Nad Definition and Example

The main role of NAD+ in metabolism is the transfer of electrons from one molecule to another. Reactions of this type are catalyzed by a large group of enzymes called oxidoreductases. The correct names of these enzymes include the names of their two substrates: For example, ubiquinone oxidoreductase NADH catalyzes the oxidation of NADH by coenzyme Q.[47] However, these enzymes are also called dehydrogenases or reductases, with NADH ubiquinone oxidoreductase being commonly referred to as NADH dehydrogenase or sometimes coenzyme Q reductase. [48] Given that many oxidoreductases use NAD+ and NADH as substrates and bind them to a highly conserved structural motif, the idea that NAD+-based inhibitors may be enzyme-specific is surprising. [98] However, this may be possible: inhibitors based on mycophenolic acid and tiazofurin inhibit IMP dehydrogenase at the NAD+ binding site. Because of the importance of this enzyme in purine metabolism, these compounds may be useful as anticancer, antiviral, or immunosuppressive drugs. [98] [99] Other drugs are not enzyme inhibitors, but activate enzymes involved in NAD+ metabolism. Sirtuins are a particularly attractive target for these drugs, as activation of these NAD-dependent deacetylases extends lifespan in some animal models. [100] Compounds such as resveratrol increase the activity of these enzymes, which may be important for their ability to delay aging in model vertebrates[101] and invertebrates. [102] [103] In one experiment, mice given NAD for a week improved mitochrondrial nuclear communication. [104] An example of a NAD-binding bacterial enzyme that is involved in amino acid metabolism and does not have the Rossmann fold is found in Pseudomonas syringae pv. Tomato (PDB: 2CWH; InterPro: IPR003767). [52] A substance, such as a coenzyme or metal ion, that acts with an enzyme and is essential for its activity.

Several clinical trials support the use of NR and NMN. For example, our own clinical study, published in Nature Partner Journals: Aging and Mechanisms of Disease, showed that the base increases NAD+ in whole blood by up to 40%. A Japanese study published in Frontiers in Nutrition found that giving adults 250 mg of NMN per day also increased their NAD+ levels by about 40%. In both cases, the results were obtained safely (i.e. without adverse events) and maintained for the duration of the studies – eight weeks for the base medicine and 12 weeks for NMN. Interestingly, the NMN study also showed that NAD+ levels returned to pre-supplementation levels after supplementation was stopped. Due to the different metabolic pathways of NAD+ biosynthesis between organisms, for example between bacteria and humans, this metabolic zone is a promising area for the development of new antibiotics. [105] [106] For example, the enzyme nicotinamidase, which converts nicotinamide to nicotinic acid, is a target for drug design because this enzyme is absent in humans, but is present in yeast and bacteria. [40] Coenzyme NAD+ is also consumed in ADP-ribose transfer reactions.

For example, niacin, a precursor to NAD+, played a role in mitigating pellagra, a deadly disease that plagued the southern United States in the 1900s. Scientists at the time identified that milk and yeast, both containing NAD+ precursors, relieved symptoms. Over time, scientists have identified several precursors to NAD+, including nicotinic acid, nicotinamide and nicotinamide riboside, which use natural pathways to NAD+.