Succinate is the anionic form of succinic acid found in the body, and it is a compound generated as part of the Krebs cycle. Succinate is involved in ATP production as a part of the Krebs cycle, and can also be important in extracellular signaling when it binds to the G-protein coupled receptor GPR91, also known as the succinate receptor 1. When succinic acid binds to the succinate receptor 1 and activates it, an activating signal is sent to 1-phosphatidylinositol 4,5-bisohosphate phosphodiesterase beta-1 (PLCB1). This enzyme cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,3,4-triphosphate (IP3) and diacylglycerol (DG). IP3 then activates an IP3 sensitive calcium channel, increasing the concentration of intracellular calcium. This then activates nitric oxide synthase, producing nitric oxide in the cell. It also activates mitogen-activated protein kinase 11 (MAPK11), which in turn activates the cyclic AMP-responsive element-binding protein 1 (CREB1), which stimulates the transcription of DNA. The increased calcium levels can also activate prostaglandin G/H synthase 1 which synthesizes prostaglandins, hormone-like compounds with vasodilating effects that are present in the inflammatory response. DG also serves as an activator in this pathway, activating protein kinase C alpha type. This activates mitogen-activated protein kinases 1 and 3 (MAPK1 and MAPK3), which then lead to the production of prostaglandin E2, as well as the activation of prostaglandin G/H synthase 1. Protein kinase C alpha type can also activate the NF-kappa-B essential modulator, releasing the nuclear factor NF-kappa-B p105 subunit, which then makes its way into the nucleus, where it stimulates transcription of DNA necessary for the inflammatory response.

Succinate Signalling During Inflammation References