Malate dehydrogenase 1 and 2 are enzymes that catalyze the reversible conversion of malate and NAD+ to oxaloacetate and NADH. The mitochondrial isoform (MDH2) plays a major metabolic role in the Krebs Cycle. Current chemotherapies, such as doxorubicin and docetaxel, have side effects such as resistance to the drug or heart failure which have revealed to be at least partially caused by the overexpression of MDH2. In order to address these side effects, current research looks at the effects of inhibitors on malate dehydrogenase; however, studies have yet to address how these inhibitors affect the cytoplasmic isoform (MDH1). This research kinetically characterizes both isoforms of human malate dehydrogenase and compares the inhibition of these two enzymes by mebendazole and visnagin. The Km and kcat values were recorded for both enzymes with and without inhibitors. The aim is to study the inhibition of both enzymes and create a system to find inhibitors that are more effective at inhibiting MDH2.

Kinetic characterization and chemotherapeutic relevant inhibition of human malate dehydrogenase 1 and 2

251st National Meeting (2016)

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