Succinate dehydrogenase
The mitochondrial succinate dehydrogenase (SDH or SQR; EC 1.3.5.1) complex (consisting of four nuclearly encoded subunits) catalyses the oxidation of succinate to fumarate in the Krebs (TCA) cycle, and feeds electrons to the respiratory chain (RC) ubiquinone (UQ) pool. Contrasting with most dehydrogenases feeding electrons to the RC, SDH is known to be fully activated upon reduction of the RC and in the presence of ATP, due to dissociation of its physiological inhibitor, oxaloacetate, at the active site[1]. Germline mutations of the genes that encode the SDH subunits result in hereditary paraganglioma-pheochromocytoma syndromes. Patients with such mutations also develop gastrointestinal stromal tumors (GISTs) that can be recognized by their distinctive multinodular architecture, predominantly epithelioid morphology, and predilection for lymph node metastasis[2]. Recently, evidence has been accumulated that SDH is target of the anti Leishmanial drug Sitamaquine (Axon 1515), as it targets the respiratory chain in digitonin-permeabilized promastigotes[3].
[1] P. Rustin et al. Succinate dehydrogenase and human diseases: new insights into a well-known enzyme. Eur J Hum Genet. 2002 May;10(5):289-91.
[2] S.R. Williamson et al. Succinate dehydrogenase-deficient renal cell carcinoma: detailed characterization of 11 tumors defining a unique subtype of renal cell carcinoma. Modern Pathology 2015, 28, 80-94.
[3] L. Carvalho et al. The 8-aminoquinoline analogue sitamaquine causes oxidative stress in Leishmania donovani promastigotes by targeting succinate dehydrogenase. Antimicrob. Agents Chemother. 2011, 55, 4204-4210.
| Axon ID | Name | Description | From price | |
|---|---|---|---|---|
| 1515 | Sitamaquine | Succinate dehydrogenase inhibitor with anti-Leishmanial activity | €120.00 | |