Nicotinamide adenine dinucleotide represents an important coenzyme in the context of energy metabolism. It is derived from niacin (vitamin B3, nicotinic acid amide). Deficiency of vitamin B3 results in the symptoms of pellagra.
What is nicotinamide adenine dinucleotide?
Nicotinamide adenine dinucleotide is a coenzyme that transfers a hydride ion (H-) as part of energy metabolism. It is present in every cell and especially in mitochondria. Nicotinamide adenine dinucleotide or NAD is always present in the equilibrium NAD+/NADH. Here, NAD+ is the oxidized form and NADH is the reduced form. In oxidation reactions, NAD+ is reduced to NADH by accepting one proton (H+) and two electrons (2e-). Formally, this is the transfer of a hydride ion (H-). NADH is very energetic and transfers its energy to ADP to form ATP. While NAD+ is mostly present in the cytosol, NADH is mainly found in the mitochondria. NAD is composed of two nucleotides. One nucleotide contains the nitrogen base adenine, while in the other nucleotide nicotinamide is glycosidically bound to the sugar. Ribose acts as the sugar. The two nucleotides are linked by the phosphate groups. The ring nitrogen on the nicotinic acid amide residue is positively charged in the oxidized form. This form (NAD+) is lower in energy than the reduced form (NADH) because of the aromatic ring.
Function, action, and roles
Nicotinamide adenine dinucleotide forms the redox couple NAD+/NADH. In this process, the redox potential depends on the ratio of the two components. If the ratio of NAD+/NADH is large, there is a high oxidation capacity. The smaller the ratio, the higher the reduction capacity. Both oxidation reactions and reduction reactions must occur simultaneously in biological systems. However, a single redox couple cannot guarantee this. Therefore, the individual reactions with different redox cofactors take place separately. In the cytosol there is mainly the oxidized form, while in the mitochondria the reduced form predominates. Within this redox system, energy buffering takes place again and again. NAD+ simultaneously absorbs energy with the hydride ion (proton + 2 electrons) for intermediate storage. The energy comes from the degradation of energy-rich substrates such as carbohydrates or fatty acids as part of the respiratory chain. When H- is oxidized and released, the energy is transferred to ADP to form energy-rich ATP. ATP is the most important energy store, which, by releasing its energy while forming ADP back, stimulates either energy-consuming reactions (building up the body’s own substances) or mechanical work (muscle work, movement of internal organs) or the formation of heat in the body. Through its redox potential, the nicotinamide adenine dinucleotide ensures a large number of redox reactions that enable an orderly production of energy within the respiratory chain. The energy is repeatedly stored temporarily and released selectively when needed.
Formation, occurrence, and properties
The biosynthesis of NAD+ occurs from nicotinic acid or nicotinamide (niacin, vitamin B3) as well as from the amino acid tryptophan. Both substances have to be absorbed by the body because they are not formed during metabolism. Tryptophan is an essential amino acid and niacin is a vitamin. If these active substances are missing in the diet, deficiency symptoms occur. The daily requirement of vitamin B3 depends on the energy metabolism of the body. The more energy the body needs, the more niacin must be supplied. Poultry, fish, dairy products, mushrooms and eggs in particular contain a lot of niacin. But vitamin B3 is also found in coffee, peanuts and legumes. Deficiency symptoms rarely occur, however, because the amino acid tryptophan can also form NAD. Tryptophan is also present in sufficient quantities in the aforementioned foods. Nicotinate D-ribonucleotide can be synthesized from both starting materials, which is the starting point for the synthesis of NAD+.
Diseases and disorders
Because nicotinamide adenine dinucleotide plays a central role in energy metabolism, its deficiency leads to serious health disorders. In addition to its function as an intermediate energy store, it participates as coenzyme 1 in more than 100 different enzymatic reactions.Besides its influence on energy production, it also stimulates the synthesis of neurotransmitters dopamine, adrenaline or serotonin. Thus, it has a stimulating effect in stressful situations, nervousness, fatigue. It also strengthens the immune system, liver functions, nervous system and also acts as an antioxidant. Through the formation of neurotransmitters it improves brain functions. The memory performance, concentration and thinking ability become better. Positive experiences have also been made in Parkinson’s disease. Studies have shown that the symptoms improve after NADH administration. Although a deficiency of NAD is rare today, it can occur in the case of extremely unbalanced diets. For example, until the beginning of the twentieth century, a mysterious disease called pellagra occurred, especially in Mexico. With the change of diet to corn, a large part of the Mexican population suffered from concentration and sleep disorders, loss of appetite, irritability, skin changes with dermatitis, diarrhea, depression, and inflammation of the oral and gastrointestinal mucosa. The reason was the widespread supply of corn. In corn, both niacin and tryptophan are present only in small amounts. As a result, the formation of NAD+ was disturbed. After the cause was identified, the diet was changed again. Occasionally, an overdose of vitamin B3 results in a skin vasodilator effect, which is also known as a flush. A drop in blood pressure and dizziness may also occur. These symptoms are the expression of increased energy production by NAD+. However, toxic effects have not been observed even at very high doses.
