The effect of phosphorylation on pyruvate dehydrogenase

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Abstract
Phosphorylation of the pyruvate dehydrogenase component (E1) of the muscle pyruvate dehydrogenase complex (PDC) by E1‐kinase inhibits substrate conversion both in oxidative and non‐oxidative reactions. Circular dichroism spectra were used to monitor the effect of phosphorylation on the following stages of the process: holoform formation from apo‐E1 and thiamine pyrophosphate (TPP), substrate binding and active site deacetylation. It has been shown that phosphorylation of E1 reduces its affinity for TPP and prevents holo‐E1 interaction with pyruvate. Phosphorylated and dephosphorylated PDC convert 2‐hydroxyethyl‐TPP in similar ways involving half of their active sites; all active sites of E1 function in the presence of deacetylating agents. The data obtained suggest that the phosphorylation and substrate binding sites interact with each other.