ADP-ribosyl cyclase and CD38 catalyze the synthesis of a calcium-mobilizing metabolite from NADP(+)
ADP-ribosyl cyclase and CD38 catalyze the synthesis of a calcium-mobilizing metabolite from NADP(+)
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DOI：
10.1074/jbc.270.51.30327
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发表时间：
1995-12-22
影响因子：
4.8
通讯作者：
Lee, HC
中科院分区：
文献类型：
--
作者：
Aarhus, R;Graeff, RM;Lee, HC
adp -核糖基环化酶催化NAD（+）环化产生环状adp -核糖（cADPR），是细胞内Ca2+诱导的Ca2+释放机制的内源性调节剂，CD38是一种淋巴细胞分化抗原，最近被证明是一种双功能酶，可以从NAD（+）合成cADPR，也可以将cADPR水解为adp -核糖。我们发现环化酶和CD38也能催化NADP的烟酰胺基团（+）与烟酸（NA）的交换。产物是烟酸腺嘌呤二核苷酸磷酸（NAADP(+)），一种代谢物，我们之前已经证明在Ca2+动员中是有效的(Lee， H. C., and Aarhus， R. (1995) J. Biol。化学，270,2152 -2157)。催化转换为交换反应需要酸性的pH和NA。NA对环化酶和CD38的半最大有效浓度均为5 mM左右。在没有NA或中性pH下，环化酶将NADP（+）转化为另一种代谢物，即环adp -核糖2'-磷酸。在相同条件下，CD38将NADP（+）转化为环adp -核糖2'-磷酸，这是环adp -核糖2'-磷酸的水解产物。adp -核糖基环化酶和CD38的两种不同产物cADPR和NAADP（+）都参与Ca2+动员，这表明这些酶在Ca2+信号传导中起着至关重要的作用。
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.