NADsyntetisaatioon

NADsyntetisaatioon refers to the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a vital coenzyme in cellular metabolism and signaling. NAD+ participates in redox reactions by cycling between oxidized (NAD+) and reduced (NADH) states, thereby facilitating energy production, DNA repair, and regulation of gene expression. The maintenance of NAD+ levels is crucial for cell viability, aging processes, and resistance to stress.

Three primary metabolic routes generate NAD+ in mammals. The de novo pathway starts with the essential amino acid tryptophan, which is converted through a series of enzymatic steps into quinolinic acid and then into nicotinic acid mononucleotide (NaMN). This precursor is subsequently amidated, adenylated, and oxidized to produce NAD+. The Preiss–Handler pathway utilizes dietary nicotinic acid (niacin) as a substrate, converting it directly into NaMN through nicotinic acid phosphoribosyltransferase. The salvage or recycling pathway recovers nicotinamide, a product of NAD+ consumption, through nicotinamide phosphoribosyltransferase (NAMPT) converting it into nicotinamide mononucleotide (NMN). NMN is then adenylated by NMN adenylyltransferases to yield NAD+. Each pathway can compensate for deficits in the others, ensuring robust NAD+ homeostasis.

NAD+ levels decline with age and under conditions of metabolic stress, contributing to mitochondrial dysfunction and impaired sirtuin activity. Pharmacological interventions, such as supplementation with nicotinamide riboside, nicotinamide mononucleotide, or activators of NAMPT, have been studied for their potential to restore NAD+ concentrations. Genetic manipulation in model organisms further illustrates the role of NADsyntetisaatioon in lifespan extension, resistance to oxidative damage, and modulation of immune responses. Understanding these pathways informs therapeutic strategies against age-related diseases, metabolic disorders, and neurodegeneration.