NAD+

NAD⁺ is a coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is often used as a starting point for inhibitor design, a set of 14 analogs with natural NAD⁺ substrate can weakly inhibit NAD glycohydrolase (NADase) activity of CD38 (2 mM < IC50 < 10 mM) ^[1].

NAD⁺, also called nicotinamide adenine dinucleotide, act as a signaling molecule and a cofactor or substrate for enzymatic activities.

NAD⁺ is an oxidizing agent which accepts electrons from other molecules and reduces to NADH ^[2]. NAD⁺ also plays important roles in the activity of several enzymes such as poly (ADP) – ribose polymerases and cADP – ribose synthases, it can be used by some sirtuins to participate in protein deacetylation mediation, which produce O-acetyl-ADP-ribose and nicotinamide as well as the deacetylated protein ^[3].

Oral NAD+ supplementation has been used to combat simple fatigue as well as such mysterious and energy-sapping disorders as chronic fatigue syndrome and fibromyalgia ^[4].

References:

[1]. Division of Biophysics, et al. NAD Analogs in Aid of Chemical Biology and Medicinal Chemistry. Molecules 2019, 24(22), 4187.

[2]. Houtkooper RH1, Cantó C, Wanders R.J., et al. The secret life of NAD+: An old metabolite controlling new metabolic signaling pathways. Endocr. Rev. 2010, 31(2), 194-223.

[3]. Schwer B, Verdin E. Conserved metabolic regulatory functions of sirtuins. Cell Metab. 2008, 7, 104-112.

[4]. Kussmaul, L. and J. Hirst, The mechanism of superoxide production by NADH: ubiquinone oxidoreductase (complex I) from bovine heart mitochondria. Proc Natl Acad Sci U S A, 2006. 103(20): p. 7607-12.