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Oxaloacetate forms in several ways in nature. A principal route is upon oxidation of L-malate, catalyzed by malate dehydrogenase, in the citric acid cycle. Malate is also oxidized by succinate dehydrogenase in a slow reaction with the initial product being enol-oxaloacetate. [3]
Malate dehydrogenase (EC 1.1.1.37) (MDH) is an enzyme that reversibly catalyzes the oxidation of malate to oxaloacetate using the reduction of NAD + to NADH. This reaction is part of many metabolic pathways, including the citric acid cycle.
Malate oxidase belongs to the family of malate dehydrogenases (EC 1.1.1.37) (MDH) that reversibly catalyze the oxidation of malate to oxaloacetate by means of the reduction of a cofactor. The most common isozymes of malate dehydrogenase use NAD+ or NADP+ as a cofactor to accept electrons and protons. [1]
Malate dehydrogenase, mitochondrial also known as malate dehydrogenase 2 is an enzyme that in humans is encoded by the MDH2 gene. [5]Malate dehydrogenase catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle.
Malate dehydrogenase catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle. The protein encoded by this gene is localized to the cytoplasm and may play pivotal roles in the malate-aspartate shuttle that operates in the metabolic coordination between cytosol and mitochondria.
Oxaloacetate is reduced to malate using NADH, a step required for its transportation out of the mitochondria. Malate is oxidized to oxaloacetate using NAD + in the cytosol, where the remaining steps of gluconeogenesis take place. Oxaloacetate is decarboxylated and then phosphorylated to form phosphoenolpyruvate using the enzyme PEPCK.
After malate reaches the mitochondrial matrix, it is converted by mitochondrial malate dehydrogenase into oxaloacetate, during which NAD + is reduced with two electrons to form NADH. Oxaloacetate is then transformed into aspartate (since oxaloacetate cannot be transported into the cytosol) by mitochondrial aspartate aminotransferase.
For the malate-oxaloacetate shuttle, 4 major genes are involved. They are PMDH1, MDH, PMDH2, mMDH1. [8] PMDH-1 and PMDH-2 encode two different enzymes that provide NAD + for the oxidation of malate. [23] [24] In addition, MDH and mMDH1 encode for an enzyme that directly oxidizes malate. [25] [26]