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| Identifiers | |
|---|---|
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). | |
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 Leigh's 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]
Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient for humans and animals. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosphorylated forms of thiamine are required for some metabolic reactions, including the breakdown of glucose and amino acids.
Leigh syndrome is an inherited neurometabolic disorder that affects the central nervous system. It is named after Archibald Denis Leigh, a British neuropsychiatrist who first described the condition in 1951. Normal levels of thiamine, thiamine monophosphate, and thiamine diphosphate are commonly found, but there is a reduced or absent level of thiamine triphosphate. This is thought to be caused by a blockage in the enzyme thiamine-diphosphate kinase, and therefore treatment in some patients would be to take thiamine triphosphate daily. While the majority of patients typically exhibit symptoms between the ages of 3 and 12 months, instances of adult onset have also been documented.
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.
Thiamine monophosphate, also known as ThMP and TMP, is a phosphate ester of thiamine.
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 functioning as a transcription factor 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.
Intersectin-1 is a protein that, in humans, is encoded by the ITSN1 gene.
Neuropeptide Y receptor type 2 (Y2R) is a member of the neuropeptide Y receptor family of G-protein coupled receptors, that in humans is encoded by the NPY2R gene.
Thiamine-triphosphatase is an enzyme involved in thiamine metabolism. It catalyzes the chemical reaction
The enzyme polynucleotide 5′-phosphatase (RNA 5′-triphosphatase, RTPase, EC 3.1.3.33) is an enzyme that catalyzes the 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.
Ubiquitin-conjugating enzyme E2 L3 (UBE2L3), also called UBCH7, is a protein that in humans is encoded by the UBE2L3 gene. As an E2 enzyme, UBE2L3 participates in ubiquitination to target proteins for degradation. The role of UBE2L3 in the ubiquitination of the NF-κB precursor implicated it in various major autoimmune diseases, including rheumatoid arthritis (RA), celiac disease, Crohn's disease (CD), and systemic lupus erythematosus.
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; the protein is also encoded by some RNA viruses of the Potyviridae family. 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 (i.e. deoxynucleosides without a phosphate group). 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.
Adenosine thiamine diphosphate (AThDP), or thiaminylated adenosine diphosphate (ADP) is a naturally occurring thiamine adenine nucleotide. It was chemically synthesized and exists in small amounts in vertebrate liver. Its biological significance remains unknown.
