Succinate dehydrogenase and related flavoprotein dehydrogenases (SDH)

Succinate dehydrogenase (SDH) and related flavoprotein dehydrogenases constitute a group of enzymes that utilize flavin adenine dinucleotide (FAD) to catalyze critical redox reactions within the mitochondria. The primary member, SDH (Complex II), is a four-subunit complex that bridges the citric acid cycle and the electron transport chain by oxidizing succinate to fumarate and reducing ubiquinone (UniProt: P31040). Related enzymes in this class, such as electron transfer flavoprotein-ubiquinone oxidoreductase (ETFDH), are essential for fatty acid and amino acid metabolism (NCBI Gene: 2108). Mutations in these enzymes are associated with severe metabolic disorders, such as glutaric acidemia type II, and various hereditary cancer syndromes like paraganglioma, often driven by the accumulation of succinate which acts as an oncometabolite (PubMed: 28611100). While these enzymes are well-established targets for agricultural fungicides (SDHIs), they are increasingly investigated in human medicine as therapeutic targets for metabolic diseases and specific oncology subtypes (PubChem: Succinate Dehydrogenase Inhibitors). Pharmacological modulation of these targets typically aims to disrupt mitochondrial respiration or metabolic flux to treat hyperproliferative or metabolic conditions.

Other names

Complex IISuccinate-ubiquinone oxidoreductaseSQRSuccinate:ubiquinone reductaseFlavoprotein dehydrogenase familySuccinate dehydrogenase complex

Inhibition of the succinate-ubiquinone oxidoreductase activity, preventing the transfer of electrons from succinate to the mitochondrial respiratory chain and disrupting the tricarboxylic acid cycle.