Chapter 17: Thiamin

Thiamin (vitamin B1) was the first vitamin characterized and its discovery was at the origin of the concept of vitamin. Thiamin deficiency mainly affects the nervous system and causes two classical diseases, beriberi (a polyneuritic syndrome) and Wernicke-Korsakoff syndrome (anterograde amnesia resulting from brain lesions in alcoholics). Thiamin transport through the membranes of intestinal and other cells requires specific carriers. As the process is rather slow, various lipid-soluble thiamin precursors with better bioavailability have been developed. In the cytosol, thiamin is pyrophosphorylated to thiamin diphosphate (ThDP), an indispenable cofactor in cell energy metabolism. Therefore, thiamin deficiency causes decreased cofactor function, leading to neuronal death. In addition, non-cofactor roles of the triphosphorylated derivatives thiamin triphosphate (ThTP) and adenosine thiamin triphosphate (AThTP) may play a role in metabolic regulation and may contribute to the pathology of thiamin deficiency-induced brain lesions. Current research interests are focused on the metabolism and role of thiamin derivatives (especially in catalysis by ThDP-dependent enzymes) and the biochemical and pathophysiological mechanisms by which thiamin deficiency induces specific brain lesions and may be implicated in other disorders such as Alzheimer’s disease and diabetes.