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| 1-methylnicotinamide |
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| CHEBI:16797 |
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| A pyridinium ion comprising nicotinamide having a methyl group at the 1-position. It is a metabolite of nicotinamide which was initially considered to be biologically inactive but has emerged as an anti-thrombotic and anti-inflammatory agent. |
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This entity has been manually annotated by the ChEBI Team.
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CHEBI:646, CHEBI:18635, CHEBI:11267
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| eMolecules:3800986, ZINC000000155368 |
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Molfile
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more structures >>
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call loadScript javascripts\jsmol\core\package.js call loadScript javascripts\jsmol\core\core.z.js -- required by ClazzNode call loadScript javascripts\jsmol\J\awtjs2d\WebOutputChannel.js Jmol JavaScript applet jmolApplet0_object__698153618751506__ initializing getValue debug = null getValue logLevel = null getValue allowjavascript = null AppletRegistry.checkIn(jmolApplet0_object__698153618751506__) call loadScript javascripts\jsmol\core\corestate.z.js viewerOptions: { "name":"jmolApplet0_object","applet":true,"documentBase":"https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:18635","platform":"J.awtjs2d.Platform","fullName":"jmolApplet0_object__698153618751506__","display":"jmolApplet0_canvas2d","signedApplet":"true","appletReadyCallback":"Jmol._readyCallback","statusListener":"[J.appletjs.Jmol.MyStatusListener object]","codeBase":"https://www.ebi.ac.uk/chebi/javascripts/jsmol/","syncId":"698153618751506","bgcolor":"#000" } (C) 2012 Jmol Development Jmol Version: 13.2.7 $Date: 2013-10-01 11:35:15 -0500 (Tue, 01 Oct 2013) $ java.vendor: j2s java.version: 0.0 os.name: j2s Access: ALL memory: 0.0/0.0 processors available: 1 useCommandThread: false appletId:jmolApplet0_object (signed) starting HoverWatcher_1 getValue emulate = null defaults = "Jmol" getValue boxbgcolor = null getValue bgcolor = #000 backgroundColor = "#000" getValue ANIMFRAMECallback = null getValue APPLETREADYCallback = Jmol._readyCallback APPLETREADYCallback = "Jmol._readyCallback" getValue ATOMMOVEDCallback = null getValue CLICKCallback = null getValue ECHOCallback = null getValue ERRORCallback = null getValue EVALCallback = null getValue HOVERCallback = null getValue LOADSTRUCTCallback = null getValue MEASURECallback = null getValue MESSAGECallback = null getValue MINIMIZATIONCallback = null getValue PICKCallback = null getValue RESIZECallback = null getValue SCRIPTCallback = null getValue SYNCCallback = null getValue STRUCTUREMODIFIEDCallback = null getValue doTranslate = null language=en_US getValue popupMenu = null getValue script = null Jmol applet jmolApplet0_object__698153618751506__ ready call loadScript javascripts\jsmol\core\corescript.z.js call loadScript javascripts\jsmol\J\script\FileLoadThread.js starting QueueThread0_2 script 1 started starting HoverWatcher_3 starting HoverWatcher_4 The Resolver thinks Mol 8GC - Ideal conformer Mrv1927 07162110543D starting HoverWatcher_5 Time for openFile(8GC - Ideal conformer Mrv1927 07162110543D 19 19 0 0 0 0 999 V2000 -1.9500 0.3290 -0.0010 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5400 -0.1170 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2250 -1.4800 0.0010 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1110 -1.8450 0.0010 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0810 -0.8590 0.0010 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8190 1.4260 0.0010 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4990 0.8160 -0.0060 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7540 0.4190 0.0010 N 0 3 0 0 0 4 0 0 0 0 0 0 -2.9440 -0.5810 -0.0010 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.2120 1.5160 0.0040 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0030 -2.2290 0.0010 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3920 -2.8880 0.0020 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1240 -1.1410 0.0010 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0830 1.6750 -1.0270 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4710 2.3220 0.5150 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6940 1.0290 0.5150 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2710 1.8710 -0.0100 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8690 -0.2890 0.0020 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7350 -1.5280 -0.0050 H 0 0 0 0 0 0 0 0 0 0 0 0 5 4 2 0 0 0 0 5 8 1 0 0 0 0 4 3 1 0 0 0 0 6 8 1 0 0 0 0 8 7 2 0 0 0 0 3 2 2 0 0 0 0 7 2 1 0 0 0 0 2 1 1 0 0 0 0 1 9 1 0 0 0 0 1 10 2 0 0 0 0 3 11 1 0 0 0 0 4 12 1 0 0 0 0 5 13 1 0 0 0 0 6 14 1 0 0 0 0 6 15 1 0 0 0 0 6 16 1 0 0 0 0 7 17 1 0 0 0 0 9 18 1 0 0 0 0 9 19 1 0 0 0 0 M CHG 1 8 1 M END): 15 ms reading 19 atoms ModelSet: haveSymmetry:false haveUnitcells:false haveFractionalCoord:false 1 model in this collection. Use getProperty "modelInfo" or getProperty "auxiliaryInfo" to inspect them. Default Van der Waals type for model set to Babel 19 atoms created ModelSet: not autobonding; use forceAutobond=true to force automatic bond creation Script completed Jmol script terminated
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| 1-Methylnicotinamide (1-MNA, trigonellamide) is a prototypic organic cation. 1-Methylnicotinamide is the methylated amide of Nicotinamide (niacinamide, vitamin B3).
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. It participates in the nicotinamide salvage pathway within the NAD+ (nicotinamide adenine dinucleotide) metabolic pathway, thereby contributing to optimizing NAD+ levels. |
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Read full article at Wikipedia
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| InChI=1S/C7H8N2O/c1-9-4-2-3-6(5-9)7(8)10/h2-5H,1H3,(H-,8,10)/p+1 |
| LDHMAVIPBRSVRG-UHFFFAOYSA-O |
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Mus musculus
(NCBI:txid10090)
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Source: BioModels - MODEL1507180067
See:
PubMed
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Saccharomyces cerevisiae
(NCBI:txid4932)
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Source: yeast.sf.net
See:
PubMed
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Undaria pinnatifida
(NCBI:txid74381)
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See:
DOI
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Homo sapiens
(NCBI:txid9606)
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See:
DOI
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Homo sapiens
(NCBI:txid9606)
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Found in
blood
(UBERON:0000178).
