NADPH

Nicotinamide Adenine Dinucleotide(NAD), reduced nicotinamide adenine dinucleotide (NADH), nicotinamide adenine dinucleotide phosphate (NADP), and reduced nicotinamide adenine dinucleotide phosphate (NADPH) have been known as classic molecules involving in energy metabolism, reductive biosynthesis, and antioxidation. Structurally NADP is identical to NAD except for the additional 2’ phosphate on the adenosine ribose moieties of NADP. However, NAD (including NAD and NADH) are mainly used by the enzymes that catalyze substrate oxidation, while NADP (including NADP and NADPH) are mainly used by the enzymes that catalyze substrate reduction. Recent studies have indicated pivotal roles of NAD-dependent histone deacetylases (i.e., sirtuins) in aging; b) poly(ADP-ribose) polymerase-1 (PARP-1)—-a major NAD-consuming enzyme—-appears to mediate oxidative cell death under many conditions; c) cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate (NAADP)—-two endogeneous molecules generated from NAD—-are key signaling molecules mobilizing intracellular calcium stores; and d) NADPH oxidase is a major generator of reactive oxygen species (ROS) in both immunological reactions and multiple diseases. NAD may affect gene expression through several pathways. 
NADH mediates the activity of the corepressor carboxyl-terminal binding protein—-a transcriptional factor important for cell cycle regulation, development, and transformation and NADH also modulates the activities of Clock:BMAL1 and NPAS2:BMAL1 that are heterodimeric transcription factors controlling circadian clock-associated gene expression. Selective inhibition of NAD synthesis has been shown to induce apoptosis of tumor cells. Because PARP-1 plays critical roles in regulating DNA repair, genomic stability, and cell cycle progression, many studies have been conducted to determine the roles of PARP-1 in carcinogenesis. Because NAD and NADP can profoundly affect cell death and various biological processes including gene expression and signal transduction, future studies may further elucidate important roles of NAD and NADP in carcinogenesis and cancer treatment.