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| thiamine(1+) triphosphate |
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| CHEBI:9534 |
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| A thiamine phosphate that is thiamine(1+) in which the hydroxy group is replaced by a triphosphate group. It is found in low amounts in most vertebrate tissues and can phosphorylate certain proteins. |
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This entity has been manually annotated by the ChEBI Team.
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| ZINC000008218065 |
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Molfile
XML
SDF
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more structures >>
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InChI=1S/C12H19N4O10P3S/c1- 8-11(30-7-16(8)6-10-5-14-9(2)15-12(10)13)3-4-24-28(20,21)26-29(22,23)25-27(17,18)19/h5,7H,3-4,6H2,1-2H3,(H5-,13,14,15,17,18,19,20,21,22,23)/p+1 |
| IWLROWZYZPNOFC-UHFFFAOYSA-O |
| CC1=C(CCOP(O)(=O)OP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=C(N)N=C(C)N=C1 |
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Mus musculus
(NCBI:txid10090)
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Source: BioModels - MODEL1507180067
See:
PubMed
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Rattus norvegicus
(NCBI:txid10116)
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Found in
brain
(BTO:0000142).
See:
PubMed
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Arabidopsis thaliana
(NCBI:txid3702)
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See:
PubMed
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Tricholoma gambosa
(NCBI:txid40144)
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See:
PubMed
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Escherichia coli
(NCBI:txid562)
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See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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See:
PubMed
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Sus scrofa domesticus
(NCBI:txid9825)
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See:
PubMed
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Bronsted base
A molecular entity capable of accepting a hydron from a donor (Bronsted acid).
(via organic amino compound )
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mouse metabolite
Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
Escherichia coli metabolite
Any bacterial metabolite produced during a metabolic reaction in Escherichia coli.
rat metabolite
Any mammalian metabolite produced during a metabolic reaction in rat (Rattus norvegicus).
human metabolite
Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
Arabidopsis thaliana metabolite
Any plant metabolite that is produced by Arabidopsis thaliana.
mammalian metabolite
Any animal metabolite produced during a metabolic reaction in mammals.
fungal metabolite
Any eukaryotic metabolite produced during a metabolic reaction in fungi, the kingdom that includes microorganisms such as the yeasts and moulds.
water-soluble vitamin (role)
Any vitamin that dissolves in water and readily absorbed into tissues for immediate use. Unlike the fat-soluble vitamins, they are not stored in the body and need to be replenished regularly in the diet and will rarely accumulate to toxic levels since they are quickly excreted from the body via urine.
(via B vitamin )
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nutraceutical
A product in capsule, tablet or liquid form that provide essential nutrients, such as a vitamin, an essential mineral, a protein, an herb, or similar nutritional substance.
(via B vitamin )
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View more via ChEBI Ontology
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3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-5-[2-(triphosphooxy)ethyl]-4-methyl-1,3-thiazol-3-ium
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3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-4-methyl-5-(4,6,8,8-trihydroxy-4,6,8-trioxido-3,5,7-trioxa-4,6,8-triphosphaoct-1-yl)-thiazolium
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ChEBI
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3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-5-{2-[(hydroxy{[hydroxy(phosphonooxy)phosphoryl]oxy}phosphoryl)oxy]ethyl}-4-methyl-1,3-thiazol-3-ium
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IUPAC
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thiamin triphosphate
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KEGG COMPOUND
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thiamine triphosphate
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KEGG COMPOUND
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thiamine triphosphoric acid ester
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ChEBI
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ThTP
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ChEBI
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TTP
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ChEBI
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3808304
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Beilstein Registry Number
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Beilstein
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50851-39-3
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CAS Registry Number
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ChEBI
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Gao J, Yang P, Cui Y, Meng Q, Feng Y, Hao Y, Liu J, Piao X, Gu X (2020)
Identification of Metabonomics Changes in Longissimus Dorsi Muscle of Finishing Pigs Following Heat Stress through LC-MS/MS-Based Metabonomics Method.
