Allosteric Regulation
Because malate dehydrogenase is closely tied to the citric acid cycle, regulation is highly dependent on TCA products. High malate concentrations stimulate MDH activity, and, in a converse manner, high oxaloacetate concentrations inhibit the enzyme. Citrate can both allosterically activate and inhibit the enzymatic activity of MDH. It inhibits the oxidation of malate when there are low levels of malate and NAD+. However, in the presence of high levels of malate and NAD+, citrate can stimulate the production of oxaloacetate. It is believed that there is an allosteric regulatory site on the enzyme where citrate can bind to and drive the reaction equilibrium in either direction.
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