The Inhibition of the Activity of Apple Mitochondria by Oxaloacetate

Abstract

The inhibitory effect of oxaloacetate (OAA) on the activity of mitochondria isolated from the peel of Cox's Orange Pippin apples has been investigated. A given concentration of OAA causes a longer inhibition of succinate than of malate oxidation and the rate of disappearance of OAA is faster in the presence of malate than in that of succinate. Mg⁺⁺⁺, Al⁺⁺⁺, ATP, and glutamate accelerate the disappearance of inhibition by OAA; Ca⁺⁺ reinforces the inhibition. It is established, by estimation of the oxo acids in the reaction mixtures, that the relief from inhibition is directly due to removal of OAA. The fall in rate of O₂ uptake with time, using succinate or malate as substrate, is accompanied by an accumulation of OAA, and the inhibition of succinate oxidation by malate is due to the increased OAA production when malate is oxidized. Some OAA is broken down non-enzymically to form pyruvate and the rate of breakdown is enhanced by Mg⁺⁺; some is metabolized via the Krebs cycle; some disappear in a coupled reaction between pyruvic and malic dehydrogenases to form citrate and malate, and some can be removed by transamination. It is suggested that all these may be factors in a regulatory action of OAA on the operation of the Krebs cycle. It is relevant in this connexion that very small amounts of OAA inhibit the activity of the Krebs cycle when they are produced at the active sites within the mitochondrion.