Longevity Science
According to current research, NMN is an effective and stable method to increase NAD+ levels while ensuring optimal bioavailability and maximum longevity benefits.
Introduction to the Biochemistry of NMN: A Key Player in Cellular Energy Metabolism
For countless generations, we have striven to unravel the mysteries of biochemical processes. While our ancestors focused on phenomena they could see with their own eyes, today our gaze is increasingly directed towards the molecular level. We are constantly discovering new molecules on the horizon of science, which we try to fit into the existing schemes of biochemistry and biology. One such rising star in this universe of molecules is nicotinamide mononucleotide (NMN) , a molecule that has become increasingly the focus of research in recent years. Come with us on an accessible journey of discovery into biochemistry as we take a closer look at NMN, a leading player in the realm of NAD.
The world of organisms is breathtakingly complex, with countless processes taking place in fractions of a second. All of these processes are based on one elementary building block: energy. Organisms obtain energy from food, which is broken down into its basic components and ultimately assimilated. Similar to the conversion of solar heat into electricity, molecules must also be converted into a usable form of energy at the cellular level. This essential conversion takes place in the mitochondria, the energy centers of the cell. There, the enzyme ATP synthase produces adenosine triphosphate (ATP), a universal and immediately available energy carrier in cells and thus in the entire organism. ATP synthase is supported by NAD+, an essential cofactor. NMN serves as a precursor to NAD+ and thus plays a key role in this energetic cycle.
Before we delve deeper into the subject, let us first take a closer look at some of these technical terms.
What is an enzyme?
What is an enzyme?
Similar to hormones and antibodies, enzymes are made of proteins, the basic building blocks of life.
In our bodies, countless enzymes act as biocatalysts every second to control a variety of biological processes. This function is similar to that of catalysts in vehicles: they are substances that can influence the rate of chemical reactions without themselves being consumed. Simply put, enzymes allow biological reactions to take place under less demanding conditions.
The breakdown of substances by enzymes is called catabolism, whereby complex molecules are converted into simpler ones. On the other hand, enzymes can also be involved in the construction of substances, a process known as anabolism. A prominent example of this is the enzyme ATP synthase (adenosine triphosphate synthase), which typically ends in -ase and, together with NAD+, plays a crucial role in the energy supply in living organisms.
What is NAD+ and what is a coenzyme?
What is NAD+ and what is a coenzyme?
NAD+ stands for nicotinamide adenine dinucleotide, with the plus sign symbolizing a positive electrical charge. It is a coenzyme that is found in almost every cell in the body. Coenzymes are small organic molecules that are essential for activating enzymes and thus for starting chemical reactions. An appropriate NAD+ level is of great importance for many cellular processes. However, the amount of NAD+ decreases over time, which is rather detrimental to the organism.
NAD+ is formed in the body by synthesis from certain precursors, a process that occurs via three different pathways. A simplified representation of the three synthesis pathways includes the "de novo" pathway, which begins with tryptophan as the starting material, the "Preiss-Handler" pathway, which uses niacin as a base, and the "salvage pathway," which allows NAD to be recycled in the body. "Salvage" means something like "to salvage" or "to save." In this context , nicotinamide mononucleotide (NMN) plays a key role.
NMN acts as the central precursor molecule for NAD in the salvage pathway. This means that NMN is an essential intermediate for the synthesis of NAD from other precursors such as nicotinamide riboside (NR) or nicotinamide (Nam). This makes NMN essential for maintaining and restoring NAD levels in the body. Let's take a closer look at this crucial molecule.
What is NMN?
NMN, short for nicotinamide mononucleotide , is a derivative of vitamin B3 and plays a central role in the biosynthesis of NAD+ in all living organisms.
NAD+ (nicotinamide adenine dinucleotide) is a coenzyme involved in a variety of cellular processes, particularly in energy metabolism and DNA repair. Since NAD+ declines with age, NMN is considered a potential agent to increase NAD+ levels and is therefore an important area of research in anti-aging and longevity.
