Cyclic ADP-ribose

Cyclic ADP-Ribose

Cyclic ADP-ribose

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Description:
Cyclic ADP Ribose, frequently abbreviated as cADPR, is a cyclic adenine nucleotide (like cAMP) with two phosphate groups present on 5' OH of the adenosine (like ADP), further connected to another ribose at the 5' position, which, in turn, closes the cycle by glycosidic bonding to the nitrogen 1 (N<sup>1</sup>) of the same adenine base (whose position N<sup>9</sup> has the glycosidic bond to the other ribose)-glycosidic bond to adenine is what distinguishes cADPR from ADP-ribose (ADPR), the non-cyclic analog. cADPR is produced from nicotinamide adenine dinucleotide (NAD<sup>+</sup>) by ADP-ribosyl cyclases (EC 3.2.2.5) as part of a second messenger system.

Function

cADPR is a cellular messenger for calcium signaling. It is the physiological allosteric modulator of the ryanodine receptor (RyR), which stimulates calcium-induced calcium release at lower cytosolic concentrations of Ca<sup>2+</sup>. RyR activation with high concentration of caffeine is partly due to caffeine's mimicking the binding of cADPR to RyRs. Whether the action is by direct binding to RyR or indirect (through binding with FKBP12.6) is debated. Some reports suggest that cADPR binding makes FKBP12.6, which normally binds RyR2, to fall off the RYR2.

Metabolism

cADPR and ADPR are synthesized from NAD<sup>+</sup> by the bifunctional ectoenzymes of the...
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