Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine nucleobase and the other, nicotinamide. NAD exists in two forms: an oxidized and reduced form, abbreviated as NAD and NADH (H for hydrogen), respectively.
In cellular metabolism, NAD is involved in redox reactions, carrying electrons from one reaction to another, so it is found in two forms: NAD is an oxidizing agent, accepting electrons from other molecules and becoming reduced; with H+, this reaction forms NADH, which can be used as a reducing agent to donate electrons. These electron transfer reactions are the main function of NAD. It is also used in other cellular processes, most notably as a substrate of enzymes in adding or removing chemical groups to or from proteins, in posttranslational modifications. Because of the importance of these functions, the enzymes involved in NAD metabolism are targets for drug discovery.
In organisms, NAD can be synthesized from simple building-blocks (de novo) from either tryptophan or aspartic acid, each a case of an amino acid. Alternatively, more complex components of the coenzymes are taken up from nutritive compounds such as niacin; similar compounds are produced by reactions that break down the structure of NAD, providing a salvage pathway that recycles them back into their respective active form.
Some NAD is converted into the coenzyme nicotinamide adenine dinucleotide phosphate (NADP), whose chemistry largely parallels that of NAD, though its predominant role is as a coenzyme in anabolic metabolism.
In the name NAD, the superscripted plus sign indicates the positive formal charge on one of its nitrogen atoms.
Physical and chemical properties
Nicotinamide adenine dinucleotide consists of two nucleosides joined by pyrophosphate. The nucleosides each contain a ribose ring, one with adenine attached to the first carbon atom (the 1' position) (adenosine diphosphate ribose) and the other with nicotinamide at this position.
The compound accepts or donates the equivalent of H−. Such reactions (summarized in formula below) involve the removal of two hydrogen atoms from the reactant (R), in the form of a hydride ion (H−), and a proton (H). The proton is released into solution, while the reductant RH is oxidized and NAD reduced to NADH by transfer of the hydride to the nicotinamide ring.
RH + NAD → NADH + H + R;
From the hydride electron pair, one electron is attracted to the slightly more electronegative atom of the nicotinamide ring of NAD, becoming part of the nicotinamide moiety. The second electron and proton atom are transferred to the carbon atom adjacent to the N atom. The midpoint potential of the NAD/NADH redox pair is −0.32 volts, which makes NADH a moderately strong reducing agent. The reaction is easily reversible, when NADH reduces another molecule and is re-oxidized to NAD. This means the coenzyme can continuously cycle between the NAD and NADH forms without being consumed.
In appearance, all forms of this coenzyme are white amorphous powders that are hygroscopic and highly water-soluble. The solids are stable if stored dry and in the dark. Solutions of NAD are colorless and stable for about a week at 4 °C and neutral pH, but decompose rapidly in acidic or alkaline solutions. Upon decomposition, they form products that are enzyme inhibitors.
Both NAD and NADH strongly absorb ultraviolet light because of the adenine. For example, peak absorption of NAD is at a wavelength of 259 nanometers (nm), with an extinction coefficient of 16,900 M−1cm−1. NADH also absorbs at higher wavelengths, with a second peak in UV absorption at 339 nm with an extinction coefficient of 6,220 M−1cm−1. This difference in the ultraviolet absorption spectra between the oxidized and reduced forms of the coenzymes at higher wavelengths makes it simple to measure the conversion of one to another in enzyme assays – by measuring the amount of UV absorption at 340 nm using a spectrophotometer.