Animals : an open access journal from MDPI 10, E129 [PubMed:31941143]
[show Abstract]
Heat stress (HS) negatively affects meat quality by affecting material and energy metabolism, and exploring the mechanism underlying the muscle response to chronic HS in finishing pigs is important for the global pork industry. This study investigated changes in the metabolic profiles of the longissimus dorsi (LD) muscle of finishing pigs under high temperature using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS) and multivariate data analysis (MDA). Castrated male DLY pigs (Duroc × Landrance × Yorkshire pigs, n = 24) from 8 litters were divided into three treatment groups: constant optimal ambient temperature at 22 °C and ad libitum feeding (CR, n = 8); constant high ambient temperature at 30 °C and ad libitum feeding (HS, n = 8); and constant optimal ambient temperature 22 °C and pair-feeding to the control pigs (PF, n = 8). The metabolic profile data from LD muscle samples were analyzed by MDA and external search engines. Nine differential metabolites (L-carnosine, acetylcholine, inosinic acid, L-carnitine, L-anserine, L-α-glycerylphosphorylcholine, acetylcarnitine, thiamine triphosphate, and adenosine thiamine diphosphate) were involved in antioxidant function, lipid metabolism, and cell signal transduction, which may decrease post mortem meat quality and play important roles in anti-HS. Four metabolites (L-carnosine, acetylcholine, inosinic acid, and L-carnitine) were verified, and it was indicated that the muscle L-carnitine content was significantly lower in HS than in CR (p < 0.01). The results show that constant HS affects the metabolites in the LD muscle and leads to coordinated changes in the endogenous antioxidant defense and meat quality of finishing pigs. These metabonomics results provide a basis for researching nutritional strategies to reduce the negative effects of heat stress on livestock and present new insights for further research. | Hofmann M, Loubéry S, Fitzpatrick TB (2020)
On the nature of thiamine triphosphate in Arabidopsis.
Plant direct 4, e00258 [PubMed:32885135]
[show Abstract]
Vitamin B1 is a family of molecules, the most renowned member of which is diphosphorylated thiamine (TDP)-a coenzyme vital for the activity of key enzymes of energy metabolism. Triphosphorylated thiamine derivatives also exist within this family, specifically thiamine triphosphate (TTP) and adenosine thiamine triphosphate (ATTP). They have been investigated primarily in mammalian cells and are thought to act as metabolic messengers but have not received much attention in plants. In this study, we set out to examine for the presence of these triphosphorylated thiamine derivatives in Arabidopsis. We could find TTP in Arabidopsis under standard growth conditions, but we could not detect ATTP. Interestingly, TTP is found primarily in shoot tissue. Drivers of TTP synthesis are light intensity, the proton motive force, as well as TDP content. In plants, TTP accumulates in the organellar powerhouses, the plastids, and mitochondria. Furthermore, in contrast to other B1 vitamers, there are strong oscillations in tissue levels of TTP levels over diel periods peaking early during the light period. The elevation of TTP levels during the day appears to be coupled to a photosynthesis-driven process. We propose that TTP may signify TDP sufficiency, particularly in the organellar powerhouses, and discuss our findings in relation to its role. | Muroya S, Oe M, Ojima K (2018)
Thiamine accumulation and thiamine triphosphate decline occur in parallel with ATP exhaustion during postmortem aging of pork muscles.
Meat science 137, 228-234 [PubMed:29223015]
[show Abstract]
We aimed to clarify the mechanisms affecting postmortem thiamine and its phosphoester contents in major edible pork muscles, namely the longissimus lumborum (LL) in addition to vastus intermedius (VI). Metabolomic analysis by capillary electrophoresis-time of flight mass spectrometry revealed that the level of thiamine triphosphate (ThTP), approximately 1.8-fold higher in LL than in VI muscle at 0h postmortem, declined in the first 24hrs, resulting in an undetectable level at 168h postmortem in both muscles. In contrast, the thiamine content in both muscles increased after 24h postmortem during the aging process. The thiamine accumulation and ThTP decline progressed in parallel with a drastic reduction of the ATP level. The intermuscular differences in pH at 24h and in expression of thiamine transporter and thiamine pyrophosphokinase might result in delayed thiamine generation in LL. These results suggest that postmortem ATP exhaustion forced ThTP hydrolysis and further depyrophosphorylation of thiamine diphosphate in the porcine muscles, which resulted in thiamine accumulation. | Martinez J, Truffault V, Hothorn M (2015)
Structural Determinants for Substrate Binding and Catalysis in Triphosphate Tunnel Metalloenzymes.
