1-Methylnicotinamide

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1-Methylnicotinamide
1-Methylnicotinamide.svg
Names
Preferred IUPAC name
3-Carbamoyl-1-methylpyridin-1-ium
Other names
Trigonellamide; N1-Methylnicotinamide; NMN
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
PubChem CID
UNII
  • C[N+]1=CC=CC(=C1)C(=O)N
Properties
C7H9N2O+
Molar mass 137.161 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

1-Methylnicotinamide (trigonellamide) is a prototypic organic cation. [1] 1-Methylnicotinamide is the methylated amide of Nicotinamide (niacinamide, vitamin B3).

Contents

1-Methylnicotinamide is an endogenic substance that is produced in the liver when Nicotinamide is metabolized. It is a typical substance secreted in the kidney.

Occurrence

The highest natural concentration of 1-methylnicotinamide found so far is in the alga Undaria pinnatifida . [2] 1-Methylnicotinamide is also present in the Judas' ear fungus and in green tea. [2]

Extraction and production

1-Methylnicotinamide can be produced in the liver by nicotinamide N-methyltransferase. The reaction takes place during the metabolism of NAD (nicotinamide adenine dinucleotide).

NNMT (nicotinamide N-methyltransferase) is an enzyme that in humans is encoded by the NNMT gene. [3] NNMT catalyzes the methylation of nicotinamide and similar compounds using the methyl donor S-adenosyl methionine (SAM-e) to produce S-adenosyl-L-homocysteine (SAH) and 1-methylnicotinamide. [4] NNMT is highly expressed in the human liver. [4]

Use

For a long time, 1-methylnicotinamide was considered a biologically inactive metabolite of nicotinamide. However, various studies show antithrombotic, [5] anti-inflammatory, [6] gastroprotective [7] and vasoprotective [7] properties.

1-Methylnicotinamide is an endogenous activator of prostacyclin synthesis and can therefore regulate thrombolytic[ check spelling ] and inflammatory processes in the cardiovascular system. [8] It inhibits platelet-dependent thrombosis through a mechanism involving [9] cyclooxygenase-2 and prostacyclin and increases nitric oxide bioavailability in the endothelium. [7] [4]

Animal experiments with diabetic rats have shown that 1-methylnicotinamide has a positive effect on degenerative changes in the brain and cognitive performance can be thus longer maintained. [10]

Experiments with the nematode Caenorhabditis elegans showed that the addition of 1-methylnicotinamide can extend their lifespan. This may possibly be attributed to increased free radical binding and the resulting reduced oxidative stress. [11]

1-Methylnicotinamide is used in cosmetic products such as hair- and skincare products and as a dietary supplement. [12]

Related Research Articles

<span class="mw-page-title-main">Nicotinamide</span> Dietary supplement and medication

Niacinamide or nicotinamide is a form of vitamin B3 found in food and used as a dietary supplement and medication. As a supplement, it is used orally (swallowed by mouth) to prevent and treat pellagra (niacin deficiency). While nicotinic acid (niacin) may be used for this purpose, niacinamide has the benefit of not causing skin flushing. As a cream, it is used to treat acne, and has been observed in clinical studies to improve the appearance of aging skin by reducing hyperpigmentation and redness. It is a water-soluble vitamin. Niacinamide is the supplement name, while nicotinamide is the scientific name.

<span class="mw-page-title-main">Prostaglandin</span> Group of physiologically active lipid compounds

Prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids that have diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derived enzymatically from the fatty acid arachidonic acid. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring. They are a subclass of eicosanoids and of the prostanoid class of fatty acid derivatives.

<span class="mw-page-title-main">Cyclooxygenase</span> Class of enzymes

Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme that is responsible for biosynthesis of prostanoids, including thromboxane and prostaglandins such as prostacyclin, from arachidonic acid. A member of the animal-type heme peroxidase family, it is also known as prostaglandin G/H synthase. The specific reaction catalyzed is the conversion from arachidonic acid to prostaglandin H2 via a short-living prostaglandin G2 intermediate.

