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CYP2D6
Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra. CYP2D6, a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. In particular, CYP2D6 is responsible for the metabolism and elimination of approximately 25% of clinically used drugs, via the addition or removal of certain functional groups – specifically, hydroxylation, demethylation, and dealkylation. CYP2D6 also activates some prodrugs. This enzyme also metabolizes several endogenous substances, such as hydroxytryptamines, neurosteroids, and both ''m''-tyramine and ''p''-tyramine which CYP2D6 metabolizes into dopamine in the brain and liver. Considerable variation exists in the efficiency and amount of CYP2D6 enzyme produced betwee ...
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M-tyramine
''meta''-Tyramine, also known as ''m''-tyramine and 3-tyramine, is an endogenous trace amine neuromodulator and a structural analog of phenethylamine. It is a positional isomer of ''para''-tyramine, and similarly to it, has effects on the adrenergic and dopaminergic systems. ''meta''-Tyramine is produced in humans via aromatic amino acid decarboxylase-mediated metabolism of ''meta''-tyrosine. meta-Tyramine can be metabolized into dopamine via peripheral or brain CYP2D6 enzymes in humans. See also * ''para''-Tyramine * 3-Methoxytyramine 3-Methoxytyramine (3-MT), also known as 3-methoxy-4-hydroxyphenethylamine, is a human trace amine that occurs as a metabolite of the neurotransmitter dopamine. It is formed by the introduction of a methyl group to dopamine by the enzyme cate ... References Phenethylamines Phenols TAAR1 agonists Trace amines Norepinephrine-dopamine releasing agents {{nervous-system-drug-stub ...
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Dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% of the catecholamine content in the brain. It is an amine synthesized by removing a carboxyl group from a molecule of its precursor chemical, L-DOPA, which is synthesized in the brain and kidneys. Dopamine is also synthesized in plants and most animals. In the brain, dopamine functions as a neurotransmitter—a chemical released by neurons (nerve cells) to send signals to other nerve cells. Neurotransmitters are synthesized in specific regions of the brain, but affect many regions systemically. The brain includes several distinct dopamine pathways, one of which plays a major role in the motivational component of reward-motivated behavior. The anticipation of most types of rewards increases the level of dopamine in the brain, and many ad ...
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Tyramine
Tyramine ( ) (also spelled tyramin), also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the blood-brain barrier, resulting in only non-psychoactive peripheral sympathomimetic effects following ingestion. A hypertensive crisis can result, however, from ingestion of tyramine-rich foods in conjunction with the use of monoamine oxidase inhibitors (MAOIs). Occurrence Tyramine occurs widely in plants and animals, and is metabolized by various enzymes, including monoamine oxidases. In foods, it often is produced by the decarboxylation of tyrosine during fermentation or decay. Foods that are fermented, cured, pickled, aged, or spoiled have high amounts of tyramine. Tyramine levels go up when foods are at room temperature or go past their freshness date. Specific foods containing considerable amounts of tyramine include: * strong or aged ...
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Cytochrome P450
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown. In 1963, Estabrook, Cooper, and Rosenthal described the role of CYP as a catalyst in steroid hormone synthesis and drug metabolism. In plants, these proteins are important for the biosynthesis of defensive compounds, fatty acids, and hormones. CYP enzymes have been identified in all kingdoms of life: animals, plants, fungi, protists, bacteria, and archaea, as well as in viruses. However, they are not omnipresent; for example, they have not been found in ''Escherichia coli''. , more than 300,000 distinct CYP proteins are known. CYPs are, in general, the terminal oxidase enzymes in electron transfer chains, broadly categorized as P450-containing systems. The term "P450" is deriv ...
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Drug Interaction
Drug interactions occur when a drug's mechanism of action is disturbed by the concomitant administration of substances such as foods, beverages, or other drugs. The cause is often the inhibition of the specific receptors available to the drug, forcing the drug molecules to bind to other non-intended targets which results in an array of side-effects. The term selectivity describes a drug’s ability to target a single receptor, rendering a predictable physiological response. For example, the binding of acetylcholine to muscarinic tracheal smooth-muscle receptors (M3) results in smooth muscle contractions. When free receptors become occupied by agonists - drugs that bind and activate receptors - and antagonists - drugs that inhibit/ block activation - the opportunity for drugs to target their intended receptor decreases as most receptors are already occupied. Therefore, when the number of free receptors decreases, the drugs begin binding to other secondary receptors, caus ...
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Phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological properties, its behavior, and the products of behavior. An organism's phenotype results from two basic factors: the expression of an organism's genetic code, or its genotype, and the influence of environmental factors. Both factors may interact, further affecting phenotype. When two or more clearly different phenotypes exist in the same population of a species, the species is called polymorphic. A well-documented example of polymorphism is Labrador Retriever coloring; while the coat color depends on many genes, it is clearly seen in the environment as yellow, black, and brown. Richard Dawkins in 1978 and then again in his 1982 book '' The Extended Phenotype'' suggested that one can regard bird nests and other built structures such as ...