See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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Found in
urine
(BTO:0001419).
See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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From MetaboLights
See:
MetaboLights Study
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Homo sapiens
(NCBI:txid9606)
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From MetaboLights
See:
MetaboLights Study
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Homo sapiens
(NCBI:txid9606)
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From MetaboLights
See:
MetaboLights Study
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Homo sapiens
(NCBI:txid9606)
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From MetaboLights
See:
MetaboLights Study
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Saccharomyces cerevisiae metabolite
Any fungal metabolite produced during a metabolic reaction in Baker's yeast (Saccharomyces cerevisiae ).
mouse metabolite
Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
human urinary metabolite
Any metabolite (endogenous or exogenous) found in human urine samples.
algal metabolite
Any eukaryotic metabolite produced during a metabolic reaction in algae including unicellular organisms like chlorella and diatoms to multicellular organisms like giant kelps and brown algae.
plant metabolite
Any eukaryotic metabolite produced during a metabolic reaction in plants, the kingdom that include flowering plants, conifers and other gymnosperms.
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anti-inflammatory agent
Any compound that has anti-inflammatory effects.
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View more via ChEBI Ontology
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3-carbamoyl-1-methylpyridinium
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1-methyl nicotinamide
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ChemIDplus
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1-Methylnicotinamide
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KEGG COMPOUND
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1-methylnicotinamide
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UniProt
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1-methylnicotinamide cation
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ChEBI
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3-(aminocarbonyl)-1-methylpyridinium
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ChemIDplus
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3-carbamoyl-1-methylpyridin-1-ium
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HMDB
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N(1)-Methylnicotinamide
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ChemIDplus
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N-1-methylnicotinamide
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HMDB
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N1-methylnicotinamide
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HMDB
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Trigonellinamide
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ChemIDplus
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3106-60-3
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CAS Registry Number
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ChemIDplus
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3540351
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Reaxys Registry Number
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Reaxys
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Nguyen VL, Saldanha R, Fitzpatrick M (2021)
Dual Analysis of N-methyl-2-pyridone-5-carboxamide and N-1-methylnicotinamide in Urine by HPLC with UV Detection.
Journal of chromatographic science 59, 770-775 [PubMed:33442746]
[show Abstract]
N-methyl-2-pyridone-5-carboxamide (2PYr) and N-1-methylnicotinamide (NMN) are metabolites of the water soluble Vitamin B3 (Nicotinamide). Limited methodologies exist for their dual chromatographic analysis in urine samples. In this study, we developed a method for analysis of both 2PYr and NMN by ultraviolet detection. Urine samples were treated to a salting-out assisted liquid/liquid extraction for the extraction of 2PYr and cation exchange for NMN. Both analytes were separated on a Biphenyl 100 × 2.1 mm, 2.6-μm column. The new assay's performance (specifically 2PYr) was compared against the existing testing protocol (based on a previously published method). Linearity for both analytes was above 0.99 (r2) up to a concentration range of: 1500 μmol/L (2PYr) and 150 μmol/L (NMN). Intra-assay and inter-assay precision of the method was below 8% (coefficient of variation) except at the lower limit of quantification where it was below 20%. Recovery of 2PYr was above 80% and NMN above 90%. A significant positive bias was observed with 2PYr against the existing method. This new method allows for both 2PYr and NMN to be chromatographed and overcomes sample preparation issues in urine 2PYr analysis. | Kilgour MK, MacPherson S, Zacharias LG, Ellis AE, Sheldon RD, Liu EY, Keyes S, Pauly B, Carleton G, Allard B, Smazynski J, Williams KS, Watson PH, Stagg J, Nelson BH, DeBerardinis RJ, Jones RG, Hamilton PT, Lum JJ (2021)
1-Methylnicotinamide is an immune regulatory metabolite in human ovarian cancer.
Science advances 7, eabe1174 [PubMed:33523930]
[show Abstract]
Immune regulatory metabolites are key features of the tumor microenvironment (TME), yet with a few exceptions, their identities remain largely unknown. Here, we profiled tumor and T cells from tumor and ascites of patients with high-grade serous carcinoma (HGSC) to uncover the metabolomes of these distinct TME compartments. Cells within the ascites and tumor had pervasive metabolite differences, with a notable enrichment in 1-methylnicotinamide (MNA) in T cells infiltrating the tumor compared with ascites. Despite the elevated levels of MNA in T cells, the expression of nicotinamide N-methyltransferase, the enzyme that catalyzes the transfer of a methyl group from S-adenosylmethionine to nicotinamide, was restricted to fibroblasts and tumor cells. Functionally, MNA induces T cells to secrete the tumor-promoting cytokine tumor necrosis factor alpha. Thus, TME-derived MNA contributes to the immune modulation of T cells and represents a potential immunotherapy target to treat human cancer. | Agudiez M, Martinez PJ, Martin-Lorenzo M, Heredero A, Santiago-Hernandez A, Molero D, Garcia-Segura JM, Aldamiz-Echevarria G, Alvarez-Llamas G (2020)
Analysis of urinary exosomal metabolites identifies cardiovascular risk signatures with added value to urine analysis.
