A Novel ADP-Ribosyl Cyclase (ARC) Regulators

Zainab N Al-Abady, Israa Najm Abdullah Al-Ibadi, Oraas Adnan Hatem, Nawal Khinteel Jabbar, Makarim Ali Enad

Abstract


CD38, which is the main NADase enzyme with its ADP-ribose cyclase (ARC) activity, has been proposed to be involved in many human diseases. Therefore, regulating its activity is the main target of this research. This study proposed four novel regulators; nicotinamide, nicotinic acid, gallic acid, and benzamide, these regulators have a remarkable effect on the cyclase activity of ARC. The cyclase activity of ARC was measured using fluorimetric assay, the reaction was initiated with the addition of enzyme to its substrate nicotinamide guanine dinucleotide (NGD) and the production of cyclic GDP-ribose (cGDPR) was measured with different concentrations from proposed activators. The rate of ADP-ribosyl cyclase activity was increased with the addition of low concentrations of Nicotinamide and Nicotinic acid. However, Nicotinamide and Nicotinic acid are known as ARC inhibitors at high concentrations. The increase of ARC activity was also observed with Gallic acid; it is clear that Gallic acid has a strong effect on the activation of ARC and the formation of cGDPR. The last product was Benzamide, these data reflected the activation effect on ARC. Finally, the search for new ADP-ribosyl cyclase activators and the determination of their roles might provide a new therapeutic strategy for several metabolic and inflammatory conditions.

Keywords


ARC, A novel regulators, cGDPR, NGD.

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DOI: https://doi.org/10.25258/ijddt.v9i4.21

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