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Tryptophan Hydroxylase
Tryptophan hydroxylase (TPH) is an enzyme () involved in the synthesis of the neurotransmitter serotonin. Tyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylase together constitute the family of biopterin-dependent aromatic amino acid hydroxylases. TPH catalyzes the following chemical reaction : L-tryptophan + tetrahydrobiopterin + O2 \rightleftharpoons 5-Hydroxytryptophan + dihydrobiopterin + H2O It employs one additional cofactor, iron. Function It is responsible for addition of the -OH group ( hydroxylation) to the 5 position to form the amino acid 5-hydroxytryptophan (5-HTP), which is the initial and rate-limiting step in the synthesis of the neurotransmitter serotonin. It is also the first enzyme in the synthesis of melatonin. Tryptophan hydroxylase (TPH), tyrosine hydroxylase (TH) and phenylalanine hydroxylase (PAH) are members of a superfamily of aromatic amino acid hydroxylases, catalyzing key steps in important metabolic pathways. An ...
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TPH1
Tryptophan hydroxylase 1 (TPH1) is an isoenzyme of tryptophan hydroxylase which in humans is encoded by the ''TPH1'' gene. TPH1 was first discovered to synthesize serotonin in 1988 and was thought that there only was a single ''TPH'' gene until 2003, while a second form was found in the mouse (''Tph2''), rat and human brain (TPH2) and the original TPH was then renamed to TPH1. Function Tryptophan hydroxylases catalyze the biopterin-dependent monooxygenation of tryptophan to 5-hydroxytryptophan (5-HTP), which is subsequently decarboxylated to form the neurotransmitter serotonin (5-hydroxytryptamine or 5-HT). It is the rate-limiting enzyme in the biosynthesis of serotonin. TPH expression is limited to a few specialized tissues: raphe neurons, pinealocytes, mast cells, mononuclear leukocytes, beta-cells of the islets of Langerhans, and intestinal and pancreatic enterochromaffin cells. Clinical significance Tryptophan hydroxylase is important for synthesizing indoleamine n ...
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Tetrahydrobiopterin
Tetrahydrobiopterin (BH4, THB), also known as sapropterin (INN), is a cofactor of the three aromatic amino acid hydroxylase enzymes, used in the degradation of amino acid phenylalanine and in the biosynthesis of the neurotransmitters serotonin (5-hydroxytryptamine, 5-HT), melatonin, dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), and is a cofactor for the production of nitric oxide (NO) by the nitric oxide synthases. Chemically, its structure is that of a (dihydropteridine reductase) reduced pteridine derivative (quinonoid dihydrobiopterin). Medical use Tetrahydrobiopterin is available as a tablet for oral administration in the form of ''sapropterin dihydrochloride'' (BH4*2HCL). It was approved for use in the United States as a tablet in December 2007 and as a powder in December 2013. It was approved for use in the European Union in December 2008, Canada in April 2010, and Japan in July 2008. It is sold under the brand names Kuvan and Biopten. The typica ...
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Neuronal
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. Non-animals like plants and fungi do not have nerve cells. Neurons are typically classified into three types based on their function. Sensory neurons respond to stimuli such as touch, sound, or light that affect the cells of the sensory organs, and they send signals to the spinal cord or brain. Motor neurons receive signals from the brain and spinal cord to control everything from muscle contractions to glandular output. Interneurons connect neurons to other neurons within the same region of the brain or spinal cord. When multiple neurons are connected together, they form what is called a neural circuit. A typical neuron consists of a cell body (soma), dendrites, and a single axon. The soma is a compact structure, and the axon and dendri ...
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Pineal Gland
The pineal gland, conarium, or epiphysis cerebri, is a small endocrine gland in the brain of most vertebrates. The pineal gland produces melatonin, a serotonin-derived hormone which modulates sleep patterns in both circadian and seasonal cycles. The shape of the gland resembles a pine cone, which gives it its name. The pineal gland is located in the epithalamus, near the center of the brain, between the two hemispheres, tucked in a groove where the two halves of the thalamus join. The pineal gland is one of the neuroendocrine secretory circumventricular organs in which capillaries are mostly permeable to solutes in the blood. Nearly all vertebrate species possess a pineal gland. The most important exception is a primitive vertebrate, the hagfish. Even in the hagfish, however, there may be a "pineal equivalent" structure in the dorsal diencephalon. The lancelet '' Branchiostoma lanceolatum'', an early chordate which is a close relative to vertebrates, also lacks a ...
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Gut (zoology)
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and other animals, including the esophagus, stomach, and intestines. Food taken in through the mouth is digested to extract nutrients and absorb energy, and the waste expelled at the anus as feces. ''Gastrointestinal'' is an adjective meaning of or pertaining to the stomach and intestines. Most animals have a "through-gut" or complete digestive tract. Exceptions are more primitive ones: sponges have small pores ( ostia) throughout their body for digestion and a larger dorsal pore (osculum) for excretion, comb jellies have both a ventral mouth and dorsal anal pores, while cnidarians and acoels have a single pore for both digestion and excretion. The human gastrointestinal tract consists of the esophagus, stomach, and intestines, and is divi ...