The Journal of biological chemistry 290, 23348-23360 [PubMed:26221030]
[show Abstract]
Triphosphate tunnel metalloenzymes (TTMs) are present in all kingdoms of life and catalyze diverse enzymatic reactions such as mRNA capping, the cyclization of adenosine triphosphate, the hydrolysis of thiamine triphosphate, and the synthesis and breakdown of inorganic polyphosphates. TTMs have an unusual tunnel domain fold that harbors substrate- and metal co-factor binding sites. It is presently poorly understood how TTMs specifically sense different triphosphate-containing substrates and how catalysis occurs in the tunnel center. Here we describe substrate-bound structures of inorganic polyphosphatases from Arabidopsis and Escherichia coli, which reveal an unorthodox yet conserved mode of triphosphate and metal co-factor binding. We identify two metal binding sites in these enzymes, with one co-factor involved in substrate coordination and the other in catalysis. Structural comparisons with a substrate- and product-bound mammalian thiamine triphosphatase and with previously reported structures of mRNA capping enzymes, adenylate cyclases, and polyphosphate polymerases suggest that directionality of substrate binding defines TTM catalytic activity. Our work provides insight into the evolution and functional diversification of an ancient enzyme family. | Bettendorff L, Lakaye B, Kohn G, Wins P (2014)
Thiamine triphosphate: a ubiquitous molecule in search of a physiological role.
Metabolic brain disease 29, 1069-1082 [PubMed:24590690]
[show Abstract]
Thiamine triphosphate (ThTP) was discovered over 60 years ago and it was long thought to be a specifically neuroactive compound. Its presence in most cell types, from bacteria to mammals, would suggest a more general role but this remains undefined. In contrast to thiamine diphosphate (ThDP), ThTP is not a coenzyme. In E. coli cells, ThTP is transiently produced in response to amino acid starvation, while in mammalian cells, it is constitutively produced at a low rate. Though it was long thought that ThTP was synthesized by a ThDP:ATP phosphotransferase, more recent studies indicate that it can be synthesized by two different enzymes: (1) adenylate kinase 1 in the cytosol and (2) FoF1-ATP synthase in brain mitochondria. Both mechanisms are conserved from bacteria to mammals. Thus ThTP synthesis does not seem to require a specific enzyme. In contrast, its hydrolysis is catalyzed, at least in mammalian tissues, by a very specific cytosolic thiamine triphosphatase (ThTPase), controlling the steady-state cellular concentration of ThTP. In some tissues where adenylate kinase activity is high and ThTPase is absent, ThTP accumulates, reaching ≥ 70% of total thiamine, with no obvious physiological consequences. In some animal tissues, ThTP was able to phosphorylate proteins, and activate a high-conductance anion channel in vitro. These observations raise the possibility that ThTP is part of a still uncharacterized cellular signaling pathway. On the other hand, its synthesis by a chemiosmotic mechanism in mitochondria and respiring bacteria might suggest a role in cellular energetics. | Gigliobianco T, Gangolf M, Lakaye B, Pirson B, von Ballmoos C, Wins P, Bettendorff L (2013)
An alternative role of FoF1-ATP synthase in Escherichia coli: synthesis of thiamine triphosphate.
Scientific reports 3, 1071 [PubMed:23323214]
[show Abstract]
In E. coli, thiamine triphosphate (ThTP), a putative signaling molecule, transiently accumulates in response to amino acid starvation. This accumulation requires the presence of an energy substrate yielding pyruvate. Here we show that in intact bacteria ThTP is synthesized from free thiamine diphosphate (ThDP) and P(i), the reaction being energized by the proton-motive force (Δp) generated by the respiratory chain. ThTP production is suppressed in strains carrying mutations in F(1) or a deletion of the atp operon. Transformation with a plasmid encoding the whole atp operon fully restored ThTP production, highlighting the requirement for F(o)F(1)-ATP synthase in ThTP synthesis. Our results show that, under specific conditions of nutritional downshift, F(o)F(1)-ATP synthase catalyzes the synthesis of ThTP, rather than ATP, through a highly regulated process requiring pyruvate oxidation. Moreover, this chemiosmotic mechanism for ThTP production is conserved from E. coli to mammalian brain mitochondria. | Gangolf M, Wins P, Thiry M, El Moualij B, Bettendorff L (2010)
Thiamine triphosphate synthesis in rat brain occurs in mitochondria and is coupled to the respiratory chain.
