Thiamine triphosphate

Thiamine triphosphate (ThTP) is found in most organisms, bacteria, fungi, plants and animals.^[1]

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Function

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]} Moreover some results suggesting that ThTP deficiency is responsible for subacute necrotizing encephalopathy or Leigh's disease have not been confirmed. ^[4]

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).

In mammals, ThTP is hydrolyzed by a specific thiamine triphosphatase.^[5]

History

Thiamine triphosphate (ThTP) was chemically synthesized in 1948 at a time when the only organic triphosphate known was ATP.^[6]

The first claim of the existence of ThTP in living organisms was made in rat liver,^[7] followed by baker’s yeast.^[8]

Its presence was later confirmed in rat tissues^[9] and in plants germs, but not in seeds, where thiamine was essentially unphosphorylated.^[10]

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^[11] and bacteria.^[12]

References

1. ^ ^{a b c} 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. Cell Mol Life Sci 60(7):1477-1488.
2. ^ Matsuda T & Cooper JR. (1981) Thiamine as an integral component of brain synaptosomal membranes. Proc Natl Acad Sci U S A 78(9):5886-5889.
3. ^ ^{a b} 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. J Biol Chem 279(17):17142-17147.
4. ^ Cooper JR, Itokawa Y & Pincus JH. (1969) Thiamine triphosphate deficiency in subacute necrotizing encephalomyelopathy. Science 164(875):74-75.
5. ^ Lakaye B., Makarchikov A.F., Fernandes Antunes A., Zorzi W., Coumans B., De Pauw E., Wins P., Grisar T. & Bettendorff L. (2002) Molecular characterization of a specific thiamine triphosphatase widely distributed in mammalian tissues. J Biol Chem 277: 13771-13777.
6. ^ Velluz et al. 1948
7. ^ Rossi-Fanelli et al. 1952
8. ^ Kiessling 1953
9. ^ Greiling and Kiesow 1958
10. ^ Yusa 1961
11. ^ Rindi and Giuseppe 1961
12. ^ Rossi-Fanelli et al. 1961