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Skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different developmental origin, structure and chemical composition. The adjective cutaneous means "of the skin" (from Latin ''cutis'' 'skin'). In mammals, the skin is an organ of the integumentary system made up of multiple layers of ectodermal tissue and guards the underlying muscles, bones, ligaments, and internal organs. Skin of a different nature exists in amphibians, reptiles, and birds. Skin (including cutaneous and subcutaneous tissues) plays crucial roles in formation, structure, and function of extraskeletal apparatus such as horns of bovids (e.g., cattle) and rhinos, cervids' antlers, giraffids' ossicones, armadillos' osteoderm, and os penis/ os clitoris. All mammals have some hair on their skin, even marine mammals like whales, ...
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Protein Kinase A
In cell biology, protein kinase A (PKA) is a family of enzymes whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase (). PKA has several functions in the cell, including regulation of glycogen, sugar, and lipid metabolism. It should not be confused with 5'-AMP-activated protein kinase ( AMP-activated protein kinase). History Protein kinase A, more precisely known as adenosine 3',5'-monophosphate (cyclic AMP)-dependent protein kinase, abbreviated to PKA, was discovered by chemists Edmond H. Fischer and Edwin G. Krebs in 1968. They won the Nobel Prize in Physiology or Medicine in 1992 for their work on phosphorylation and dephosphorylation and how it relates to PKA activity. PKA is one of the most widely researched protein kinases, in part because of its uniqueness; out of 540 different protein kinase genes that make up the human kinome, only one other protein kinase, casein kinase 2, is known to exist in a phy ...
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Phosphorylation
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, which is available under a Creative Commons Attribution 4.0 International License. Protein phosphorylation often activates (or deactivates) many enzymes. Glucose Phosphorylation of sugars is often the first stage in their catabolism. Phosphorylation allows cells to accumulate sugars because the phosphate group prevents the molecules from diffusing back across their transporter. Phosphorylation of glucose is a key reaction in sugar metabolism. The chemical equation for the conversion of D-glucose to D-glucose-6-phosphate in the first step of glycolysis is given by :D-glucose + ATP → D-glucose-6-phosphate + ADP : ΔG° = −16.7 kJ/mol (° indicates measurement at standard condition) Hepatic cells are freely permeable to glucose, and t ...
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Enzyme Activity
Enzyme assays are laboratory methods for measuring enzymatic activity. They are vital for the study of enzyme kinetics and enzyme inhibition. Enzyme units The quantity or concentration of an enzyme can be expressed in molar amounts, as with any other chemical, or in terms of activity in enzyme units. Enzyme activity Enzyme activity is a measure of the quantity of active enzyme present and is thus dependent on various physical conditions, ''which should be specified''. It is calculated using the following formula: :\operatorname=\operatorname=\operatorname\times\operatorname where :\operatorname= Enzyme activity :\operatorname= Moles of substrate converted per unit time :\operatorname= Rate of the reaction :\operatorname= Reaction volume The SI unit is the katal, 1 katal = 1  mol s−1 (mole per second), but this is an excessively large unit. A more practical and commonly used value is enzyme unit (U) = 1 μmol min−1 (micromole per minute). 1 U corresponds to 16.67 ...
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P-Chlorophenylalanine
Fenclonine, also known as ''para''-chlorophenylalanine (PCPA), acts as a selective and irreversible inhibitor of tryptophan hydroxylase, which is a rate-limiting enzyme in the biosynthesis of serotonin. It has been used experimentally to treat carcinoid syndrome, but the side effects, mostly hypersensitivity reactions and psychiatric disturbances, have prevented development for this use. The effects of serotonin depletion from fenclonine are so drastic that serotonin cannot even be detected immunohistochemically within the first day after administration of a control dose. Tryptophan hydroxylase activity can be detected neither in cell bodies or nerve terminals. After one week 10% of control values (the baseline extrapolated for the study) had replenished in the raphe nucleus, and after two weeks from initial treatment as much was again detected in the hypothalamus region. Aromatic L-amino acid decarboxylase (AADC) levels were at no time affected. It is used in scientific rese ...
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Tyrosine Hydroxylase
Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA). It does so using molecular oxygen (O2), as well as iron (Fe2+) and tetrahydrobiopterin as cofactors. L-DOPA is a precursor for dopamine, which, in turn, is a precursor for the important neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline). Tyrosine hydroxylase catalyzes the rate limiting step in this synthesis of catecholamines. In humans, tyrosine hydroxylase is encoded by the ''TH'' gene, and the enzyme is present in the central nervous system (CNS), peripheral sympathetic neurons and the adrenal medulla. Tyrosine hydroxylase, phenylalanine hydroxylase and tryptophan hydroxylase together make up the family of aromatic amino acid hydroxylases (AAAHs). Reaction Tyrosine hydroxylase catalyzes the reaction in which L-tyrosine is hydroxylated in the meta position to obtain L- ...
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5-hydroxytryptophan
5-Hydroxytryptophan (5-HTP), also known as oxitriptan, is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitter serotonin. Uses 5-HTP is sold over the counter in the United States, Canada, Singapore, the Netherlands, and the United Kingdom as a dietary supplement for use as an antidepressant, appetite suppressant, and sleep aid. It is also marketed in many European countries for the indication of major depression under the trade names Cincofarm, Levothym, Levotonine, Oxyfan, Telesol, Tript-OH, and Triptum. A 2002 review concluded that although the data evaluated suggests that 5-HTP is more effective than placebo in the treatment of depression, the evidence was insufficient to be conclusive due to a lack of clinical data meeting the rigorous standards of the day. More and larger studies using current methodologies are needed to determine if 5-HTP is truly effective in treating depression. In ...
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