What is Nicotinamide Mononucleotide?
Nicotinamide mononucleotide is considered as one of the intermediate in the biosynthesis of NAD+ and it also acts as a bioactive nucleotide, which is formed during the reaction between the nucleoside containing ribosome and the phosphate group.
Nicotinamide Mononucleotide plays an important role in converting the NAM into NMN directly with the help of a nicotinamide phosphoribosyl transferase.
The molecular weight of the NMN is about 334.221 gram per mol. There are about two anomeric forms of the NMN which are named as alpha and the beta, in this beta is in the active form.
Nicotinamide mononucleotide can be found in various types of natural food substances like vegetables, meat and fruits. Recent clinical studies have determined that on administration of the NMN is generally compensated for the deficiency of NAD+ and the NMN supplements which has the ability to affect the various pharmacological activities in various diseases.
Nicotinamide Mononucleotide Biosynthesis
Nicotinamide mononucleotide is one of the nucleotides which is derived from the ribosome and the nicotinamide. Nicotinamide is derived from the niacin. Human contains enzymes which utilizes Nicotinamide mononucleotides to generate the nicotinamide adenine dinucleotide.
Generally, in mice Nicotinamide mononucleotide is used proposed into the cells of them through the small intestine within 10 minutes of converting them into NAD+ with the help of a Sic 12a8 transporter.
As NADH acts a cofactor in the processes that takes place in the mitochondria, for skirtinis and the PARP, nicotinamide mononucleotide can also be used for the purpose of studying the animal models, which acts as a potential neuroprotective and the antiaging agent.
Usually, the Dietary suppling industries use these aggressively marketed nicotinamide mononucleotide proceeds for utilizing the advantages of this.
The molecular structures of the Nicotinamide mononucleotide and the Nicotinamide riboside looks almost similar, except the phosphate groups which makes the nicotinamide mononucleotide as a large molecule.
Nicotinamide Mononucleotide Benefits
It greatly helps in suppressing the age-related problems like weight again, enhancing the energy metabolisms and in improving the physical activities.
NMN also greatly helps in improving the sensitivity of the insulin.
It also helps in increasing the functioning of the eye and also in improving the mitochondrial metabolisms.
NMN also plays a vital role in preventing the age-linked changes which affects the expression of the genes.
Pharmacological Benefits of Nicotinamide Mononucleotide
NMN plays an important role in modern therapeutic agents which demonstrates the various beneficial biochemical activities in many preclinical diseases including those of myocardial and the cerebral ischemia, neurodegenerative disorders like the diabetes and the Alzheimer’s disease. Recently it has also been identified that NMN play a major role in treating the antiaging effects.
NAD+ Biosynthesis Pathways
There are about three different pathways of NAD+ biosynthesis which are described in cells of the mammals. It includes
i. Preiss-Handler Pathway – where the NAD is synthesized from nictonic acid.
ii. De novo Synthesis – which starts from the tryptophan
iii. Salvage Pathway – is one of the most predominant in the cells of the mammals.
i. Preiss – Handler Pathway
This pathway starts with conversion of the Nictotinamide into nicotinic acid mononucleotide (NAMN) with the help of an enzyme nicotinic acid phosphoribosyl transferase. Further NAMN is used for the biosynthesis of nicotinamide. At last, the NAD+ synthetase converts NAAD+ into NAD+ with the help of the ammonia and the ATP action as the extra ingredients.
ii. De novo Synthesis from Tryptophan
De novo synthesis pathway usually occurs in eight step process which is being initiated by the indoleamine 2, 3- dioxygenase or the tryptophan 2, 3-dioxygenase which helps in converting the tryptophan into the N-formylkynureine.
Formylkynureinine is further transferred into kynurenine, to which the hydroxyl is added through the kynurenine -3-hydroxylase. The resultant product 3-hydroxy kynurenine which will be converted into 3-hydroxyanthranilate which will be further followed by the 2-amino-3-carboxymuconate semialdehyde through the enzyme kynureninase and the 3-hydroxyxyanthramilate-3, 4-dioxygenase. The formed 2-amino-3 carboxymuconate further cyclizes to form a quinolic acid which participates in the process of NAMN biosynthesis in the quinolinate phosphoribosyl transferase.
iii. Salvage Pathway
Salvage pathway most predominantly occurs in the mammalian cells. During this pathway, the intermediate degradative products of the NAD+ such as the nicotinamide and the nicotinic acids are reused to form a new product named NAD+.
This pathway is most commonly involved in the conversion of the nicotinic into the nicotinic acid mononucleotide with the help of the enzyme nicotinate phosphoribosyl transferase which is further followed by adenylation of the nicotinic acid adenine dinucleotide during the presence of the nicotinamide mononucleotide adenylyl transferase-1, 3.
In few cases, nicotinic acid will be directly converted into nicotinic acid phosphoribosyl transferase which is further converted into NAD+ with the help of the NAD+ synthetase enzyme. During this pathway, NAD+ is degraded to form a nicotinamide by the NAD+ consuming enzymes.
Which is further followed by converting the NMN by the catalytic activity of the nicotinamide phosphoribosyl transferase. This enzyme helps in transferring the phosphoribosyl residue from the phosphoribosylpyrophospahte.
Nicotinamide Mononucleotide Citations
- Multi-targeted Effect of Nicotinamide Mononucleotide on Brain Bioenergetic Metabolism. Neurochem Res . 2019 Oct;44(10):2280-2287.
- Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ Metabolism. Front Cell Dev Biol . 2020 Apr 28;8:246.
- Nicotinamide Mononucleotide: Exploration of Diverse Therapeutic Applications of a Potential Molecule. Biomolecules . 2019 Jan 21;9(1):34.