<span class="mw-page-title-main">Prostacyclin</span> Chemical compound

Prostacyclin (also called prostaglandin I2 or PGI2) is a prostaglandin member of the eicosanoid family of lipid molecules. It inhibits platelet activation and is also an effective vasodilator.

<span class="mw-page-title-main">Methyltransferase</span> Group of methylating enzymes

Methyltransferases are a large group of enzymes that all methylate their substrates but can be split into several subclasses based on their structural features. The most common class of methyltransferases is class I, all of which contain a Rossmann fold for binding S-Adenosyl methionine (SAM). Class II methyltransferases contain a SET domain, which are exemplified by SET domain histone methyltransferases, and class III methyltransferases, which are membrane associated. Methyltransferases can also be grouped as different types utilizing different substrates in methyl transfer reactions. These types include protein methyltransferases, DNA/RNA methyltransferases, natural product methyltransferases, and non-SAM dependent methyltransferases. SAM is the classical methyl donor for methyltransferases, however, examples of other methyl donors are seen in nature. The general mechanism for methyl transfer is a SN2-like nucleophilic attack where the methionine sulfur serves as the leaving group and the methyl group attached to it acts as the electrophile that transfers the methyl group to the enzyme substrate. SAM is converted to S-Adenosyl homocysteine (SAH) during this process. The breaking of the SAM-methyl bond and the formation of the substrate-methyl bond happen nearly simultaneously. These enzymatic reactions are found in many pathways and are implicated in genetic diseases, cancer, and metabolic diseases. Another type of methyl transfer is the radical S-Adenosyl methionine (SAM) which is the methylation of unactivated carbon atoms in primary metabolites, proteins, lipids, and RNA.

<span class="mw-page-title-main">Cyclooxygenase-2</span> Human enzyme involved in inflammation

Cyclooxygenase-2 (COX-2), also known as Prostaglandin-endoperoxide synthase 2 (HUGO PTGS2), is an enzyme that in humans is encoded by the PTGS2 gene. In humans it is one of three cyclooxygenases. It is involved in the conversion of arachidonic acid to prostaglandin H2, an important precursor of prostacyclin, which is expressed in inflammation.

Amine <i>N</i>-methyltransferase Class of enzymes

Amine N-methyltransferase, also called indolethylamine N-methyltransferase, and thioether S-methyltransferase, is an enzyme that is ubiquitously present in non-neural tissues and catalyzes the N-methylation of tryptamine and structurally related compounds. More recently, it was discovered that this enzyme can also catalyze the methylation of thioether and selenoether compounds, although the physiological significance of this biotransformation is not yet known.

In enzymology, a nicotinamide N-methyltransferase (NNMT) is an enzyme that catalyzes the chemical reaction

In enzymology, a tRNA (adenine-N1-)-methyltransferase (EC 2.1.1.36) is an enzyme that catalyzes the chemical reaction

In enzymology, a tRNA (guanine-N1-)-methyltransferase (EC 2.1.1.31) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">NNMT</span> Protein-coding gene in humans

Nicotinamide N-methyltransferase (NNMT) is an enzyme that in humans is encoded by the NNMT gene. NNMT catalyzes the methylation of nicotinamide and similar compounds using the methyl donor S-adenosyl methionine (SAM-e) to produce S-adenosyl-L-homocysteine (SAH) and 1-methylnicotinamide.

16S rRNA (adenine1408-N1)-methyltransferase (EC 2.1.1.180, kanamycin-apramycin resistance methylase, 16S rRNA:m1A1408 methyltransferase, KamB, NpmA, 16S rRNA m1A1408 methyltransferase) is an enzyme with systematic name S-adenosyl-L-methionine:16S rRNA (adenine1408-N1)-methyltransferase. This enzyme catalyses the following chemical reaction

23S rRNA (guanine745-N1)-methyltransferase (EC 2.1.1.187, Rlma(I), Rlma1, 23S rRNA m1G745 methyltransferase, YebH, RlmAI methyltransferase, ribosomal RNA(m1G)-methylase, rRNA(m1G)methylase, RrmA, 23S rRNA:m1G745 methyltransferase) is an enzyme with systematic name S-adenosyl-L-methionine:23S rRNA (guanine745-N1)-methyltransferase. This enzyme catalyses the following chemical reaction

