Identifiers | |
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3D model (JSmol) | |
ChEBI | |
ChemSpider | |
MeSH | Thiamine+triphosphate |
PubChem CID | |
UNII | |
CompTox Dashboard (EPA) | |
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Properties | |
C12H19N4O10P3S | |
Molar mass | 504.288 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
verify (what is ?) | |
Infobox references | |
Thiamine triphosphate (ThTP) is a biomolecule found in most organisms including bacteria, fungi, plants and animals. [1] Chemically, it is the triphosphate derivative of the vitamin thiamine.
It has been proposed that ThTP has a specific role in nerve excitability, [2] but this has never been confirmed and recent results suggest that ThTP probably plays a role in cell energy metabolism. [1] [3] Low or absent levels of thiamine triphosphate have been found in Leighs disease. [4] [5]
In E. coli , ThTP is accumulated in the presence of glucose during amino acid starvation. [1] [3] On the other hand, suppression of the carbon source leads to the accumulation, of adenosine thiamine triphosphate (AThTP).
It has been shown that in brain ThTP is synthesized in mitochondria by a chemiosmotic mechanism, perhaps similar to ATP synthase. [6] In mammals, ThTP is hydrolyzed to thiamine pyrophosphate (ThDP) by a specific thiamine-triphosphatase. [3] [7] It can also be converted into ThDP by thiamine-diphosphate kinase.
Thiamine triphosphate (ThTP) was chemically synthesized in 1948 at a time when the only organic triphosphate known was ATP. [8] The first claim of the existence of ThTP in living organisms was made in rat liver, [9] followed by baker’s yeast. [10] Its presence was later confirmed in rat tissues [11] and in plants germs, but not in seeds, where thiamine was essentially unphosphorylated. [12] In all those studies, ThTP was separated from other thiamine derivatives using a paper chromatographic method, followed by oxidation in fluorescent thiochrome compounds with ferricyanide in alkaline solution. This method is at best semi-quantitative, and the development of liquid chromatographic methods suggested that ThTP represents far less than 10% of total thiamine in animal tissues. [13]
Adenylyl cyclase is an enzyme with key regulatory roles in essentially all cells. It is the most polyphyletic known enzyme: six distinct classes have been described, all catalyzing the same reaction but representing unrelated gene families with no known sequence or structural homology. The best known class of adenylyl cyclases is class III or AC-III. AC-III occurs widely in eukaryotes and has important roles in many human tissues.
Thiamine, also known as thiamin or vitamin B1, is a vitamin found in food and manufactured as a dietary supplement and medication. Food sources of thiamine include whole grains, legumes, and some meats and fish. Grain processing removes much of the thiamine content, so in many countries cereals and flours are enriched with thiamine. Supplements and medications are available to treat and prevent thiamine deficiency and disorders that result from it, including beriberi and Wernicke encephalopathy. Other uses include the treatment of maple syrup urine disease and Leigh syndrome. They are typically taken by mouth, but may also be given by intravenous or intramuscular injection.
Succinyl coenzyme A synthetase is an enzyme that catalyzes the reversible reaction of succinyl-CoA to succinate. The enzyme facilitates the coupling of this reaction to the formation of a nucleoside triphosphate molecule from an inorganic phosphate molecule and a nucleoside diphosphate molecule. It plays a key role as one of the catalysts involved in the citric acid cycle, a central pathway in cellular metabolism, and it is located within the mitochondrial matrix of a cell.
Adenosine thiamine triphosphate (AThTP), or thiaminylated adenosine triphosphate, is a natural thiamine adenine nucleotide. It was discovered in Escherichia coli where it may account for up to 15 - 20% of total thiamine under carbon starvation. AThTP also exists in eukaryotic organisms such as yeast, roots of higher plants and animal tissues, albeit at a much lower concentration. It was found to exist in small amounts in the muscle, heart, brain, kidneys and liver of mice.
Autotaxin, also known as ectonucleotide pyrophosphatase/phosphodiesterase family member 2, is an enzyme that in humans is encoded by the ENPP2 gene.
Thiamine transporter 1, also known as thiamine carrier 1 (TC1) or solute carrier family 19 member 2 (SLC19A2) is a protein that in humans is encoded by the SLC19A2 gene. SLC19A2 is a thiamine transporter. Mutations in this gene cause thiamine-responsive megaloblastic anemia syndrome (TRMA), which is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anemia and sensorineural deafness.
Thiamine transporter 2 (ThTr-2), also known as solute carrier family 19 member 3, is a protein that in humans is encoded by the SLC19A3 gene. SLC19A3 is a thiamine transporter.
Peroxisome proliferator-activated receptor alpha (PPAR-α), also known as NR1C1, is a nuclear receptor protein that in humans is encoded by the PPARA gene. Together with peroxisome proliferator-activated receptor delta and peroxisome proliferator-activated receptor gamma, PPAR-alpha is part of the subfamily of peroxisome proliferator-activated receptors. It was the first member of the PPAR family to be cloned in 1990 by Stephen Green and has been identified as the nuclear receptor for a diverse class of rodent hepatocarcinogens that causes proliferation of peroxisomes.
Inositol 1,4,5-trisphosphate receptor type 1 is a protein that in humans is encoded by the ITPR1 gene.
The cholecystokinin B receptor also known as CCKBR or CCK2 is a protein that in humans is encoded by the CCKBR gene.