BMC biology 18, 192 [PubMed:33317539]
[show Abstract]
BackgroundSubclinical atherosclerosis may result in fatal cardiovascular (CV) events, but the underlying mechanisms and molecular players leading to disease are not entirely understood. Thus, novel approaches capable of identifying the factors involved in pathological progression and providing a better understanding of the subjacent mechanisms are needed. Extracellular vesicles (EVs) have been shown to have numerous biological functions, and their metabolome has recently generated interest as a source of novel biomarkers. The metabolic content of the exosomes has been so far unexplored in cardiovascular disease (CVD), and here, we developed an analytical strategy aimed at probing urinary exosomal metabolite content and its association to CV risk.ResultsDirect analysis of the exosomes without metabolite extraction was evaluated by high-resolution magic angle spinning (1H HR-MAS). Other two methodologies for the analysis of exosomal metabolites by 1H NMR were set up, based on methanol or organic solvents sequential extraction. The three methods were compared in terms of the number of detected signals and signal to noise ratio (S/N). The methanol method was applied to identify altered metabolites in the urinary exosomes of subjects with programmed coronary artery by-pass grafting (CABG) versus a control group. Target mass spectrometry (MS) was also performed for differential analysis. The clinical performance of exosomal metabolites of interest in CVD was investigated, and the added value of the exosomes compared to urine analysis was evaluated. Based on S/N ratio, simplicity, reproducibility, and quality of the spectrum, the methanol method was chosen for the study in CVD. A cardiometabolic signature composed by 4-aminohippuric acid, N-1-methylnicotinamide, and citric acid was identified in urinary exosomes. Directly in urine, 4-aminohippuric acid and citric acid do not show variation between groups and changes in N-1-methylnicotinamide are less pronounced, proving the added value of exosomes.ConclusionsWe set up a novel methodology to analyze metabolic alterations in urinary exosomes and identified a cardiometabolic signature in these microvesicles. This study constitutes the first evidence of a role for the exosomal metabolism in CVD and demonstrates the possibility to evaluate the urinary exosomal metabolic content by NMR and MS. | Swaminathan S, Birudukota S, Thakur MK, Parveen R, Kandan S, Juluri S, Shaik S, Anand NN, Burri RR, Kristam R, Hallur MS, Rajagopal S, Schreuder H, Langer T, Rudolph C, Ruf S, Dhakshinamoorthy S, Gosu R, Kannt A (2017)
Crystal structures of monkey and mouse nicotinamide N-methyltransferase (NNMT) bound with end product, 1-methyl nicotinamide.
Biochemical and biophysical research communications 491, 416-422 [PubMed:28720493]
[show Abstract]
Nicotinamide N-methyltransferase (NNMT) is a S-adenosyl-l-methionine (SAM)-dependent enzyme that catalyzes N-methylation of nicotinamide (NA) and other pyridines to form N-methyl pyridinium ions. Here we report the first ternary complex X-ray crystal structures of monkey NNMT and mouse NNMT in bound form with the primary endogenous product, 1-methyl nicotinamide (MNA) and demethylated cofactor, S-adenosyl-homocysteine (SAH) determined at 2.30 Å and 1.88 Å respectively. The structural fold of these enzymes is identical to human NNMT. It is known that the primary endogenous product catalyzed by NNMT, MNA is a specific inhibitor of NNMT. Our data clearly indicates that the MNA binds to the active site and it would be trapped in the active site due to the formation of the bridge between the pole (long helix, α3) and long C-terminal loop. This might explain the mechanism of MNA acting as a feedback inhibitor of NNMT. | Bar A, Olkowicz M, Tyrankiewicz U, Kus E, Jasinski K, Smolenski RT, Skorka T, Chlopicki S (2017)
Functional and Biochemical Endothelial Profiling In Vivo in a Murine Model of Endothelial Dysfunction; Comparison of Effects of 1-Methylnicotinamide and Angiotensin-converting Enzyme Inhibitor.
Frontiers in pharmacology 8, 183 [PubMed:28443021]
[show Abstract]
Although it is known that 1-methylnicotinamide (MNA) displays vasoprotective activity in mice, as yet the effect of MNA on endothelial function has not been demonstrated in vivo. Here, using magnetic resonance imaging (MRI) we profile the effects of MNA on endothelial phenotype in mice with atherosclerosis (ApoE/LDLR-/-) in vivo, in comparison to angiotensin (Ang) -converting enzyme (ACE) inhibitor (perindopril), with known vasoprotective activity. On a biochemical level, we analyzed whether MNA- or perindopril-induced improvement in endothelial function results in changes in ACE/Ang II-ACE2/Ang-(1-7) balance, and L-arginine/asymmetric dimethylarginine (ADMA) ratio. Endothelial function and permeability were evaluated in the brachiocephalic artery (BCA) in 4-month-old ApoE/LDLR-/- mice that were non-treated or treated for 1 month or 2 months with either MNA (100 mg/kg/day) or perindopril (10 mg/kg/day). The 3D IntraGate®FLASH sequence was used for evaluation of BCA volume changes following acetylcholine (Ach) administration, and for relaxation time (T1) mapping around BCA to assess endothelial permeability using an intravascular contrast agent. Activity of ACE/Ang II and ACE2/Ang-(1-7) pathways as well as metabolites of L-arginine/ADMA pathway were measured using liquid chromatography/mass spectrometry-based methods. In non-treated 6-month-old ApoE/LDLR-/- mice, Ach induced a vasoconstriction in BCA that amounted to -7.2%. 2-month treatment with either MNA or perindopril resulted in the reversal of impaired Ach-induced response to vasodilatation (4.5 and 5.5%, respectively) and a decrease in endothelial permeability (by about 60% for MNA-, as well as perindopril-treated mice). Improvement of endothelial function by MNA and perindopril was in both cases associated with the activation of ACE2/Ang-(1-7) and the inhibition of ACE/Ang II axes as evidenced by an approximately twofold increase in Ang-(1-9) and Ang-(1-7) and a proportional decrease in Ang II and its active metabolites. Finally, MNA and perindopril treatment resulted in an increase in L-arginine/ADMA ratio by 107% (MNA) and 140% (perindopril), as compared to non-treated mice. Functional and biochemical endothelial profiling in ApoE/LDLR-/- mice in vivo revealed that 2-month treatment with MNA (100 mg/kg/day) displayed a similar profile of vasoprotective effect as 2-month treatment with perindopril (10 mg/kg/day): i.e., the improvement in endothelial function that was associated with the beneficial changes in ACE/Ang II-ACE2/Ang (1-7) balance and in L-arginine/ADMA ratio in plasma. | Müller F, Pontones CA, Renner B, Mieth M, Hoier E, Auge D, Maas R, Zolk O, Fromm MF (2015)
N(1)-methylnicotinamide as an endogenous probe for drug interactions by renal cation transporters: studies on the metformin-trimethoprim interaction.
