Thiaminpyrophosphat

Thiamin pyrophosphate (TPP), also known as thiamine pyrophosphate or thiamin diphosphate, is the biologically active coenzyme form of vitamin B1 (thiamine). It is synthesized in cells from thiamine by the enzyme thiamine pyrophosphokinase, which uses ATP to attach two phosphate groups.

TPP functions as a cofactor for several enzyme complexes that catalyze decarboxylation and transfer reactions in carbohydrate and amino acid metabolism: the pyruvate dehydrogenase complex, the α-ketoglutarate dehydrogenase complex, the branched-chain α-ketoacid dehydrogenase complex, and the transketolase enzyme of the pentose phosphate pathway.

Mechanistically, TPP’s thiazolium ring forms a reactive carbanion (ylide) that stabilizes carbanionic intermediates during decarboxylation and aldehyde transfer, enabling the transfer of two-carbon units to acetyl-CoA or other acceptors in successive steps of metabolism.

Clinical significance: Adequate thiamine intake and metabolism to TPP are essential for energy production. Deficiency, often due to chronic alcohol use, inadequate intake, or malabsorption, can lead to beriberi and Wernicke–Korsakoff syndrome, with symptoms including weakness, neuropathy, ataxia, and mental confusion. Treatment involves thiamine supplementation, with dosing tailored to severity.

Metabolic impact: When TPP-dependent enzymes are impaired, cells accumulate lactate and experience reduced ATP production, reflecting disrupted oxidative decarboxylation and carbohydrate utilization. Genetic or acquired defects affecting TPP availability or utilization can contribute to metabolic disorders, though such cases are relatively uncommon.