Biological functions of thiamine derivatives: Focus on non-coenzyme roles

Thiamine (vitamin B1) is mainly known for its diphosphorylated derivatives (ThDP), an essential coenzyme in energy metabolism. However non-coenzyme roles have been suggested for this vitamin for many years. Such roles have remained hypothetical, but recent data from various sources have shed a new light on this hypothesis. First, the existence of other phosphorylated thiamine derivatives, most prominently thiamine triphosphate (ThTP) and adenosine thiamine triphosphate (AThTP) can reach significant levels in E. coli, respectively during amino acid starvation and energy stress. Though much less is known about these compounds in animals, mammalian cells contain a highly specific soluble thiamine triphosphatase controlling cytosolic ThTP concentrations. Second, there is now growing evidence in favour of the existence of thiamine-binding proteins with specific roles in the nervous system, possibly in the regulation of in neurotransmitter release. Thiamine and some of its synthetic precursors with higher bioavailability have beneficial effects in several models of Alzheimer’s disease and may be beneficial for patients suffering from Alzheimer's or Parkinson's diseases. These effects might be related to non-coenzyme roles of thiamine, possibly involving thiamine-binding proteins.