Malate dehydrogenase is specifically activated by citrate in the NAD⁺ ---> NADH (malate ---> oxaloacetate) direction and inhibited by citrate in the NADH ---> NAD⁺ (oxaloacetate ---> malate) direction. Citrate doesn't bind at the enzymes catalytic site but instead binds at a secondary or regulatory site. Citrate influences the equilibrium between two conformations of the enzyme. NAD⁺ and NADH each bind to a particular conformation of the enzyme, with citrate only binding to the conformation of the enzyme that also binds NAD⁺.

Glutamate inhibits production of oxaloacetate by malate dehydrogenase; however, Aspartate aminotransferase can associate with alpha-ketogluterate dehydrogenase complex. This binary complex can associate with the malate dehydrogenase dimer and form a ternary complex. This enables the reverse inhibition of malate oxidation by glutamate. The glutamate reacts with the aminotransferase in the ternary complex without inhibiting malate dehydrogenase. The formation of this ternary complex enhances malate dehydrogenase activity due to a decrease in the K_m of malate.

INTRODUCTION

STRUCTURE

MECHANISM

REGULATION

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