ADP-ribosyl cyclase and CD38 catalyze the synthesis of a calcium-mobilizing metabolite from NADP

Robert Aarhus, Richard M. Graeff, Deborah M. Dickey, Timothy F. Walseth, Hon Cheung Lee

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Abstract

ADP-ribosyl cyclase catalyzes the cyclization of NAD+ to produce cyclic ADP-ribose (cADPR), which is emerging as an endogenous regulator of the Ca2+-induced Ca2+ release mechanism in cells. CD38 is a lymphocyte differentiation antigen which has recently been shown to be a bifunctional enzyme that can synthesize cADPR from NAD+ as well as hydrolyze cADPR to ADP-ribose. In this study, we Show that both the cyclase and CD38 can also catalyze the exchange of the nicotinamide group of NADP+ with nicotinic acid (NA). The product is nicotinic acid adenine dinucleotide phosphate (NAADP+), a metabolite we have previously shown to be potent in Ca2+ mobilization (Lee, H. C., and Aarhus, R. (1995) J. Biol. Chem. 270, 2152-2157). The switch of the catalysis to the exchange reaction requires acidic pH and NA. The half-maximal effective concentration of NA is about 5 mM for both the cyclase and CD38. In the absence of NA or at neutral pH, the cyclase converts NADP+ to another metabolite, which is identified as cyclic ADP-ribose 2′-phosphate. Under the same conditions, CD38 converts NADP+ to ADP-ribose 2′-phosphate instead, which is the hydrolysis product of cyclic ADP-ribose 2′-phosphate. That two different products of ADP-ribosyl cyclase and CD38, cADPR and NAADP+, are both involved in Ca2+ mobilization suggests a crucial role of these enzymes in Ca2+ signaling.

Original languageEnglish (US)
Pages (from-to)30327-30333
Number of pages7
JournalJournal of Biological Chemistry
Volume270
Issue number51
DOIs
StatePublished - Dec 22 1995

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ADP-ribosyl Cyclase
Cyclic ADP-Ribose
Niacin
Metabolites
NADP
Adenosine Diphosphate Ribose
Calcium
NAD
Niacinamide
Lymphocytes
Cyclization
Differentiation Antigens
Enzymes
Catalysis
Hydrolysis
Ion exchange
Phosphates
Switches
NAADP

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ADP-ribosyl cyclase and CD38 catalyze the synthesis of a calcium-mobilizing metabolite from NADP. / Aarhus, Robert; Graeff, Richard M.; Dickey, Deborah M.; Walseth, Timothy F.; Lee, Hon Cheung.

In: Journal of Biological Chemistry, Vol. 270, No. 51, 22.12.1995, p. 30327-30333.

Research output: Contribution to journalArticle

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