European journal of clinical pharmacology 71, 85-94 [PubMed:25552403]
[show Abstract]
PurposeN(1)-methylnicotinamide (NMN) was proposed as an in vivo probe for drug interactions involving renal cation transporters, which, for example, transport the oral antidiabetic drug metformin, based on a study with the inhibitor pyrimethamine. The role of NMN for predicting other interactions with involvement of renal cation transporters (organic cation transporter 2, OCT2; multidrug and toxin extrusion proteins 1 and 2-K, MATE1 and MATE2-K) is unclear.MethodsWe determined inhibition of metformin or NMN transport by trimethoprim using cell lines expressing OCT2, MATE1, or MATE2-K. Moreover, a randomized, open-label, two-phase crossover study was performed in 12 healthy volunteers. In each phase, 850 mg metformin hydrochloride was administered p.o. in the evening of day 4 and in the morning of day 5. In phase B, 200 mg trimethoprim was administered additionally p.o. twice daily for 5 days. Metformin pharmacokinetics and effects (measured by OGTT) and NMN pharmacokinetics were determined.ResultsTrimethoprim inhibited metformin transport with K i values of 27.2, 6.3, and 28.9 μM and NMN transport with IC50 values of 133.9, 29.1, and 0.61 μM for OCT2, MATE1, and MATE2-K, respectively. In the clinical study, trimethoprim increased metformin area under the plasma concentration-time curve (AUC) by 29.5 % and decreased metformin and NMN renal clearances by 26.4 and 19.9 %, respectively (p ≤ 0.01). Moreover, decreases of NMN and metformin renal clearances due to trimethoprim correlated significantly (r S=0.727, p=0.010).ConclusionsThese data on the metformin-trimethoprim interaction support the potential utility of N(1)-methylnicotinamide as an endogenous probe for renal drug-drug interactions with involvement of renal cation transporters. | Przyborowski K, Wojewoda M, Sitek B, Zakrzewska A, Kij A, Wandzel K, Zoladz JA, Chlopicki S (2015)
Effects of 1-Methylnicotinamide (MNA) on Exercise Capacity and Endothelial Response in Diabetic Mice.
PloS one 10, e0130908 [PubMed:26115505]
[show Abstract]
1-Methylnicotinamide (MNA), which was initially considered to be a biologically inactive endogenous metabolite of nicotinamide, has emerged as an anti-thrombotic and anti-inflammatory agent with the capacity to release prostacyclin (PGI2). In the present study, we characterized the effects of MNA on exercise capacity and the endothelial response to exercise in diabetic mice. Eight-week-old db/db mice were untreated or treated with MNA for 4 weeks (100 mg·kg-1), and their exercise capacity as well as NO- and PGI2-dependent response to endurance running were subsequently assessed. MNA treatment of db/db mice resulted in four-fold and three-fold elevation of urine concentrations of MNA and its metabolites (Met-2PY + Met-4PY), respectively (P<0.01), but did not affect HbA1c concentration, fasting glucose concentration or lipid profile. However, insulin sensitivity was improved (P<0.01). In MNA-treated db/db mice, the time to fatigue for endurance exercise was significantly prolonged (P<0.05). Post-exercise Δ6-keto-PGF1α (difference between mean concentration in the sedentary and exercised groups) tended to increase, and post-exercise leukocytosis was substantially reduced in MNA-treated animals. In turn, the post-exercise fall in plasma concentration of nitrate was not affected by MNA. In conclusion, we demonstrated for the first time that MNA improves endurance exercise capacity in mice with diabetes, and may also decrease the cardiovascular risk of exercise. | Liu M, Li L, Chu J, Zhu B, Zhang Q, Yin X, Jiang W, Dai G, Ju W, Wang Z, Yang Q, Fang Z (2015)
Serum N(1)-Methylnicotinamide Is Associated With Obesity and Diabetes in Chinese.