The Journal of biological chemistry 285, 583-594 [PubMed:19906644]
[show Abstract]
In animals, thiamine deficiency leads to specific brain lesions, generally attributed to decreased levels of thiamine diphosphate, an essential cofactor in brain energy metabolism. However, another far less abundant derivative, thiamine triphosphate (ThTP), may also have a neuronal function. Here, we show that in the rat brain, ThTP is essentially present and synthesized in mitochondria. In mitochondrial preparations from brain (but not liver), ThTP can be produced from thiamine diphosphate and P(i). This endergonic process is coupled to the oxidation of succinate or NADH through the respiratory chain but cannot be energized by ATP hydrolysis. ThTP synthesis is strongly inhibited by respiratory chain inhibitors, such as myxothiazol and inhibitors of the H(+) channel of F(0)F(1)-ATPase. It is also impaired by disruption of the mitochondria or by depolarization of the inner membrane (by protonophores or valinomycin), indicating that a proton-motive force (Deltap) is required. Collapsing Deltap after ThTP synthesis causes its rapid disappearance, suggesting that both synthesis and hydrolysis are catalyzed by a reversible H(+)-translocating ThTP synthase. The synthesized ThTP can be released from mitochondria in the presence of external P(i). However, ThTP probably does not accumulate in the cytoplasm in vivo, because it is not detected in the cytosolic fraction obtained from a brain homogenate. Our results show for the first time that a high energy triphosphate compound other than ATP can be produced by a chemiosmotic type of mechanism. This might shed a new light on our understanding of the mechanisms of thiamine deficiency-induced brain lesions. | Bettendorff L, Wins P (2009)
Thiamin diphosphate in biological chemistry: new aspects of thiamin metabolism, especially triphosphate derivatives acting other than as cofactors.
The FEBS journal 276, 2917-2925 [PubMed:19490098]
[show Abstract]
Prokaryotes, yeasts and plants synthesize thiamin (vitamin B1) via complex pathways. Animal cells capture the vitamin through specific high-affinity transporters essential for internal thiamin homeostasis. Inside the cells, thiamin is phosphorylated to higher phosphate derivatives. Thiamin diphosphate (ThDP) is the best-known thiamin compound because of its role as an enzymatic cofactor. However, in addition to ThDP, at least three other thiamin phosphates occur naturally in most cells: thiamin monophosphate, thiamin triphosphate (ThTP) and the recently discovered adenosine thiamin triphosphate. It has been suggested that ThTP has a specific neurophysiological role, but recent data favor a much more basic metabolic function. During amino acid starvation, Escherichia coli accumulate ThTP, possibly acting as a signal involved in the adaptation of the bacteria to changing nutritional conditions. In animal cells, ThTP can phosphorylate some proteins, but the physiological significance of this mechanism remains unknown. Adenosine thiamin triphosphate, recently discovered in E. coli, accumulates during carbon starvation and might act as an alarmone. Among the proteins involved in thiamin metabolism, thiamin transporters, thiamin pyrophosphokinase and a soluble 25-kDa thiamin triphosphatase have been characterized at the molecular level, in contrast to thiamin mono- and diphosphatases whose specificities remain to be proven. A soluble enzyme catalyzing the synthesis of adenosine thiamin triphosphate from ThDP and ADP or ATP has been partially characterized in E. coli, but the mechanism of ThTP synthesis remains elusive. The data reviewed here illustrate the complexity of thiamin biochemistry, which is not restricted to the cofactor role of ThDP. | Gigliobianco T, Lakaye B, Makarchikov AF, Wins P, Bettendorff L (2008)
Adenylate kinase-independent thiamine triphosphate accumulation under severe energy stress in Escherichia coli.