Thiamine-triphosphatase is an enzyme involved in thiamine metabolism. It catalyzes the chemical reaction
In enzymology, a polynucleotide 5'-phosphatase (RNA 5'-triphosphatase, RTPase, EC 3.1.3.33) is an enzyme that catalyzes the chemical reaction
Alpha II-spectrin, also known as Spectrin alpha chain, brain is a protein that in humans is encoded by the SPTAN1 gene. Alpha II-spectrin is expressed in a variety of tissues, and is highly expressed in cardiac muscle at Z-disc structures, costameres and at the sarcolemma membrane. Mutations in alpha II-spectrin have been associated with early infantile epileptic encephalopathy-5, and alpha II-spectrin may be a valuable biomarker for Guillain–Barré syndrome and infantile congenital heart disease.
Plasma membrane calcium-transporting ATPase 4 is an enzyme that in humans is encoded by the ATP2B4 gene.
Cytoglobin is the protein product of CYGB, a human and mammalian gene.
Inosine triphosphate pyrophosphatase is an enzyme that in humans is encoded by the ITPA gene, by the rdgB gene in bacteria E.coli and the HAM1 gene in yeast S. cerevisiae. Two transcript variants encoding two different isoforms have been found for this gene. Also, at least two other transcript variants have been identified which are probably regulatory rather than protein-coding.
The mitochondrial dicarboxylate carrier (DIC) is an integral membrane protein encoded by the SLC25A10 gene in humans that catalyzes the transport of dicarboxylates such as malonate, malate, and succinate across the inner mitochondrial membrane in exchange for phosphate, sulfate, and thiosulfate by a simultaneous antiport mechanism, thus supplying substrates for the Krebs cycle, gluconeogenesis, urea synthesis, fatty acid synthesis, and sulfur metabolism.
SAM domain and HD domain-containing protein 1 is a protein that in humans is encoded by the SAMHD1 gene. SAMHD1 is a cellular enzyme, responsible for blocking replication of HIV in dendritic cells, macrophages, monocytes and resting CD4+ T lymphocytes. It is an enzyme that exhibits phosphohydrolase activity, converting deoxynucleoside triphosphates (dNTPs) to inorganic phosphate (iPPP) and a 2'-deoxynucleoside. In doing so, SAMHD1 depletes the pool of dNTPs available to a reverse transcriptase for viral cDNA synthesis and thus prevents viral replication. SAMHD1 has also shown nuclease activity. Although a ribonuclease activity was described to be required for HIV-1 restriction, recent data confirmed that SAMHD1-mediated HIV-1 restriction in cells does not involve ribonuclease activity.
Hemopressin (Hp) is an alpha hemoglobin fragment with the sequence PVNFKFLSH, originally identified in extracts of rat brain using an enzyme capture technique. It binds cannabinoid receptors, acting as an inverse agonist at CB1 receptors. Longer forms of hemopressin containing 2-3 additional amino acids on the N-terminus have been identified in extracts of mouse brain. These longer hemopressin peptides, named RVD-Hpα and VD-Hpα, bind to CB1 receptors and were originally reported to be agonists. In addition to the Hp peptides from alpha hemoglobin, a related peptide from beta hemoglobin has been found in mouse brain extracts; this peptide, named VD-Hpβ, is also an agonist at CB1 cannabinoid receptors. Hemopressin is not an endogenous peptide but rather an extraction artefact [Bauer M, Chicca A, Tamborrini M, Eisen D, Lerner R, Lutz B, Poetz O, Pluschke G, Gertsch J. Identification and quantification of a new family of peptide endocannabinoids (Pepcans) showing negative allosteric modulation at CB1 receptors. J Biol Chem. 2012 Oct 26;287(44):36944-67. doi: 10.1074/jbc.M112.382481. Epub 2012 Sep 5.]. The only endogenous peptide found endogenously at physiological conditions is RVD-hemopressin (pepcan-12), which has more recently been shown to be a negative allosteric modulator of CB1 receptors and positive allosteric modulator of CB2 receptors [Bauer M, Chicca A, Tamborrini M, Eisen D, Lerner R, Lutz B, Poetz O, Pluschke G, Gertsch J. Identification and quantification of a new family of peptide endocannabinoids (Pepcans) showing negative allosteric modulation at CB1 receptors. J Biol Chem. 2012 Oct 26;287(44):36944-67. doi: 10.1074/jbc.M112.382481. Epub 2012 Sep 5.] [Petrucci V, Chicca A, Glasmacher S, Paloczi J, Cao Z, Pacher P, Gertsch J. Pepcan-12 (RVD-hemopressin) is a CB2 receptor positive allosteric modulator constitutively secreted by adrenals and in liver upon tissue damage. Sci Rep. 2017 Aug 25;7(1):9560. doi: 10.1038/s41598-017-09808-8.]. RVD-hemopressin (pepcan-12) is generated from a pro-peptide called pepcan-23 and these peptides are exclusively found in noradrenergic neurons in the brain and in the adrenal medulla [Hofer SC, Ralvenius WT, Gachet MS, Fritschy JM, Zeilhofer HU, Gertsch J. Localization and production of peptide endocannabinoids in the rodent CNS and adrenal medulla. Neuropharmacology. 2015 Nov;98:78-89. doi: 10.1016/j.neuropharm.2015.03.021. Epub 2015 Mar 31.]
2-hydroxy-dATP diphosphatase is an enzyme that in humans is encoded by the NUDT1 gene. During DNA repair, the enzyme hydrolyses oxidized purines and prevents their addition onto the DNA chain. As such it has important role in aging and cancer development.