The Journal of clinical endocrinology and metabolism 100, 3112-3117 [PubMed:26066674]
[show Abstract]
ContextNicotinamide N-methyltransferase (NNMT) is a novel histone methylation modulator that regulates energy metabolism, and NNMT knockdown prevents diet-induced obesity in mice. However, whether NNMT plays a role in human obesity and type 2 diabetes (T2DM) remains to be elucidated.ObjectiveNNMT catalyzes methylation of nicotinamide to generate N(1)-methylnicotinamide (me-NAM). We aimed to investigate the associations of serum me-NAM with obesity and T2DM in Chinese.Design, setting, and participantsThe study subjects (n = 1160) were recruited from Dali, a city of Yunnan Province, in southwest China. Anthropometric phenotypes, fasting glucose, and serum lipids were measured. Serum me-NAM was measured by liquid chromatography-mass spectrometry.ResultsSerum me-NAM was positively correlated with body mass index and waist circumference and negatively with high-density lipoprotein (P ≤ .03). The correlations remained highly significant in the multivariate adjusted correlation analyses. In men (n = 691), positive correlations between me-NAM and fasting glucose, low-density lipoprotein, liver function, and serum creatinine levels were also observed in both simple and multivariate adjusted correlation analyses. In multiple logistic regression analyses, elevated serum me-NAM was associated with higher risks for overweight/obesity (odds ratios, 2.36 and 5.78; 95% confidence intervals, 1.10-5.08 and 1.78-18.76 for men and women, respectively; P ≤ .03) and diabetes (odds ratios, 1.56 and 1.86; 95% confidence intervals, 1.10-2.22 and 1.05-3.31 for men and women, respectively; P ≤ .03).ConclusionsThis first large-scale population study shows that me-NAM, as an indicator of NNMT activity, is strongly associated with obesity and diabetes, supporting NNMT as a potential target for treating obesity and diabetes in humans. | Nobuoka Y, Ogawa R, Echizen H (2014)
Simultaneous determination of N(1)-methylnicotinamide, L-carnitine, and creatinine in human plasma and urine by liquid chromatography with mass spectrometry for assessing the activities of multiple renal cationic transporters.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 967, 240-244 [PubMed:25129409]
[show Abstract]
Organic cation transporters are responsible for the disposition of various endogenous and therapeutic agents in humans; thus, there is a great need for the development of a simple assay for simultaneous assessment of the activities of multiple transporters. Using liquid chromatography-mass spectrometry (LC/MS), we developed an assay that allows for simultaneous quantitation of plasma and urinary levels of N(1)-methylnicotinamide (a substrate of hOCT2/hMATEs), L-carnitine (a substrate of hOCTN2), and creatinine (an indicator of glomerular filtration). Samples were diluted with ultrapure water, deproteinized with trichloroacetic acid, filtered, and then injected on a cation exchange column. The analytes were separated with a gradient LC technique and detected by MS. The total assay time was less than 8 min. The lower detection limits for N(1)-methylnicotinamide, L-carnitine, and creatinine were 2, 10, and 24 ng/mL, respectively. Recovery of the analytes was almost complete. A preliminary clinical study conducted in 25 healthy subjects revealed that the mean±SD for the renal clearance (CLR) of N(1)-methylnicotinamide (272.7±81.0 mL/min) far exceeded the glomerular filtration rate (116.3±19.6 mL/min), indicating the involvement of active tubular secretion, while the mean CLR of clearance of L-carnitine was close to nil (1.5±1.4 mL/min), indicating almost complete tubular reabsorption. The present method is potentially useful for clinical studies on the genetic control of cationic transporter activities and the transporter-mediated drug interactions. | Jacobs DM, Spiesser L, Garnier M, de Roo N, van Dorsten F, Hollebrands B, van Velzen E, Draijer R, van Duynhoven J (2012)
SPE-NMR metabolite sub-profiling of urine.
Analytical and bioanalytical chemistry 404, 2349-2361 [PubMed:22932811]
[show Abstract]
NMR-based metabolite profiling of urine is a fast and reproducible method for detection of numerous metabolites with diverse chemical properties. However, signal overlap in the (1)H NMR profiles of human urine may hamper quantification and identification of metabolites. Therefore, a new method has been developed using automated solid-phase extraction (SPE) combined with NMR metabolite profiling. SPE-NMR of urine resulted in three fractions with complementary and reproducible sub-profiles. The sub-profile from the wash fraction (100 % water) contained polar metabolites; that from the first eluted fraction (10 % methanol-90 % water) semi-polar metabolites; and that from the second eluted fraction (100 % methanol) aromatic metabolites. The method was validated by analysis of urine samples collected from a crossover human nutritional intervention trial in which healthy volunteers consumed capsules containing a polyphenol-rich mixture of red wine and grape juice extract (WGM), the same polyphenol mixture dissolved in a soy drink (WGM_Soy), or a placebo (PLA), over a period of five days. Consumption of WGM clearly increased urinary excretion of 4-hydroxyhippuric acid, hippuric acid, 3-hydroxyphenylacetic acid, homovanillic acid, and 3-(3-hydroxyphenyl)-3-hydroxypropionic acid. However, there was no difference between the excreted amounts of these metabolites after consumption of WGM or WGM_Soy, indicating that the soy drink is a suitable carrier for WGM polyphenols. Interestingly, WGM_Soy induced a significant increase in excretion of cis-aconitate compared with WGM and PLA, suggesting a higher demand on the tricarboxylic acid cycle. In conclusion, SPE-NMR metabolite sub-profiling is a reliable and improved method for quantification and identification of metabolites in urine to discover dietary effects and markers of phytochemical exposure. | Roux A, Xu Y, Heilier JF, Olivier MF, Ezan E, Tabet JC, Junot C (2012)
Annotation of the human adult urinary metabolome and metabolite identification using ultra high performance liquid chromatography coupled to a linear quadrupole ion trap-Orbitrap mass spectrometer.
Analytical chemistry 84, 6429-6437 [PubMed:22770225]
[show Abstract]
Metabolic profiles of biofluids obtained by atmospheric pressure ionization mass spectrometry-based technologies contain hundreds to thousands of features, most of them remaining unknown or at least not characterized in analytical systems. We report here on the annotation of the human adult urinary metabolome and metabolite identification from electrospray ionization mass spectrometry (ESI-MS)-based metabolomics data sets. Features of biological interest were first of all annotated using the ESI-MS database of the laboratory. They were also grouped, thanks to software tools, and annotated using public databases. Metabolite identification was achieved using two complementary approaches: (i) formal identification by matching chromatographic retention times, mass spectra, and also product ion spectra (if required) of metabolites to be characterized in biological data sets to those of reference compounds and (ii) putative identification from biological data thanks to MS/MS experiments for metabolites not available in our chemical library. By these means, 384 metabolites corresponding to 1484 annotated features (659 in negative ion mode and 825 in positive ion mode) were characterized in human urine samples. Of these metabolites, 192 and 66 were formally and putatively identified, respectively, and 54 are reported in human urine for the first time. These lists of features could be used by other laboratories to annotate their ESI-MS metabolomics data sets. | Watała C, Kaźmierczak P, Dobaczewski M, Przygodzki T, Bartuś M, Łomnicka M, Słomińska EM, Durackova Z, Chłopicki S (2009)
Anti-diabetic effects of 1-methylnicotinamide (MNA) in streptozocin-induced diabetes in rats.
