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 attachment to its cognate proteins to confer biological activity. The major lipoylated proteins are highly conserved enzymes of central metabolism, the pyruvate and alpha-ketoglutarate dehydrogenase complexes. The classical lipoate ligase uses ATP to activate the lipoate carboxyl group followed by attachment of the cofactor to a specific subunit of each dehydrogenase complex, and it was assumed that all lipoate attachment proceeded by this mechanism. However, our previous work indicated that Escherichia coli could form lipoylated proteins in the absence of detectable ATP-dependent ligase activity raising the possibility of a class of enzyme that attaches lipoate to the dehydrogenase complexes by a different mechanism. We now report that E. coli and mitochondria contain 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 direct demonstration of a role for the enigmatic acyl carrier proteins of mitochondria.
Jordan
S W
SW
Department of Microbiology, University of Illinois, Urbana, Illinois 61801, USA.
Cronan
J E
JE
D000213:Acyl Carrier Protein / Q000378:metabolism*; D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D001051:Apoenzymes / Q000378:metabolism; D004789:Enzyme Activation; D004926:Escherichia coli / Q000378:metabolism*; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism; D008322:Mammals; D008928:Mitochondria / Q000378:metabolism*; D009492:Neurospora crassa / Q000378:metabolism; D018532:Pisum sativum / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D008063:Thioctic Acid / Q000378:metabolism*
D000213:Acyl Carrier Protein; D001051:Apoenzymes; D011768:Pyruvate Dehydrogenase Complex; D008063:Thioctic Acid; D007655:Ketoglutarate Dehydrogenase Complex; D000217:Acyltransferases