About MDH

Malate Dehydrogenase (MDH)

Malate dehydrogenase (EC is a redox family of enzymes that catalyze the oxidation of malate to oxalacetate with the concominant oxidation of NADH to NAD+ and H+ . The enzyme is thermodynamically favorable in the direction of OAA to Malate however in the mitochondria, physiological concentrations of OAA are so low to shift the delta Go' to favor the opposite direction. MDH is found in nearly all cells and in many with more than one isozyme present. In mammalian cells MDH is found in both the cytoplasm (MDH1 gene) and in the mitochondria (MDH2 gene) where the enzyme is involved in the Krebs Cycle, Gluconeogenesis and the Malate Aspartate Shuttle. In plants the enzyme is found in seed glycoxysomes (a specialized type of peroxisome) where MDH is involved in fatty acid metabolism as well as mitochondrial MDH (Citric Acid Cycle) while the cytoplasmic (soluble) isoform is involved in autotrophic carbon dioxide fixation and acid metabolism. Bacterial MDH plays the same role as plants in the TCA cycle and in many bacterial strains the enzyme is involved in electron transfer to modify quinones. While most reports show MDH to be a homodimer of 35,000 daltons for each subunit. There are reports of the enzyme acting as a monomer or even a tetramer.

Enzymatic Structure

The secondary structure of a single subunit contains a 9 beta sheet parallel backbone wrapped by 9 large alpha helices. Near the sodium bound end, 4 small anti-parallel beta sheets and 1 small alpha helix enable a turn in the residue chain(small turn). Opposite the sodium bound ligand, 6 alpha helices point towards a common point, three on each side of the beta sheet backbone. The alpha helices form a small groove for a NAD+ cofactor to attach near the beta sheeting. The structure most nearly resembles an alternating alpha/beta classification. As for the 3D structure, the enzyme forms a sort of crevice for the substrate to bind. (taken from proteopedia Jan 2017)

Mechanism and Active site

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