Pharmacological reports : PR 61, 86-98 [PubMed:19307696]
[show Abstract]
1-Methylnicotinamide (MNA), a major endogenous metabolite of nicotinamide, possesses anti-thrombotic and anti-inflammatory activity, and reverses endothelial dysfunction. In the present work, we investigated whether such a vasoprotective profile of MNA activity affords anti-diabetic action in rats. Diabetes was induced by streptozotocin (STZ) in Sprague-Dawley rats. Eight weeks after STZ injection in untreated or MNA-treated rats (100 mg kg(-1) daily), development of diabetes (plasma concentrations of fasting and non-fasting glucose, HbA(1c), peptide C), development of oxidant stress (lipid peroxidation, carbonylation of plasma proteins), as well as NO-dependent endothelial function in aorta, coronary and mesenteric vessels were analyzed. Finally, the effect of chronic treatment with MNA on long-term survival of diabetic rats was determined. Chronic treatment with MNA profoundly lowered fasting glucose concentrations in plasma, displayed mild effects on plasma HbA(1c) and peptide C concentrations, while having no effects on non-fasting glucose. On the other hand, MNA treatment considerably lowered lipid peroxidation, protein carbonylation, completely prevented impairment of endothelium-dependent vasodilatation in the aorta that was mediated entirely by NO, but failed to affect endothelial function in resistant vessels, which was mediated only partially by NO. Most importantly, chronic treatment with MNA prolonged the long-term survival of diabetic rats. In conclusion, MNA displayed a significant anti-diabetic effect that may be linked to its vasoprotective activity. | Biedroń R, Ciszek M, Tokarczyk M, Bobek M, Kurnyta M, Słominska EM, Smoleński RT, Marcinkiewicz J (2008)
1-Methylnicotinamide and nicotinamide: two related anti-inflammatory agents that differentially affect the functions of activated macrophages.
Archivum immunologiae et therapiae experimentalis 56, 127-134 [PubMed:18373238]
[show Abstract]
Introduction1-Methylnicotinamide (MNA), a major metabolite of nicotinamide (NA), is known to exert anti-inflammatory effects in vivo. Treatment of inflammatory skin diseases by topical application of MNA provides certain advantages over the use of NA. However, in contrast to NA, the molecular mechanisms of the anti-inflammatory properties of MNA are not well known. In this study the influence of exogenous MNA and NA in vivo on the generation of inflammatory mediators by macrophages (Mvarphi) was investigated.Materials and methodsPeritoneal Mvarphi of CBA/J mice were activated in vitro with lipopolysaccharide and incubated with MNA or NA. The effect of these compounds on biological functions of Mvarphi was measured by evaluation of the production of reactive oxygen species (ROS) by luminol-dependent chemiluminescence, cytokines and prostaglandin E(2) (PGE(2)) by ELISA, and nitric oxide (NO) by the Griess method. Moreover, the expressions of inducible NO synthase and cyclooxygenase-2 were measured by Western blotting.ResultsIt was shown that at non-cytotoxic concentrations, NA inhibits the production of a variety of pro-inflammatory agents, such as tumor necrosis factor alpha, interleukin 6, NO, PGE(2), and the generation of ROS. In contrast to NA, exogenous MNA inhibited only the generation of ROS, while its effect on the synthesis of other mediators was negligible.ConclusionsThese results indicate that the anti-inflammatory properties of MNA demonstrated previously in vivo do not depend on its capacity to suppress the functions of immune cells, but more likely may be related to its action on vascular endothelium. The authors suggest that the limited permeability for exogenous MNA, in contrast to that for NA, may be responsible for its lack of suppressor activity against Mvarphi. | Dragun P, Makarewicz D, Wójcik L, Ziemka-Nałecz M, Słomka M, Zalewska T (2008)
Matrix metaloproteinases activity during the evolution of hypoxic-ischemic brain damage in the immature rat. The effect of 1-methylnicotinamide (MNA).
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 59, 441-455 [PubMed:18953089]
[show Abstract]
Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade the extracellular matrix and carry out key functions during brain development. Apart from a physiological role, excessive activation of MMPs in brain tissue has been postulated to represent a pathway for cell death arising from ischemia. To evaluate the possible involvement of MMPs in the perinatal brain asphyxia, we exposed 7-day-old rats to hypoxia-ischemia (HI). Unilateral HI was administered by ligation of the common carotid artery followed by hypoxia (7.4% O2/92.6% N2) for 65 minutes. This insult is known to produce brain damage confined to the cerebral hemisphere ipsilateral to the arterial occlusion in > 90% of animals. HI resulted in a significant elevation of MMP-2 and MMP-9 activity in the ipsilateral forebrain. The maximum activation was found at 48 hours and 7-14 days after the insult. These results suggest that early and late induction of MMPs may play a role in neuronal death as well as in repair processes. The treatment of animals subjected to HI with 1-methylnicotinamide (MNA), the anti-inflammatory agent, led to the inhibition of MMP-9 in an acute phase of ischemic damage and to the activation of MMP-2 in the later stages after injury. The timing of MMPs modulation by MNA may indicate its possible therapeutic implications. | 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, 230-239 [PubMed:17641676]
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Background and purpose1-methylnicotinamide (MNA) has been considered to be an inactive metabolite of nicotinamide. Here we assessed the anti-thrombotic activity of MNA in vivo.Experimental approachAntithrombotic action of MNA was studied in normotensive rats with extracorporeal thrombus formation (thrombolysis), in renovascular hypertensive rats with intraarterial thrombus formation (arterial thrombosis) and in a venous thrombosis model in rats (venous thrombosis).Key resultsMNA (3-100 mg kg(-1)) induced a dose-dependent and sustained thrombolytic response, associated with a rise in 6-keto-PGF(1alpha) in blood. Various compounds structurally related to MNA were either inactive or weaker thrombolytics. Rofecoxib (0.01-1 mg kg(-1)), dose-dependently inhibited the thrombolytic response of MNA, indomethacin (5 mg kg(-1)) abolished it, while L-NAME (5 mg kg(-1)) were without effect. MNA (3-30 mg kg(-1)) also reduced arterial thrombosis and this effect was abrogated by indomethacin (2.5 mg kg(-1)) as well as by rofecoxib (1 mg kg(-1)). MNA, however, did not affect venous thrombosis. In vitro MNA did not modify platelet aggregation nor induce vasodilation.Conclusions and implicationsMNA displayed a profile of anti-thrombotic activity in vivo that surpasses that of closely related compounds. MNA inhibited platelet-dependent thrombosis by a mechanism involving cyclooxygenase-2 and prostacyclin. Our findings suggest that endogenous MNA, produced in the liver by nicotinamide N-methyltransferase, could be an endogenous activator of prostacyclin production and thus may regulate thrombotic as well as inflammatory processes in the cardiovascular system. | Kuykendall JR, Cox R, Kinder D (2007)
1-Methylnicotinamide stimulates cell growth and inhibits hemoglobin synthesis in differentiating murine erythroleukemia cells.
