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Long-Chain Acyl-CoA as a Multi-effector Ligand in Cellular Metabolism¹

Departments of Medicine and Nutritional Sciences, University of Wisconsin, Madison, WI 53706

Fatty acyl-CoA esters have the ability to bind at specific sites on certain proteins through their CoA moiety, thereby acting as modulators of cellular metabolism. In some cases at least, the acyl-CoA competes with cofactors (nucleotides) for binding to the proteins and results in either their activation or inhibition of catalytic activity. Photolabeling derivatives of acyl-CoA permit covalent binding of the esters to the proteins, which should lead to determination of amino acid residues required for ligand binding, if a common binding motif exists. On the basis of the accumulation of published results, there is now evidence to implicate acyl-CoA esters in the regulation of a variety of biological processes, ranging from mitochondrial metabolism to gene transcription to insulin secretion and signaling.

KEY WORDS: • acyl CoA • regulatory ligand • metabolism

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