Reactivity and inhibitor potential of hydroxycitrate isomers with citrate synthase, citrate lyase, and ATP citrate lyase

Abstract

The four isomers of hydroxycitrate have been tested as substrates and inhibitors for citrate synthase, citrate lyase, and ATP citrate lyase. None of the isomers served as a substrate for citrate synthase and they were moderate to weak inhibitors of this reaction. Of the four isomers, only (pncit)-(2S)-2-hydroxycitrate did not serve as a substrate for citrate lyase while (pncit)-(4S)-4-hydroxycitrate was the only isomer which did not serve as a substrate for ATP citrate lyase. No consistent pattern of reactivity or inhibitor potency was seen with the different isomeric hydroxycitrates. It is proposed that more than one mode of binding is possible between the isomers and the three different active sites.