BMC microbiology 8, 16 [PubMed:18215312]
[show Abstract]
BackgroundThiamine triphosphate (ThTP) exists in most organisms and might play a role in cellular stress responses. In E. coli, ThTP is accumulated in response to amino acid starvation but the mechanism of its synthesis is still a matter of controversy. It has been suggested that ThTP is synthesized by an ATP-dependent specific thiamine diphosphate kinase. However, it is also known that vertebrate adenylate kinase 1 catalyzes ThTP synthesis at a very low rate and it has been postulated that this enzyme is responsible for ThTP synthesis in vivo.ResultsHere we show that bacterial, as vertebrate adenylate kinases are able to catalyze ThTP synthesis, but at a rate more than 106-fold lower than ATP synthesis. This activity is too low to explain the high rate of ThTP accumulation observed in E. coli during amino acid starvation. Moreover, bacteria from the heat-sensitive CV2 strain accumulate high amounts of ThTP (>50% of total thiamine) at 37 degrees C despite complete inactivation of adenylate kinase and a subsequent drop in cellular ATP.ConclusionThese results clearly demonstrate that adenylate kinase is not responsible for ThTP synthesis in vivo. Furthermore, they show that E. coli accumulate large amounts of ThTP under severe energy stress when ATP levels are very low, an observation not in favor of an ATP-dependent mechanisms for ThTP synthesis. | Lakaye B, Wirtzfeld B, Wins P, Grisar T, Bettendorff L (2004)
Thiamine triphosphate, a new signal required for optimal growth of Escherichia coli during amino acid starvation.
The Journal of biological chemistry 279, 17142-17147 [PubMed:14769791]
[show Abstract]
Thiamine triphosphate (ThTP) is present in low amounts in most organisms from bacteria to humans, but its biological role remains unknown. Escherichia coli grown aerobically in LB medium contain no detectable amounts of ThTP, but when they are transferred to M9 minimal medium with a substrate such as glucose or pyruvate, there is a rapid but transient accumulation of relatively high amounts of ThTP (about 20% of total thiamine). If a mixture of amino acids is present in addition to glucose, ThTP accumulation is impaired, suggesting that the latter may occur in response to amino acid starvation. To test the importance of ThTP for bacterial growth, we used an E. coli strain overexpressing a specific human recombinant thiamine triphosphatase as a glutathione S-transferase (GST) fusion protein (GST-ThTPase). Those bacteria were unable to accumulate measurable amounts of ThTP. On minimal medium supplemented with glucose, pyruvate, or acetate, they exhibited an intermediate plateau in cell growth compared with control bacteria expressing GST alone or a GST fusion protein unrelated to thiamine metabolism. These results suggest that the early accumulation of ThTP initiates a reaction cascade involved in the adaptation of bacteria to stringent conditions such as amino acid starvation. This is the first demonstration of a physiological role of this ubiquitous compound in any organism. | Makarchikov AF, Lakaye B, Gulyai IE, Czerniecki J, Coumans B, Wins P, Grisar T, Bettendorff L (2003)
Thiamine triphosphate and thiamine triphosphatase activities: from bacteria to mammals.
Cellular and molecular life sciences : CMLS 60, 1477-1488 [PubMed:12943234]
[show Abstract]
In most organisms, the main form of thiamine is the coenzyme thiamine diphosphate. Thiamine triphosphate (ThTP) is also found in low amounts in most vertebrate tissues and can phosphorylate certain proteins. Here we show that ThTP exists not only in vertebrates but is present in bacteria, fungi, plants and invertebrates. Unexpectedly, we found that in Escherichia coli as well as in Arabidopsis thaliana, ThTP was synthesized only under particular circumstances such as hypoxia (E. coli) or withering (A. thaliana). In mammalian tissues, ThTP concentrations are regulated by a specific thiamine triphosphatase that we have recently characterized. This enzyme was found only in mammals. In other organisms, ThTP can be hydrolyzed by unspecific phosphohydrolases. The occurrence of ThTP from prokaryotes to mammals suggests that it may have a basic role in cell metabolism or cell signaling. A decreased content may contribute to the symptoms observed during thiamine deficiency. | Makarchikov AF, Wins P, Janssen E, Wieringa B, Grisar T, Bettendorff L (2002)
Adenylate kinase 1 knockout mice have normal thiamine triphosphate levels.
