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First, in the cytosol, VPA is activated and links with reduced acetyl coenzyme A (CoA-SH) to form valproyl-CoA (by the ATP-dependent medium-chain acyl-CoA synthetase, located on the outer side of the mitochondrial membrane)

Robinson P, Sparrow AJ, Psaras Y, Steeples V, Simon JN, Broyles CN, Chang YF, Brook FA, Wang YJ, Blease A, Zhang X, Abassi YA, Geeves MA, Toepfer CN, Watkins H, Redwood C, Daniels MJ