Pyruvate dehydrogenase kinase (PDK) is the primary regulator of flux through the mitochondrial pyruvate dehy-drogenase complex (PDC).Analysis of the primary amino-acid sequences of PDK from various sources reveals that these enzymes include the five domains characteristic of prokaryotic two-component His-kinases, despite the fact that PDKexclusivelyphosphorylates Ser residues in theE1a subunit of the seeming contradiction might be resolved if the PDK-catalyzed reaction employed a phos-pho-His intermediate