Biochimica et biophysica acta 1592, 117-121 [PubMed:12379473]
[show Abstract]
Thiamine triphosphate (ThTP) is found at low concentrations in most animal tissues and it may act as a phosphate donor for the phosphorylation of proteins, suggesting a potential role in cell signaling. Two mechanisms have been proposed for the enzymatic synthesis of ThTP. A thiamine diphosphate (ThDP) kinase (ThDP+ATP if ThTP+ADP) has been purified from brewer's yeast and shown to exist in rat liver. However, other data suggest that, at least in skeletal muscle, adenylate kinase 1 (AK1) is responsible for ThTP synthesis. In this study, we show that AK1 knockout mice have normal ThTP levels in skeletal muscle, heart, brain, liver and kidney, demonstrating that AK1 is not responsible for ThTP synthesis in those tissues. We predict that the high ThTP content of particular tissues like the Electrophorus electricus electric organ, or pig and chicken skeletal muscle is more tightly correlated with high ThDP kinase activity or low soluble ThTPase activity than with non-stringent substrate specificity and high activity of adenylate kinase. | Shioda T, Kawasaki T (1992)
Thiamin triphosphate does not affect contraction of skinned fibers.
Journal of nutritional science and vitaminology 38, 529-533 [PubMed:1294713]
[show Abstract]
Effects of thiamin triphosphate (TTP) on contraction of chemically skinned fibers prepared from the extensor digitorum longus muscle of guinea pigs were investigated. The addition of TTP at 40 microM concentration affected neither Ca2+ uptake nor Ca(2+)-induced Ca2+ release by sarcoplasmic reticulum. Contraction of myofibril was not affected by TTP either. | Kawasaki T (1992)
Thiamin triphosphate synthesis in animals.
Journal of nutritional science and vitaminology Spec No, 383-386 [PubMed:1297771]
[show Abstract]
All the evidence obtained indicates that the synthesis of TTP in vitro and in vivo is catalyzed by cytosolic adenylate kinase. Further studies should explore whether adenylate kinase is the only enzyme involved in TTP synthesis, together with physiological roles of TTP in living organisms. | Koyama S, Kawasaki T (1992)
[Biosynthesis and possible physiological roles of thiamine triphosphate in animal].
Seikagaku. The Journal of Japanese Biochemical Society 64, 393-397 [PubMed:1506715] | Nishimune T, Hayashi R (1987)
Hydrolysis and synthesis of thiamin triphosphate in bacteria.
Journal of nutritional science and vitaminology 33, 113-127 [PubMed:3039089]
[show Abstract]
Thiamin triphosphate (ThTP) in early stationary phase cells of Escherichia coli grown in nutrient broth with 0.1% yeast extract was found to constitute approximately 5-7% of cellular thiamin diphosphate (ThDP) or around 5 nmol/g cell. Nearly the same level of ThTP was obtained in a Bacillus strain. When E. coli was loaded with an excess of ThTP or ThDP, cellular ThTP was found to be controlled in the course of the long term to maintain its ratio to the amount of cellular ThDP. The ThTP vs. ThDP ratio in E. coli cells after short-term ThDP uptake was found to be a function of the cellular growth phase. The ratio in early exponential phase E. coli cells was found to be approximately 4% and it became lower (less than 3%) when cell growth proceeded to the late exponential stage. Two phosphatases specific for ThTP (ThTPase) among thiamin phosphates were detected in E. coli. One required Mg2+ and was found mainly in the soluble fraction, while the other was Mg2+-independent and originated from the membrane. The two ThTPases were similar to their rat tissue counterparts. | Cooper JR, Nishino K (1986)
Enzymatic synthesis of thiamin triphosphate.
Methods in enzymology 122, 24-29 [PubMed:3010036] | Nishino K (1983)
[Thiamin triphosphate and Leigh's disease].
Rinsho shinkeigaku = Clinical neurology 23, 1097-1099 [PubMed:6329572] |
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