A molecular mechanism for modulating plasma Zn speciation by fatty acids

ABSTRACT: Albumin transports both fatty acids and zinc in plasma. Competitive binding studied by isothermal titration calorimetry revealed that physiologically relevant levels of fatty acids modulate the Zn-binding capacity of albumin, with far-reaching implications for biological zinc speciation. The molecular mechanism for this effect is likely due to a large conformational change elicited by fatty acid binding to a high-affinity interdomain site that disrupts at least one Zn site. Albumin may be a molecular device to “translate ” certain aspects of the organismal energy state into global zinc signals. We present evidence for a fatty-acid-mediated reduction inthe Zn-binding ability of serum albumin. This provides a direct molecular link between fatty acid metabolism and the plasma Zn distribution. A plethora of biological pathways and signaling cascades ar