Thiaminylated adenine nucleotides. Chemical synthesis, structural characterization and natural occurrence.
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 1H-, 13C- and 31P-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.
Frédérich
Michel
M
Laboratory of Pharmacognosy, Université de Liège, Belgium.
Delvaux
David
D
Gigliobianco
Tiziana
T
Gangolf
Marjorie
M
Dive
Georges
G
Mazzucchelli
Gabriel
G
Elias
Benjamin
B
De Pauw
Edwin
E
Angenot
Luc
L
Wins
Pierre
P
Bettendorff
Lucien
L
D016475:3T3 Cells; D000225:Adenine / Q000031:analogs & derivatives* / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry; D000244:Adenosine Diphosphate / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry*; D000255:Adenosine Triphosphate / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D001923:Brain Chemistry; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004926:Escherichia coli / Q000737:chemistry; D005347:Fibroblasts / Q000737:chemistry; D006801:Humans; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D018482:Muscle, Skeletal / Q000737:chemistry; D009206:Myocardium / Q000737:chemistry; D011784:Quail; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization; D013835:Thiamine Pyrophosphate / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry* / Q000031:analogs & derivatives; D013838:Thiamine Triphosphate / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry*
C542097:adenine thiamine diphosphate; C519454:adenosine thiamine triphosphate; D013838:Thiamine Triphosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000225:Adenine; D013835:Thiamine Pyrophosphate