How NMN Increases NAD+ Levels
Nicotinamide mononucleotide (NMN) is an essential intermediate in the salvage pathway , one of the main pathways for the synthesis of nicotinamide adenine dinucleotide (NAD+). NAD+ is an essential coenzyme involved in virtually all cellular processes, including energy metabolism, DNA repair, and circadian rhythm regulation. However, NAD+ concentrations decline with age, which may lead to a loss of cellular function and an increased risk of age-related diseases. NMN supplementation is being investigated as a promising method to increase NAD+ levels in the body.
Biochemical pathways of NAD+ biosynthesis
There are three main pathways by which NAD+ is synthesized in the body:
- De novo synthesis from the amino acid tryptophan.
- Preiss-Handler pathway , which uses the precursor niacin (vitamin B3).
- Salvage Pathway , which recycles nicotinamide (a form of vitamin B3).
NMN plays a central role in the salvage pathway, which produces about 85-90% of all NAD+ in the human body. This recycling pathway is so named because it reclaims the nicotinamide released when NAD+ is converted to NADH and converts it back into NAD+.
Conversion of NMN to NAD+
The key mechanism by which NMN increases NAD+ levels is its conversion to NAD+ by the enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT). This process can be summarized in the following steps:
- Cellular uptake of NMN : NMN can be taken up into cells through various transport mechanisms. A recently discovered protein, Slc12a8 , has been identified as a specific NMN transporter, particularly present in intestinal cells. This transporter plays a crucial role in the rapid uptake of NMN, especially in older organisms whose NAD+ levels are already severely reduced.
- Conversion to NAD+ : Once NMN enters the cell, it is converted to NAD+ by the enzyme NMNAT. NMNAT exists in several isoforms (NMNAT1, NMNAT2, and NMNAT3), each active in different cellular compartments (such as the nucleus, cytosol, and mitochondria). These isoforms are crucial for ensuring that NAD+ synthesis can occur in different cellular environments.
- Role of NAD+ in cellular processes : After conversion to NAD+, the coenzyme performs a variety of functions. One of the most important is providing electrons for redox reactions in the mitochondrial respiratory chain. These processes are crucial for ATP production , the primary energy source of cells.
regeneration of the NAD+ pool
Another mechanism by which NMN contributes to increasing NAD+ levels is the activation of sirtuins . Sirtuins are NAD+-dependent enzymes that regulate various cellular processes, including gene expression, DNA repair, and metabolism. When NAD+ is used as a cofactor for sirtuins, it is converted to nicotinamide (NAM). NMN plays a crucial role in recycling NAM to NAD+ via the salvage pathway. This recycling process allows the NAD+ pool to be maintained.
Aging processes and the NAD+ decline
With age, the body's capacity to synthesize NAD+ decreases, leading to a decline in cellular energy production and the ability to repair DNA. This NAD+ decline is caused, among other things, by the increased activity of CD38 , an NAD+-degrading enzyme. Studies show that NMN supplementation can increase NAD+ levels and at least partially reverse age-related functional losses in cells and tissues.
Effects of NMN Supplementation
Several preclinical studies have shown that NMN supplementation effectively increases NAD+ levels in various organisms, including mice and humans:
- Improved mitochondrial function : Studies in mice have shown that NMN improves mitochondrial functions by increasing ATP production and reducing oxidative stress.
- Delaying age-related diseases : NMN has shown positive effects on age-related diseases such as type 2 diabetes, neurodegenerative diseases and cardiovascular problems in animal studies.
- Human Studies : Initial clinical studies in humans have shown that NMN is safe and can significantly increase NAD+ levels in tissues, leading to improved physical endurance and potentially slowing the aging process.
Manufacturing & Quality
The chemical production of NMN is a particularly complex and costly process because it mimics the natural conversion of nicotinamide riboside (NR) to NMN.
Because of these production challenges and the fact that NMN was until recently used exclusively in research, the molecule is relatively expensive. It is therefore not surprising that NMN is one of the most counterfeited substances in the world.
A recent study conducted in the US that examined 22 different NMN suppliers revealed disappointing results. More than half of the products tested did not contain authentic NMN or were of inferior quality.
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