Citric Acid Cycle Intermediates GPCR Family Subtypes and Products

What Are Citric Acid Cycle Intermediates Receptors?

The citric acid cycle intermediates receptor family contains both succinate and oxoglutarate receptors, known as GPR91 and GPR99 respectively. In 2004, the endogenous ligand for GPR91 was discovered. Since then, GPR91 has undergone research to identify its role in inflammation, retinal angiogenesis, and renin production. The oxoglutarate receptor is found in tissues such as the trachea, salivary glands, and nasal mucosa, playing a large role in allergic reactions. Antagonists for GPR99 can be used for the treatment of asthma, allergic rhinitis, bronchoconstriction, primary dysmenorrhoea, and urticaria.

Citric Acid Cycle Intermediates Receptor Information

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GPR91, also known as SUCNR1, is a G Protein-Coupled Receptor with 339 amino acids. It has been characterized as a receptor for Succinate, a citric acid cycle intermediate. Succinate plays a key role in energy metabolism. Local interstitial accumulation of Succinate has recently been reported to serve as an indicator of ischemic or diabetic organ damage in the brain, liver, and kidney. In diabetes patients, the accumulation of Succinate is detectable in the plasma, and more significantly in the renal tubular fluid and urine. It is therefore considered a potential new biomarker of local tissue damage. It has also been shown that Succinate increases blood pressure in animals. The Succinate-induced hypertensive effect involves the renin-angiotensin system that is shown to be absent in GPR91-deficient mice. There is a possible role for GPR91 in renovascular hypertension, a disease closely linked to atherosclerosis, diabetes and renal failure. In a recombinant system overexpressing GPR91, Succinate was shown to not only stimulate calcium mobilization and inositol phosphate (IP) accumulation through the stimulation of Gαq pathway but also to activate the Erk1/2 MAPK pathway and inhibit forskolin-stimulated cAMP accumulation through Gαi pathway.

Human GPR99 also known as GPR80 is a G protein-coupled receptor with 337 amino acids. The mRNA of GPR99 was shown to be expressed predominantly in the kidney. Phylogenetic analysis groups GPR99 into the P2Y subfamily of GPCRs. However, deorphanization studies show that it is a close a relative of GPR91 and have proposed the citric acid cycle intermediate α-Ketoglutarate as a ligand for GPR99 receptor. The receptor couples to Gq upon ligand binding, promoting intracellular calcium increase and inositol phosphate accumulation.

Citric Acid Cycle Intermediates Cell Lines

Receptor FamilyReceptorSpeciesParentalStable Cell Lines Division-Arrested Cells Membranes
Citric Acid Cycle IntermediatesGPR91humanCHO-K1C1144-1DC1144-1MC1144-1
GPR91humanCHO-K1 B-Arrestin2CA1141BA2-1DCA1141BA2-1MCA1141BA2-1