CHAPTER 5: The Chemistry, Biochemistry and Metabolism of Thiamin (Vitamin B₁)

Thiamin (vitamin B1) is the precursor of several phosphorylated derivatives, the most important being thiamin diphosphate (ThDP), an indispensable coenzyme in cell energy metabolism. The catalytic properties of ThDP can be explained by its ability to form a highly nucleophilic ylide carbanion. During catalysis, this carbanion may attack a carbon adjacent to a carbonyl (>CO) group with the formation of an intermediate acyl carbanion equivalent, which can then be converted and ultimately released. Hence, ThDP is a true catalyst that remains attached to the protein and is regenerated after each reaction cycle. In animals, thiamin deficiency leads to decreased ThDP levels, and as a consequence decreased ThDP-dependent enzyme activities, mainly affecting the nervous system. Other thiamin derivatives that may have specific cell functions are thiamin triphosphate and the recently discovered adenosine thiamin triphosphate or thiaminylated ATP. Both compounds exist in small amounts in prokaryotic and eukaryotic cells, but their roles remain unknown.