Nicotinamide adenine dinucleotide is a critical coenzyme found in living cells. It is made up of two nucleotides: adenine, a purine base, and nicotinamide, a modified pyrimidine base. The two nucleotides are connected to each other through a bond between the two phosphate groups. The term NADH refers to the chargeless hydrogenated form, while NAD(+) refers to the positively charged coenzyme, Both are fairly polar molecules.
NAD(+) and the phosphorylated form NADP(+) are synthesized through the conversion of dietary niacin, vitamin B3. This is a multienzyme process that uses up two high-energy ATP molecules. If there is insufficient dietary niacin available, the amino acid tryptophan can be converted to nicotinate mononucleotide, one of the intermediates in the niacin conversion pathway. Prolonged terms of insufficient niacin intake can result in a disease called pellagra, which has symptoms of diarrhea and dementia. Plants and microscopic organisms can produce the niacin required to synthesize NAD(+) and NADP(+).
The first function of NAD(+) as a coenzyme involves oxidation-reduction (redox) reactions, in which a substrate loses or gains electrons. The enzymes responsible for redox reactions require a high-energy electron carrier for transfer purposes, and NAD(+) fills that role. The addition of two electrons and a hydrogen atom convert NAD(+) into NADH. During a reaction in which a substrate gains electrons, NADH loses its hydrogen atom and two stored electrons and reverts back to NAD(+).
During glycolysis and the citric acid cycle, NAD(+) is converted to NADH through the oxidation of glucose throughout both processes. NADH produced in this way can pass its two electrons to the mitochondrial electron transport chain. The electrons are passed between three large protein complexes; the third passes them along to oxygen and hydrogen to produce water. Along the way, the transfer of electrons drives the synthesis of ATP, which provides the cell with short-term energy to drive reactions.
Energy stored in the form of lipids is converted to a more usable form by beta-oxidation of fatty acids. NAD(+) and FAD(+), another electron-carrying cofactor, are converted to NADH and FADH(2), respectively, during the oxidation process. The reduced cofactors can then pass electrons into the electron transport chain to produce usable ATP.