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Calcium mobilizing second messengers derived from NAD.

Andreas H Guse1

  • 1The Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.

Biochimica Et Biophysica Acta
|December 24, 2014
PubMed
Summary

Nicotinamide adenine dinucleotide (NAD) is more than a cofactor; its metabolites mobilize calcium ions (Ca²⁺). These NAD metabolites interact with calcium channels, impacting cellular signaling pathways.

Keywords:
ADP-riboseCalcium signalingCofactorCyclic ADP-riboseNAADPNAD

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Area of Science:

  • Biochemistry
  • Cellular Biology
  • Molecular Signaling

Background:

  • Nicotinamide adenine dinucleotide (NAD) traditionally functions as a vital co-factor for oxidoreductase enzymes.
  • Recent research has uncovered novel, non-redox roles for NAD within cellular pathways.
  • NAD metabolism yields key second messengers involved in intracellular calcium regulation.

Purpose of the Study:

  • To review the metabolic pathways of NAD that generate calcium (Ca²⁺)-mobilizing second messengers.
  • To discuss the mechanisms by which these NAD metabolites induce Ca²⁺ release.
  • To explore the potential Ca²⁺ channel targets, including ryanodine receptors and transient receptor potential channels.

Main Methods:

  • Literature review of NAD metabolism and calcium signaling.
  • Analysis of biochemical pathways converting NAD to cyclic ADP-ribose, NAADP, and ADPR.
  • Discussion of experimental evidence implicating specific calcium channels in NAD metabolite signaling.

Main Results:

  • NAD is metabolized into cyclic adenosine diphosphoribose, nicotinic acid adenine dinucleotide phosphate, and adenosine diphosphoribose.
  • These metabolites act as second messengers to mobilize intracellular Ca²⁺ stores.
  • Ryanodine receptors and transient receptor potential channels are identified as putative targets for these NAD-derived messengers.

Conclusions:

  • NAD possesses diverse cellular functions beyond its established role as a redox cofactor.
  • Metabolites of NAD play critical roles in regulating intracellular calcium homeostasis.
  • Understanding these pathways offers insights into cellular signaling and potential therapeutic applications.