The expression of pyruvate dehydrogenase kinases (PDKs) is induced in starvation, diabetes and cancer. Of the four human PDKs, PDK2 is the most ubiquitously expressed kinase and is most susceptible to inhibition by the drug dichloroacetate (DCA), an acid salt analogue of acetic acid. DCA binds to a hydrophobic pocket in the N-terminal domain of PDK2 and, in the presence of ADP, disrupts the binding of the kinase to the lipoyl (E2) domain of the pyruvate dehydrogenase complex and thus inhibits aberrant PDK activity (Klyuyeva et al. 2007, Li et al. 2009, Roche et al. 2001, James et al. 2017).
Tuganova, A, Klyuyeva, A, Popov, KM
Li, J, Chuang, DT, Kato, M
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