23S rRNA (guanine748-N1)-methyltransferase (EC 2.1.1.188, Rlma(II), Rlma2, 23S rRNA m1G748 methyltransferase, RlmaII, Rlma II, tylosin-resistance methyltransferase RlmA(II), TlrB, rRNA large subunit methyltransferase II) is an enzyme with systematic name S-adenosyl-L-methionine:23S rRNA (guanine748-N1)-methyltransferase. This enzyme catalyses the following chemical reaction

23S rRNA (guanine2535-N1)-methyltransferase (EC 2.1.1.209, AviRa) is an enzyme with systematic name S-adenosyl-L-methionine:23S rRNA (guanine2535-N1)-methyltransferase. This enzyme catalyses the following chemical reaction

TRNA (adenine57-N1/adenine58-N1)-methyltransferase (EC 2.1.1.219, TrmI, PabTrmI, AqTrmI, MtTrmI) is an enzyme with systematic name S-adenosyl-L-methionine:tRNA (adenine57/adenine58-N1)-methyltransferase. This enzyme catalyses the following chemical reaction:

TRNA (adenine58-N1)-methyltransferase (EC 2.1.1.220, tRNA m1A58 methyltransferase, tRNA (m1A58) methyltransferase, TrmI, tRNA (m1A58) Mtase, Rv2118cp, Gcd10p-Gcd14p, Trm61p-Trm6p) is an enzyme with systematic name S-adenosyl-L-methionine:tRNA (adenine58-N1)-methyltransferase. This enzyme catalyses the following chemical reaction

TRNA (pseudouridine54-N1)-methyltransferase (EC 2.1.1.257, TrmY, m1Psi methyltransferase) is an enzyme with systematic name S-adenosyl-L-methionine:tRNA (pseudouridine54-N1)-methyltransferase. This enzyme catalyses the following chemical reaction

RRNA small subunit pseudouridine methyltransferase Nep1 (EC 2.1.1.260, Nep1, nucleolar essential protein 1) is an enzyme with systematic name S-adenosyl-L-methionine:18S rRNA (pseudouridine1191-N1)-methyltransferase. This enzyme catalyses the following chemical reaction

<span class="mw-page-title-main">12-Hydroxyheptadecatrienoic acid</span> Chemical compound

12-Hydroxyheptadecatrienoic acid (also termed 12-HHT, 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid, or 12(S)-HHTrE) is a 17 carbon metabolite of the 20 carbon polyunsaturated fatty acid, arachidonic acid. It was discovered and structurally defined in 1973 by P. Wlodawer, Bengt I. Samuelsson, and M. Hamberg, as a product of arachidonic acid metabolism made by microsomes (i.e. endoplasmic reticulum) isolated from sheep seminal vesicle glands and by intact human platelets. 12-HHT is less ambiguously termed 12-(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid to indicate the S stereoisomerism of its 12-hydroxyl residue and the Z, E, and E cis-trans isomerism of its three double bonds. The metabolite was for many years thought to be merely a biologically inactive byproduct of prostaglandin synthesis. More recent studies, however, have attached potentially important activity to it.