Toxicology in vitro : an international journal published in association with BIBRA 21, 1656-1662 [PubMed:17826027]
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Exposure of murine erythroleukemia cells (MELCs) to nicotinamide (NA) or its synthetic analog N'-methylnicotinamide (N'-MN) reduces cell growth and induces terminal differentiation, marked by increased heme and globin accumulation. On the contrary, 1-methylnicotinamide (1-MN), the primary metabolite of excess NA, was found to stimulate cell growth and reduce spontaneous differentiation of cultured MELCs. Log phase MELCs exhibited up to 50% higher cell density above untreated cells when cultured for up to 96 h with 2.5 mM 1-MN. When combined with NA or several chemically-unrelated inducers of hemoglobin synthesis in cultured MELCs, 1-MN reduced the globin mRNA levels and heme accumulation by 40-80%. 1-MN was able to inhibit heme production if present during only the first 24-48 h after NA exposure. Pre-treatment with 1-MN could not confer resistance of cells to effects of NA, suggesting the inhibition is reversible. Commitment to differentiate in semisolid medium by the most potent inducer, 5mM N'-MN, was inhibited up to 95% by 2.5mM concentrations of 1-MN. It appears that 1-MN has opposing effects on growth and induction of differentiation than those seen in MELC cultures exposed to NA or N'-MN. | Wozniacka A, Wieczorkowska M, Gebicki J, Sysa-Jedrzejowska A (2005)
Topical application of 1-methylnicotinamide in the treatment of rosacea: a pilot study.
Clinical and experimental dermatology 30, 632-635 [PubMed:16197374]
[show Abstract]
Rosacea is a chronic facial dermatosis with a progressive course, which is characterized by the presence of erythema, papules, pustules, telangiectasias and sebaceous gland hyperplasia. However, the aetiology is still unknown; genetic predisposition, gastrointestinal disorders (Helicobacter pylori), infestations with Demodex folliculorum and environmental stimuli are considered to be involved in the inflammatory process. A metabolite of nicotinamide, 1-methylnicotinamide (MNA(+)), has anti-inflammatory properties, and this is the first study to test the effectiveness of this agent in treating rosacea. In total, 34 patients with rosacea were treated with a gel containing 0.25% MNA(+) as a chloride salt, twice daily for 4 weeks, after which improvement was observed in 26/34 cases. The improvement was good in 9/34 and moderate in 17/34, but no clinical effect was noted in seven subjects. In only one case was skin irritation given as the reason for treatment withdrawal. These results indicate that MNA(+) might be a useful agent for treating rosacea. | Ohdoi C, Nyhan WL, Kuhara T (2003)
Chemical diagnosis of Lesch-Nyhan syndrome using gas chromatography-mass spectrometry detection.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 792, 123-130 [PubMed:12829005]
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Lesch-Nyhan syndrome (LNS) is caused by a severe deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) and clinically characterized by self-injurious behavior and nephrolithiasis; the latter is treatable with allopurinol, an inhibitor of xanthine oxidase which converts xanthine and hypoxanthine into uric acid. In the HPRT gene, more than 200 different mutations are known, and de novo mutation occurs at a high rate. Thus, there is a great need to develop a highly specific method to detect patients with HPRT dysfunction by quantifying the metabolites related to this enzyme. A simplified urease pretreatment of urine, gas chromatography-mass spectrometry, and stable isotope dilution method, developed for cutting-edge metabonomics, was further applied to quantify hypoxanthine, xanthine, urate, guanine and adenine in 100 microl or less urine or eluate from filter-paper-urine strips by additional use of stable isotope labeled guanine and adenine as the internal standards. In this procedure, the recoveries were above 93% and linearities (r(2)=0.9947-1.000) and CV values (below 7%) of the indicators were satisfactory. In four patients with proven LNS, hypoxanthine was elevated to 8.4-9.0 SD above the normal mean, xanthine to 4-6 SD above the normal mean, guanine to 1.9-3.7 SD, and adenine was decreased. Because of the allopurinol treatment for all the four patients, their level of urate was not elevated, orotate increased, and uracil was unchanged as compared with the control value. It was concluded that even in the presence of treatment with allopurinol, patients with LNS can be chemically diagnosed by this procedure. Abnormality in the levels of hypoxanthine and xanthine was quite prominent and n, the number of standard deviations above the normal mean, combined for the two, was above 12.9. | Gebicki J, Sysa-Jedrzejowska A, Adamus J, Woźniacka A, Rybak M, Zielonka J (2003)
1-Methylnicotinamide: a potent anti-inflammatory agent of vitamin origin.
Polish journal of pharmacology 55, 109-112 [PubMed:12856834]
[show Abstract]
It has been found that 1-methylnicotinamide (MNA+), a metabolite of nicotinamide, possesses significant anti-inflammatory properties. MNA+ is chemically stable, non-toxic and well tolerated. MNA+ can be used to treat wide variety of diseases and disorders and the use of this compound provides certain advantages over the use of nicotinamide. | Slominska EM, Smolenski RT, Szolkiewicz M, Leaver N, Rutkowski B, Simmonds HA, Swierczynski J (2002)
Accumulation of plasma N-methyl-2-pyridone-5-carboxamide in patients with chronic renal failure.
