an affinity for calcium ions. In the blood coagulation cascade, vitamin K is required to introduce γ-carboxylation of clotting factors II, VII, IX, X and protein Z. Synthesis In the biosynthesis of γ-carboxyglutamic acid, the γ-proton on glutamic acid is abstracted, and CO2 is subsequently added. The reaction intermediate is a γ-glutamyl carbanion. This reaction is catalyzed by a carboxylase that requires vitamin K as its cofactor. It is not exactly known how vitamin K participates, but it is hypothesized that a free cysteine residue in the carboxylase converts vitamin K into an active strong base that in turn abstracts a hydrogen from glutamic acid's γ-carbon. T ...
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L-tryptophan
Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an Alpha_and_beta_carbon , α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar Aromatic hydrocarbon, aromatic Alpha and beta carbon, beta carbon substituent. It is Essential amino acid, essential in humans, meaning that the body cannot synthesize it and it must be obtained from the diet. Tryptophan is also a precursor to the neurotransmitter serotonin, the hormone melatonin, and vitamin B3. It is Genetic code, encoded by the codon UGG. Like other amino acids, tryptophan is a zwitterion at physiological pH where the amino group is protonated (–; pKa = 9.39) and the carboxylic acid is deprotonation, deprotonated ( –COO−; pKa = 2.38). Humans and many animals cannot synthesize tryptophan: they need to obtain it through their diet, making it an essential amino acid. Function Amino acids, including ...
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L-leucine
Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- carboxylic acid group (which is in the deprotonated −COO− form under biological conditions), and a side chain isobutyl group, making it a non-polar aliphatic amino acid. It is essential in humans, meaning the body cannot synthesize it: it must be obtained from the diet. Human dietary sources are foods that contain protein, such as meats, dairy products, soy products, and beans and other legumes. It is encoded by the codons UUA, UUG, CUU, CUC, CUA, and CUG. Like valine and isoleucine, leucine is a branched-chain amino acid. The primary metabolic end products of leucine metabolism are acetyl-CoA and acetoacetate; consequently, it is one of the two exclusively ketogenic amino acids, with lysine being the other. It is the most important ...
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