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Isoform
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have unique functions. A set of protein isoforms may be formed from alternative splicings, variable promoter usage, or other post-transcriptional modifications of a single gene; post-translational modifications are generally not considered. (For that, see Proteoforms.) Through RNA splicing mechanisms, mRNA has the ability to select different protein-coding segments ( exons) of a gene, or even different parts of exons from RNA to form different mRNA sequences. Each unique sequence produces a specific form of a protein. The discovery of isoforms could explain the discrepancy between the small number of protein coding regions genes revealed by the human genome project and the large diversity of proteins seen in an organism: differ ...
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Alternative Splicing
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be included within or excluded from the final, processed messenger RNA (mRNA) produced from that gene. This means the exons are joined in different combinations, leading to different (alternative) mRNA strands. Consequently, the proteins translated from alternatively spliced mRNAs will contain differences in their amino acid sequence and, often, in their biological functions (see Figure). Biologically relevant alternative splicing occurs as a normal phenomenon in eukaryotes, where it increases the number of proteins that can be encoded by the genome. In humans, it is widely believed that ~95% of multi-exonic genes are alternatively spliced to produce functional alternative products from the same gene but many scientists believe that most of ...
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New World Monkey
New World monkeys are the five families of primates that are found in the tropical regions of Mexico, Central and South America: Callitrichidae, Cebidae, Aotidae, Pitheciidae, and Atelidae. The five families are ranked together as the Ceboidea (), the only extant superfamily in the parvorder Platyrrhini (). Platyrrhini is derived from the Greek for "broad nosed", and their noses are flatter than those of other simians, with sideways-facing nostrils. Monkeys in the family Atelidae, such as the spider monkey, are the only primates to have prehensile tails. New World monkeys' closest relatives are the other simians, the Catarrhini ("down-nosed"), comprising Old World monkeys and apes. New World monkeys descend from African simians that colonized South America, a line that split off about 40 million years ago. Evolutionary history About 40 million years ago, the Simiiformes infraorder split into the parvorders Platyrrhini (New World monkeys) and Catarrhini ( apes and Old Worl ...
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Catarrhine
The parvorder Catarrhini , catarrhine monkeys, Old World anthropoids, or Old World monkeys, consisting of the Cercopithecoidea and apes (Hominoidea). In 1812, Geoffroy grouped those two groups together and established the name Catarrhini, "Old World monkeys", ("''singes de l'Ancien Monde''" in French). Its sister in the infraorder Simiiformes is the parvorder Platyrrhini (New World monkeys). There has been some resistance to directly designate apes (and thus humans) as monkeys despite the scientific evidence, so "Old World monkey" may be taken to mean the Cercopithecoidea or the Catarrhini. That apes are monkeys was already realized by Georges-Louis Leclerc, Comte de Buffon in the 18th century. Linnaeus placed this group in 1758 together with what we now recognise as the tarsiers and the New World monkeys, in a single genus " S''imia''" (sans '' Homo''). The Catarrhini are all native to Africa and Asia. Members of this parvorder are called catarrhines. The Catarrhini are the ...
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Pseudogene
Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Most arise as superfluous copies of functional genes, either directly by DNA duplication or indirectly by reverse transcription of an mRNA transcript. Pseudogenes are usually identified when genome sequence analysis finds gene-like sequences that lack regulatory sequences needed for transcription or translation, or whose coding sequences are obviously defective due to frameshifts or premature stop codons. Most non-bacterial genomes contain many pseudogenes, often as many as functional genes. This is not surprising, since various biological processes are expected to accidentally create pseudogenes, and there are no specialized mechanisms to remove them from genomes. Eventually pseudogenes may be deleted from their genomes by chance DNA replication or DNA repair errors, or they may accumulate so many mutational changes that they are no longer recognizable as former genes. Analysis of these degenerati ...
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Chromosome 22
Chromosome 22 is one of the 23 pairs of chromosomes in human cells. Humans normally have two copies of chromosome 22 in each cell. Chromosome 22 is the second smallest human chromosome, spanning about 49 million DNA base pairs and representing between 1.5 and 2% of the total DNA in cells. In 1999, researchers working on the Human Genome Project announced they had determined the sequence of base pairs that make up this chromosome. Chromosome 22 was the first human chromosome to be fully sequenced. Human chromosomes are numbered by their apparent size in the karyotype, with Chromosome 1 being the largest and Chromosome 22 having originally been identified as the smallest. However, genome sequencing has revealed that Chromosome 21 is actually smaller than Chromosome 22. Genes Number of genes The following are some of the gene count estimates of human chromosome 22. Because researchers use different approaches to genome annotation, their predictions of the number of genes on ea ...
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