Rahul Sharma (Editor)

Cyclic ADP ribose

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Formula
  
C15H21N5O13P2

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Medical vocabulary what does cyclic adp ribose mean


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 (N1) of the same adenine base (whose position N9 has the glycosidic bond to the other ribose). The N1-glycosidic bond to adenine is what distinguishes cADPR from ADP-ribose (ADPR), the non-cyclic analog. cADPR is produced from nicotinamide adenine dinucleotide (NAD+) by ADP-ribosyl cyclases (EC 3.2.2.5) as part of a second messenger system.

Contents

Medical vocabulary what does cyclic adp ribose mean


Function

cADPR is a cellular messenger for calcium signaling. It stimulates calcium-induced calcium release at lower cytosolic concentrations of Ca2+. Primary target of cADPR is the ER Ca2+ uptake mechanism. Potentiation of Ca2+ release by cADPR is mediated by increased accumulation of Ca2+ in the SR and subsequent luminal Ca2+-dependent activation of ryanodine receptors (RyRs). 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+ by the bifunctional ectoenzymes of the CD38 family (also includes the GPI-anchored CD157 and the specific, monofunctional ADP ribosyl cyclase of the mollusc Aplysia). The same enzymes are also capable of hydrolyzing cADPR to ADPR. Catalysis proceeds via a covalently bound intermediate. The hydrolysis reaction is inhibited by ATP, and cADPR may accumulate. Synthesis and degradation of cADPR by enzymes of the CD38 family involve, respectively, the formation and the hydrolysis of the N1-glycosidic bond. In 2009, the first enzyme able to hydrolyze the phosphoanhydride linkage of cADPR, i.e. the one between the two phosphate groups, has been reported.

References

Cyclic ADP-ribose Wikipedia