ThTP
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Thiamine triphosphate (ThTP) is a biomolecule found in most organisms including
bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
,
fungi A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...
,
plant Plants are the eukaryotes that form the Kingdom (biology), kingdom Plantae; they are predominantly Photosynthesis, photosynthetic. This means that they obtain their energy from sunlight, using chloroplasts derived from endosymbiosis with c ...
s and
animal Animals are multicellular, eukaryotic organisms in the Biology, biological Kingdom (biology), kingdom Animalia (). With few exceptions, animals heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, ...
s. Chemically, it is the
triphosphate A polyphosphate is a salt or ester of polymeric oxyanions formed from tetrahedral PO4 (phosphate) structural units linked together by sharing oxygen atoms. Polyphosphates can adopt linear or a cyclic (also called, ring) structures. In biology, th ...
derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...
of the vitamin
thiamine Thiamine, also known as thiamin and vitamin B1, is a vitamin – an Nutrient#Micronutrients, essential micronutrient for humans and animals. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosp ...
.


Function

It has been proposed that ThTP has a specific role in nerve excitability, but this has never been confirmed and recent results suggest that ThTP probably plays a role in cell energy metabolism. Low or absent levels of thiamine triphosphate have been found in Leigh's disease. In ''
E. coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escherichia'' that is commonly foun ...
'', ThTP is accumulated in the presence of
glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...
during
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
starvation. On the other hand, suppression of the carbon source leads to the accumulation, of
adenosine thiamine triphosphate 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 starvatio ...
(AThTP).


Metabolism

It has been shown that in brain ThTP is synthesized in mitochondria by a chemiosmotic mechanism, perhaps similar to
ATP synthase ATP synthase is an enzyme that catalyzes the formation of the energy storage molecule adenosine triphosphate (ATP) using adenosine diphosphate (ADP) and inorganic phosphate (Pi). ATP synthase is a molecular machine. The overall reaction catalyzed ...
. In
mammals A mammal () is a vertebrate animal of the class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three middle e ...
, ThTP is hydrolyzed to
thiamine pyrophosphate Thiamine pyrophosphate (TPP or ThPP), or thiamine diphosphate (ThDP), or cocarboxylase is a thiamine (vitamin B1) derivative which is produced by the enzyme thiamine diphosphokinase. Thiamine pyrophosphate is a cofactor that is present in all liv ...
(ThDP) by a specific thiamine-triphosphatase. It can also be converted into ThDP by thiamine-diphosphate kinase.


History

Thiamine triphosphate (ThTP) was chemically synthesized in 1948 at a time when the only organic
triphosphate A polyphosphate is a salt or ester of polymeric oxyanions formed from tetrahedral PO4 (phosphate) structural units linked together by sharing oxygen atoms. Polyphosphates can adopt linear or a cyclic (also called, ring) structures. In biology, th ...
known was ATP. The first claim of the existence of ThTP in living organisms was made in rat liver, followed by baker’s yeast. Its presence was later confirmed in rat tissues and in plants germs, but not in seeds, where thiamine was essentially unphosphorylated. In all those studies, ThTP was separated from other thiamine derivatives using a paper chromatographic method, followed by
oxidation Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...
in fluorescent thiochrome compounds with
ferricyanide Ferricyanide is the name of the anion CN)6sup>3−. It is also called hexacyanoferrate(III) and in rare, but systematic name">systematic nomenclature, hexacyanidoferrate(III). The most common salt of this anion is potassium ferricyanide, a red ...
in
alkaline In chemistry, an alkali (; from the Arabic word , ) is a basic salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as a base that dissolves in water. A solution of a soluble base has a pH greater than 7.0. The ...
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.{{Cite journal , author1=Rindi G. , author2=de Giuseppe L. , name-list-style=amp , year = 1961 , title = A new chromatographic method for the determination of thiamine and its mono-, di- and triphosphates in animal tissues , journal = Biochem. J. , volume = 78 , issue=3 , pages = 602–606 , pmid = 13741738 , pmc = 1205381 , doi=10.1042/bj0780602


References

Biomolecules Organophosphates Thiazoles Thiamine Pyrimidines Phosphate esters