NAD+ is made of two nucleotides joined through phosphate groups. NMN transforms into NAD+ through the enzymatic activity of NMNAT. NR converts to NMN with the action of an enzyme, NRK. NAD+ biosynthesis in the salvage pathway involves nicotinamide’s conversion to NMN via an enzyme, phosphoribosyltransferase, NMNAT. These compounds include nicotinamide, nicotinic acid, nicotinamide mononucleotide ( NMN), and nicotinamide riboside (NR). The salvage pathway of NAD+ biosynthesis uses naturally occurring compounds related to the vitamin B3. The enzyme, NAD+ synthetase (NADS) then converts NAAD to NAD+. In the second step, the enzyme, NMNAT, converts NAMN to nicotinic acid adenine dinucleotide (NAAD). In the first step, the enzyme NAPRT converts nicotinic acid to nicotinic acid mononucleotide (NAMN). Nicotinic acid converts to NAD+ through three steps. This NAD+ precursor molecule is also produced by the bacterial microflora in the intestines or saliva. Typically, nicotinic acid is found in food but can also be consumed through a dietary supplement. The Preiss-Handler pathway begins with nicotinic acid. The conversion of tryptophan to NAD+ happens in the aqueous part of cells, called cytosol, which is outside of the cellular components (organelles). Along these lines, tryptophan comes from food sources like meat, cheese, eggs, and fish. The kynurenine ( de novo) pathway starts tryptophan, the essential amino acid that you often hear about during Thanksgiving for its association with turkey. The process by which cells generate molecules is called “biosynthesis.” For NAD+, there are three known pathways: the kynurenine ( de novo) pathway, the Preiss-Handler pathway, and the salvage pathway. Here, the red line “a” represents how NAD+ levels change over a lifetime, and the blue where line “b” only takes into account NAD+ level changes post-puberty. As DNA damage and chromosome instability accumulate with age, sirtuins consume more NAD+.Īccording to the plots above, reductions in NAD+ are seen as both men (left) and women (right) age. These proteins, which are linked to healthy aging and longevity, use NAD+ to regulate metabolism, maintain stable chromosomes, and repair damaged DNA. The level of enzymes in our immune system increases as we age, depleting the NAD+ levels in the body.Īnother class of enzymes that use NAD+ are called sirtuins. The more active the immune system is the more NAD+ the enzyme consumes. Out of all these functions that require NAD+, many scientists believe that PARPs contribute the most.Įnzymes in our immune system consume NAD+, too. The depletion of NAD+ through PARP activation during aging appears to contribute to various diseases. By consuming NAD+, PARPs can perform DNA repair functions. The damage to our genetic blueprint activates several proteins, including enzymes called PARPs. According to the plots above, reductions in NAD+ are seen as both men (left) and women (right) age. DNA damage accumulates and snowballs with aging. NAD+ levels drop with agingĪs we age, NAD+ levels fall, suggesting important implications in metabolic function and age-related diseases. Other functions of NAD+ include regulating our circadian rhythm, which controls our body’s sleep/wake cycle. Without sufficient NAD+ levels, our cells wouldn’t be able to generate any energy to survive and carry out their functions. With its molecular counterpart, NADH, this vital molecule participates in various metabolic reactions that generate our cell’s energy. NAD+ works as a shuttle bus, transferring electrons from one molecule to another within cells to carry out all sorts of reactions and processes. NAD+ not only helps convert food to energy but also plays a crucial role in maintaining DNA integrity and ensures proper cell function to protect our bodies from aging and disease. The molecule is a linchpin to the function of the generators of cells - mitochondria. Basically, without NAD+, we would be on the fast track to death. From single-cell organisms like bacteria to sophisticated multicellular ones like primates, NAD+ is one of the most abundant and crucial molecules. NAD+ stands for nicotinamide adenine dinucleotide.
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