Thiamine pyrophosphokinase 1 (TPK1) (TPK1)

Thiamine pyrophosphokinase 1 (TPK1) is a cytosolic enzyme that plays a pivotal role in human metabolism by catalyzing the transfer of a pyrophosphate group from ATP to thiamine (vitamin B1), forming thiamine pyrophosphate (TPP) (UniProt Q9H3S4; PubMed 11133214). TPP serves as an indispensable cofactor for several multi-enzyme complexes involved in carbohydrate and amino acid metabolism, such as pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase (NCBI Gene 27010; PubMed 22305526). Consequently, TPK1 activity is essential for maintaining cellular energy homeostasis, particularly in high-demand tissues like the brain and heart (PubMed 22305526). Genetic mutations in TPK1 are linked to thiamine metabolism dysfunction syndrome 5, which manifests as severe neurological impairment and lactic acidosis (OMIM 614458). From a pharmacological perspective, TPK1 is targeted through substrate supplementation with thiamine or its derivatives to treat metabolic deficiencies (PubMed 22305526). Additionally, certain antimetabolites like pyrithiamine act as inhibitors of TPK1, often used in research to model thiamine deficiency (PubMed 11133214).

Other names

Thiamine pyrophosphokinaseThiamine kinasehTPK1TPKThiamine diphosphokinase

Substrate supplementation to increase thiamine pyrophosphate levels or competitive inhibition of thiamine phosphorylation.