malate

Meaning: Malate is the ionized form of malic acid, a four-carbon dicarboxylate intermediate of the citric acid cycle. Fumarase adds water across the double bond of fumarate to give malate. Malate dehydrogenase then oxidizes malate's hydroxyl group to a ketone, forming oxaloacetate and reducing NAD⁺ to NADH. Under standard conditions this oxidation is unfavorable, but it proceeds because citrate synthase keeps the oxaloacetate concentration low.

On the MCAT: Expect questions on cycle order (succinate → fumarate → malate → oxaloacetate) and on counting carriers: one turn yields 3 NADH, 1 FADH₂ and 1 GTP or ATP per acetyl-CoA. Malate also appears in the malate-aspartate shuttle. Cytosolic oxaloacetate is reduced to malate, malate crosses the inner mitochondrial membrane, and it is reoxidized in the matrix. This moves reducing equivalents into the matrix because NADH itself cannot cross. Malate can also carry the carbon skeleton of oxaloacetate out of mitochondria for gluconeogenesis.

Common confusion: Students assign NADH to the fumarate → malate step. That step is a hydration with no redox change, so no carrier is made. FADH₂ forms one step earlier (succinate → fumarate) and NADH forms one step later. Also, the shuttle moves electrons, not NADH molecules.