Vitamin B1 and the pyruvate dehydrogenase complex

Abstract Vitamin B1 (thiamine) is converted in living cells into biologically active forms, among which thiamine diphosphate (ThDP) predominates. ThDP is a coenzyme for several key enzymes of carbohydrate metabolism including pyruvate dehydrogenase complex (PDC) which is involved in pyruvate decarboxylation with the acetyl-CoA formation. ThDP-dependent pyruvate dehydrogenase, the first enzyme in the complex, is regulated by phosphorylation–dephosphorylation performed by specific regulatory enzymes. It was shown that ThDP and thiamine triphosphate can participate in this PDC regulation as effectors modulating the activity of the regulatory enzymes. Numerous studies indicate that PDC plays a central role in the maintenance of glucose homeostasis in the body and the disturbance of its regulation can initiate the development of metabolic and neurodegenerative diseases. The search for effectors of the PDC regulatory enzymes, including, among others, thiamine derivatives, is a promising approach to the treatment of the above diseases.