References

  1. ↑ Sokol, P. P.; Holohan, P. D.; Ross, C. R. (1986). "Essential disulfide and sulfhydryl groups for organic cation transport in renal brush-border membranes". Journal of Biological Chemistry . 261 (7): 3282–3287. doi: 10.1016/S0021-9258(17)35779-4 . PMID   2936734 . Retrieved 5 March 2021.
  2. 1 2 Taguchi, H.; Sakaguchi, M.; Shimabayashi, Y. (1986). 各種食品中のキノリン酸,トリゴネリンおよびN1-メチルニコチンアミドの含量ならびに加熱によるそれらのニコチン酸,ニコチンアミドへの変換[Contents of quinolinic acid, trigonelline and N1-methylnicotinamide in various foods and thermal conversion of these compounds into nicotinic acid and nicotinamide]. ビタミンビタミン[Vitamins] (in Japanese). 60 (11): 537–546. doi:10.20632/vso.60.11_537.
  3. ↑ Aksoy S, Brandriff BF, Ward A, Little PF, Weinshilboum RM (Mar 1996). "Human nicotinamide N-methyltransferase gene: molecular cloning, structural characterization and chromosomal localization". Genomics. 29 (3): 555–561. doi:10.1006/geno.1995.9966. PMID   8575745.
  4. 1 2 3 Pissios P (2017). "Nicotinamide N-Methyltransferase: More Than a Vitamin B3 Clearance Enzyme". Trends in Endocrinology and Metabolism . 28 (5): 340–353. doi:10.1016/j.tem.2017.02.004. PMC   5446048 . PMID   28291578.
  5. ↑ Gębicki, J.; Sysa-Jędrzejowska, A.; Adamus, J.; Woźniacka, A.; Rybak, M.; Zielonka, J. (2003). "1-Methylnicotinamide: A potent anti-inflammatory agent of vitamin origin" (PDF). Polish Journal of Pharmacology. 55 (1): 109–112. PMID   12856834.
  6. ↑ Bryniarski, K.; Biedron, R.; Jakubowski, A.; Chlopicki, S.; Marcinkiewicz, J. (2008). "Anti-inflammatory effect of 1-methylnicotinamide in contact hypersensitivity to oxazolone in mice; involvement of prostacyclin". European Journal of Pharmacology . 578 (2–3): 332–338. doi:10.1016/j.ejphar.2007.09.011. PMID   17935712.
  7. 1 2 3 Domagala, T. B.; Szeffler, A.; Dobrucki, L. W.; Dropinski, J.; Polanski, S.; Leszczynska-Wiloch, M.; Kotula-Horowitz, K.; Wojciechowski, J.; Wojnowski, L.; Szczeklik, A.; Kalinowski, L. (2012). "Nitric oxide production and endothelium-dependent vasorelaxation ameliorated by N1-methylnicotinamide in human blood vessels". Hypertension . 59 (4): 825–832. doi: 10.1161/HYPERTENSIONAHA.111.183210 . PMID   22353616. S2CID   302943.
  8. ↑ Bartuś, M.; Łomnicka, M.; Kostogrys, R. B.; Kaźmierczak, P.; Watała, C.; Słominska, E. M.; Smoleński, R. T.; Pisulewski, P. M.; Adamus, J.; Gębicki, J.; Chlopicki, S. (2008). "1-Methylnicotinamide (MNA) prevents endothelial dysfunction in hypertriglyceridemic and diabetic rats" (PDF). Pharmacological Reports. 60 (1): 127–138. PMID   18276994.
  9. ↑ Chlopicki, S.; Swies, J.; Mogielnicki, A.; Buczko, W.; Bartus, M.; Lomnicka, M.; Adamus, J.; Gebicki, J. (2007). "1-Methylnicotinamide (MNA), a primary metabolite of nicotinamide, exerts anti-thrombotic activity mediated by a cyclooxygenase-2/prostacyclin pathway". British Journal of Pharmacology . 152 (2): 230–239. doi:10.1038/sj.bjp.0707383. PMC   1978255 . PMID   17641676.
  10. ↑ Kuchmerovska, T.; Shymanskyy, I.; Chlopicki, S.; Klimenko, A. (2010). "1-Methylnicotinamide (MNA) in prevention of diabetes-associated brain disorders". Neurochemistry International . 56 (2): 221–228. doi:10.1016/j.neuint.2009.10.004. PMID   19837120. S2CID   21785102.
  11. ↑ Schmeisser, K.; Mansfeld, J.; Kuhlow, D.; Weimer, S.; et al. (2013). "Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide". Nature Chemical Biology . 9 (11): 693–700. doi:10.1038/nchembio.1352. PMC   4076143 . PMID   24077178.
  12. ↑ "Menavitin Produkte, die das Molekül 1-MNA beinhalten: das Novel Food mit natürlicher Intelligenz". Startup Valley (in German). 21 November 2019. Retrieved 29 January 2020.
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