MalatDehydrogenase

Malate dehydrogenase (MDH) is an enzyme that catalyzes the interconversion of malate and oxaloacetate using nicotinamide adenine dinucleotide (NAD+) or NADP+ as a cofactor. In most animals and bacteria, the reaction is NAD+-dependent and reversible: malate + NAD+ ↔ oxaloacetate + NADH + H+. The enzyme is found in multiple cellular compartments and exists in several isoforms tuned to different metabolic roles.

In mitochondria, malate dehydrogenase (MDH2) participates in the citric acid cycle, converting malate to oxaloacetate and generating NADH for respiration. In the cytosol, malate dehydrogenase (MDH1) links cytosolic and mitochondrial redox states via the malate–aspartate shuttle and contributes to gluconeogenesis and redox balancing. In plants and some microorganisms, NADP+-dependent forms supplement these roles and operate in plastids or other compartments, supplying reducing equivalents for biosynthesis.

Biochemically, MDH is typically a homodimer that binds NAD+/NADH in a Rossmann-fold domain. The catalytic reaction proceeds via hydride transfer from malate to NAD+, with oxaloacetate released, or in the reverse direction when oxaloacetate is reduced to malate. The direction of net flux depends on cellular NAD+/NADH and oxaloacetate availability.

MDH is highly conserved across life and plays a central role in energy metabolism, the malate–aspartate shuttle, and metabolic network balancing between anaplerosis and cataplerosis. In humans, distinct genes encode cytosolic and mitochondrial isoforms, referred to as MDH1 and MDH2.