Valproate competes with palmitate for binding to serum albumin

Addition of sodium valproate (VPA) to a buffered solution of human serum albumin (HSA) or to serum reduces binding affinity for palmitate. A maximal pharmacologic VPA concentration, 700 microM, added to a 300-microM albumin solution, reduces the reserve albumin concentration for binding of palmitate by a factor of 0.64. One possible site model explaining these findings may be that VPA competes strongly with one among three palmitate molecules, bound to albumin with high affinity, and induces a weaker displacement of a second palmitate.