title: Thiamin diphosphate in biological chemistry: new aspects of thiamin metabolism, especially triphosphate derivatives acting other than as cofactors.
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.
authors.affiliation: GIGA-Neurosciences, University of Liège, Belgium. L.Bettendorff@ulg.ac.be
authors.forename: Lucien
authors.initials: L
authors.lastname: Bettendorff
authors.forename: Pierre
authors.initials: P
authors.lastname: Wins
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D015394:Molecular Structure; D020675:Peroxisomes / Q000378:metabolism; D013831:Thiamine / Q000737:chemistry* / Q000378:metabolism; D013833:Thiamine Monophosphate / Q000737:chemistry / Q000378:metabolism; D013835:Thiamine Pyrophosphate / Q000737:chemistry* / Q000378:metabolism; D013838:Thiamine Triphosphate / Q000737:chemistry* / Q000378:metabolism
chemical_list: C519454:adenosine thiamine triphosphate; D013838:Thiamine Triphosphate; D013833:Thiamine Monophosphate; D000255:Adenosine Triphosphate; D013835:Thiamine Pyrophosphate; D013831:Thiamine