Control of the citric acid cycle by glyoxylate. 1. A new inhibitor of aconitase formed by the condensation of glyoxylate with oxaloacetate

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Abstract
The rate of the condensation of glyoxylate and oxaloacetate was followed by determining the disappearance of the aldehyde group. The reaction was complete after 3 hr. at 40[degree] and pH 7.4, and did not occur at pH 3. The compound obtained was identified as the trihydrate of the trisodium salt of [alpha]-hydroxy-[beta]-oxalosuccinic acid (oxalomalic acid). A similar compound, but Cg instead of Cg, namely [alpha]-hydroxymethyl-[beta]-oxosuccinic acid, was obtained when formaldehyde was substituted for glyoxylate in the condensation. Only oxalomalate was able to inhibit the activity of crude or purified preparations of aconitase. The inhibitory effect was of the competitive type, with either cis-aconitate or citrate as substrate. A possible physiological role of glyoxylate to control the rate of the citric acid cycle, through the condensation with oxaloacetate, is suggested.