A NEW METABOLIC LINK - THE ACYL CARRIER PROTEIN OF LIPID-SYNTHESIS DONATES LIPOIC ACID TO THE PYRUVATE-DEHYDROGENASE COMPLEX IN ESCHERICHIA-COLI AND MITOCHONDRIA

Lipoic acid is an essential enzyme cofactor that requires covalent att achment to its cognate proteins to confer biological activity. The maj or lipoylated proteins are highly conserved enzymes of central metabol ism the pyruvate and alpha-ketoglutarate dehydrogenase complexes. The classical lipoate ligase uses ATP to activate the lipoate carboxyl gro up followed by attachment of the cofactor to a specific subunit of eac h dehydrogenase complex, and it was assumed that all lipoate attachmen t proceeded by this mechanism. However, our previous work indicated th at Escherichia coli could form lipoylated proteins in the absence of d etectable ATP-dependent ligase activity raising the possibility of a G lass of enzyme that attaches lipoate to the dehydrogenase complexes by a different mechanism. We now report that E. coli and mitochondria co ntain lipoate transferases that use lipoyl-acyl carrier protein as the lipoate donor. This finding demonstrates a direct link between fatty acid synthesis and lipoate attachment and also provides the first dire ct demonstration of a role for the enigmatic acyl carrier proteins of mitochondria.