Nicotinamide mononucleotide (“NMN” and “β-NMN”) is a nucleotide derived from ribose and nicotinamide. Like nicotinamide riboside, NMN is a derivative of niacin, and humans have enzymes that can use NMN to generate nicotinamide adenine dinucleotide (NADH). NMN may improve adult human metabolism, rendering it more like that of someone ten or twenty years younger.
What is Nicotinamide mononucleotide ("NMN" and "β-NMN")?
Nicotinamide mononucleotide ("NMN" and "β-NMN") is a precursor molecule for the biosynthesis of nicotinamide adenine dinucleotide, or NAD+, a coenzyme that participates in the production of cellular energy and DNA repair.
NMN stands for nicotinamide mononucleotide, a molecule naturally occurring in all life forms. At the molecular level, it is a ribo-nucleotide, which is a basic structural unit of the nucleic acid RNA. Nicotinamide mononucleotide is present in various types of food, including broccoli, avocado, and beef, but it is also an intermediate compound in the NAD+ salvage pathway, the recycling of nicotinamide into NAD+.
What is Nicotinamide Adenine Dinucleotide (NAD+)?
NAD+ is an essential coenzyme required for life and cellular functions. Enzymes are catalysts that make biochemical reactions possible. Coenzymes are ‘helper’ molecules that enzymes need in order to function.
NAD+, a co-enzyme involved in a great deal of biochemical reactions, has been found to be a network node of diverse biological processes. In mammalian cells, NAD+ is synthetized, predominantly through NMN, to replenish the consumption by NADase participating in physiologic processes including DNA repair, metabolism, and cell death. Correspondingly, aberrant NAD+ metabolism is observed in many diseases.
NAD+ can also be synthesized from other precursors including nicotinamide (NAM, also called niacinamide), nicotinic acid (NA), and nicotinamide riboside (NR), which are often collectively referred to as niacin (vitamin B3) or niacin equivalents. These precursors are not equally allocated throughout the body; rather, they exhibit preferential distribution among the blood, brain, gut, and other organs. Tryptophan, an amino acid obtained from the diet, can also be converted into NAD+.
What Does NAD+ Do?
NAD+ is the most abundant molecule in the body besides water, and without it, an organism would die. NAD+ is used by many proteins throughout the body, such as the sirtuins, which repair damaged DNA. It is also important for mitochondria, which are the powerhouses of the cell and generate the chemical energy that our bodies use.
NAD+ acts as a cellular "sensor" to mediate energy-generating pathways and activate NAD+-consuming enzymes such as sirtuins and poly ADP-ribose polymerases (PARP). NAD+ depletion, which occurs with age, has been implicated in the progression of multiple age-related conditions such as metabolic dysregulation and neurodegenerative diseases. Nicotinamide mononucleotide, as well as other precursors such as NR, help maintain cellular levels of NAD+. Boosting NAD+ levels through precursors has proven to have therapeutic potential in treating aging and age-related diseases across multiple animal models.
NAD+ Functions as a Coenzyme in Mitochondria
NAD+ plays an especially active role in metabolic processes, such as glycolysis, the TCA Cycle (AKA Krebs Cycle or Citric Acid cycle), and the electron transport chain, which occurs in our mitochondria and is how we obtain cellular energy.
In its role as a ligand, NAD+ binds to enzymes and transfers electrons between molecules. Electrons are the atomic basis for cellular energy and by transferring them from one molecule to the next, NAD+ acts through a cellular mechanism similar to recharging a battery. A battery is depleted when electrons are expended to provide energy. Those electrons can’t return to their starting point without a boost. In cells, NAD+ serves as that booster. In this way, NAD+ can decrease or increase enzyme activity, gene expression, and cell signaling.
NAD+ Helps Control DNA Damage
As organisms grow older, they accrue DNA damage due to environmental factors such as radiation, pollution, and imprecise DNA replication. According to the current aging theory, the accumulation of DNA damage is the main cause of aging. Almost all cells contain the ‘molecular machinery’ to repair this damage. This machinery consumes NAD+ and energy molecules. Therefore, excessive DNA damage can drain valuable cellular resources.
One important DNA repair protein, PARP (Poly (ADP-ribose) polymerase), depends on NAD+ to function. Older individuals experience decreased levels of NAD+. The accumulation of DNA damage as a result of the normal aging process leads to increased PARP, which causes decreased NAD+ concentration. This depletion is exacerbated by any further DNA damage in the mitochondria.
NMN, β-NMN, Nicotinamide ribonucleoside 5′-phosphate, Nicotinamide D-ribonucleotide, β-Nicotinamide ribose monophosphate, Nicotinamide nucleotide
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