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Thiaminylated adenine nucleotides. Chemical synthesis, structural characterization and natural occurrence
Author(s) -
Frédérich Michel,
Delvaux David,
Gigliobianco Tiziana,
Gangolf Marjorie,
Dive Georges,
Mazzucchelli Gabriel,
Elias Benjamin,
De Pauw Edwin,
Angenot Luc,
Wins Pierre,
Bettendorff Lucien
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07040.x
Subject(s) - thiamine , thiamine pyrophosphate , cofactor , chemistry , biochemistry , adenosine triphosphate , adenosine diphosphate , adenosine , stereochemistry , biology , enzyme , platelet , platelet aggregation , immunology
Thiamine and its three phosphorylated derivatives (mono‐, di‐ and triphosphate) occur naturally in most cells. Recently, we reported the presence of a fourth thiamine derivative, adenosine thiamine triphosphate, produced in Escherichia coli in response to carbon starvation. Here, we show that the chemical synthesis of adenosine thiamine triphosphate leads to another new compound, adenosine thiamine diphosphate, as a side product. The structure of both compounds was confirmed by MS analysis and 1 H‐, 13 C‐ and 31 P‐NMR, and some of their chemical properties were determined. Our results show an upfield shifting of the C‐2 proton of the thiazolium ring in adenosine thiamine derivatives compared with conventional thiamine phosphate derivatives. This modification of the electronic environment of the C‐2 proton might be explained by a through‐space interaction with the adenosine moiety, suggesting U‐shaped folding of adenosine thiamine derivatives. Such a structure in which the C‐2 proton is embedded in a closed conformation can be located using molecular modeling as an energy minimum. In E. coli , adenosine thiamine triphosphate may account for 15% of the total thiamine under energy stress. It is less abundant in eukaryotic organisms, but is consistently found in mammalian tissues and some cell lines. Using HPLC, we show for the first time that adenosine thiamine diphosphate may also occur in small amounts in E. coli and in vertebrate liver. The discovery of two natural thiamine adenine compounds further highlights the complexity and diversity of thiamine biochemistry, which is not restricted to the cofactor role of thiamine diphosphate.