succinate dehydrogenase
Summary
Succinate dehydrogenase is a key enzyme in both the citric acid cycle and electron transport chain, converting succinate to fumarate while reducing FAD to FADH2. It is unique as the only enzyme that participates in both processes and is directly embedded in the inner mitochondrial membrane as Complex II.
Detail
Succinate dehydrogenase (SDH) is a heterotetrameric enzyme complex consisting of four subunits (SDHA, SDHB, SDHC, SDHD) that catalyzes the oxidation of succinate to fumarate in the citric acid cycle while simultaneously reducing FAD to FADH2. As Complex II of the electron transport chain, it transfers electrons from FADH2 to coenzyme Q (ubiquinone), though it does not pump protons across the inner mitochondrial membrane. SDH is the only enzyme that functions in both the TCA cycle and electron transport chain. Clinically, SDH mutations are associated with hereditary paraganglioma-pheochromocytoma syndromes, renal cell carcinoma, and gastrointestinal stromal tumors (GISTs). SDH deficiency leads to succinate accumulation, which acts as an oncometabolite by inhibiting α-ketoglutarate-dependent dioxygenases, including prolyl hydroxylases that regulate HIF-1α, leading to pseudohypoxic conditions that promote tumorigenesis. The enzyme contains iron-sulfur clusters and a covalently bound FAD cofactor, making it essential for cellular respiration and energy production.
Sources
- Lippincott's Illustrated Reviews: Biochemistry
- Robbins and Cotran Pathologic Basis of Disease
- First Aid for the USMLE Step 1
- Harper's Illustrated Biochemistry
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