Molecular and cellular biochemistry 231, 83-88 [PubMed:11952169]
[show Abstract]
Intracellular catabolism of NAD in mammalian cells occurs mainly via reaction catalyzed by poly(ADP-ribose) polymerase (PARP) with the release of nicotinamide, which is then metabolized predominantly to N-methyl-2-pyridone-5-carboxamide (2PY). PARP could be activated by binding to broken DNA and is known to be involved in DNA repair mechanisms, cell stress response and regulation of apoptosis. 2PY may accumulate under disease conditions resulting in accelerated DNA damage and retention of catabolic products. Our hypothesis was that chronic renal failure would lead to elevation of 2PY and potentially to inhibition of PARP and related physiological mechanisms. In the present study we: (a) compared plasma 2PY concentration in healthy subjects and in patients with chronic renal failure (CRF); (b) evaluated the relationship between plasma 2PY concentration and the severity of CRF; (c) evaluated the effect of hemodialysis treatment and kidney transplantation on 2PY concentration. We found that the plasma 2PY concentration in healthy subjects is 0.83+/-0.18 microM but it could increase up to 40 microM in patients with CRF. A significant correlation was found in CRF between plasma 2PY and creatinine concentration. A single hemodialysis treatment was associated with significant reduction of plasma 2PY concentration after the hemodialysis, but it increased rapidly 48 h after the end of treatment. Successful kidney transplantation was associated with return of 2PY concentration to the normal range. In conclusion, our results indicated significant production of 2PY in humans. In healthy subjects 2PY is cleared from the plasma by excretion in the urine. Altered excretion by the kidney leads to increase in plasma concentration of 2PY. It is possible that 2PY may play a significant role in the development of uremic toxemia, especially as an inhibitor of poly(ADP-ribose)polymerase. | Musfeld C, Biollaz J, Bélaz N, Kesselring UW, Decosterd LA (2001)
Validation of an HPLC method for the determination of urinary and plasma levels of N1-methylnicotinamide, an endogenous marker of renal cationic transport and plasma flow.
Journal of pharmaceutical and biomedical analysis 24, 391-404 [PubMed:11199218]
[show Abstract]
N1-Methylnicotinamide (NMN) is an endogenous cationic metabolite of nicotinamide (niacine, vitamine PP) whose renal clearance reflects both the capacity of the renal tubular transport system to secrete organic cations and renal plasma flow. NMN is present in human plasma and urine at the 1-117-ng ml(-1) and 0.5-25-microg ml(-1) concentration range, respectively, and its level depends notably on pathophysiological (age, renal or hepatic diseases) conditions. We report the optimization and validation of an HPLC method for the measurement of endogenous NMN in biological fluids after derivatization into a fluorescent compound. Plasma is first deproteinized with TCA 20% and the urine diluted 1:10 with HCI 10(-4) M prior to the derivatization procedure, which includes a condensation reaction of NMN with acetophenone in NaOH at 0 degrees C, followed by dehydration in formic acid and subsequent formation of the fluorescent 1,6-naphthyridine derivatives after heating samples in a boiling water bath. The synthetic homologous derivative N1-ethylnicotinamide (NEN) reacts similarly and is added as internal standard into the biological fluid. The reaction mixture is subjected to reverse phase high performance liquid chromatography on a Nucleosil 100-C18 column using a mobile phase (acetonitrile 22%, triethylamine 0.5%, 0.01 M sodium heptanesulfonate adjusted to pH 3.2), delivered isocratically at a flow rate of 1 ml min(-1), NMN and NEN are detected at 7.8 and 10 min by spectrofluorimetry with excitation and emission wavelengths set at 366 and 418 nm, respectively. The addition-calibration method is used with plasma and urine pools. Calibration curves (using the internal standard method) are linear (r2 > 0.997) at concentrations up to 109 ng ml(-1) and 15.7 microg ml(-1) in plasma and urine, respectively. Both intra- and inter-assay precision of plasma control samples at 10, 50 and 90 ng ml(-1) were lower than 3.3% and concentrations not deviating more than 2.7% from their nominal values. In urine intra- and inter-assay CVs of control samples at 1, 5 and 9 microg ml(-1) are lower than 8.3%, with concentrations not deviating more than -9.0 to +11.8% from their nominal values. This analytical method has therefore the required sensitivity and selectivity to measure NMN in plasma and urine, enabling the non-invasive determination of the tubular secretory capacity of the kidney and the renal plasma flow. | Orlando R, Floreani M, Napoli E, Padrini R, Palatini P (2000)
Renal clearance of N(1)-methylnicotinamide: a sensitive marker of the severity of liver dysfunction in cirrhosis.
Nephron 84, 32-39 [PubMed:10644906]
[show Abstract]
Background/aimsData have appeared suggesting that an impairment of renal tubular secretion is present in liver cirrhosis, even in the absence of a clinically evident renal dysfunction. To address this question, we evaluated the renal clearance of N(1)-methylnicotinamide (NMN), a marker of the renal secretory function, in healthy subjects and patients with liver cirrhosis of increasing severity, but with a normal glomerular filtration rate.MethodsThe renal clearances of endogenous NMN, inulin, and creatinine were measured in 14 normal subjects and in two groups of age-matched cirrhotic patients (10 Child A and 10 Child C). In 6 subjects, 2 per group, the concentration dependence of the NMN clearance was also studied, following an oral nicotinamide load.ResultsContrary to expectations, the renal NMN clearance increased in cirrhotic patients, in relation to the severity of liver disease (r = 0.83 with Pugh's score; p < 0.001). The NMN-to-inulin clearance ratio increased from a control value of 2.2 +/- (SD) 0.4 to 3.1 +/- 0.2 and 5.2 +/- 0.9 in Child A and Child C cirrhotics, respectively (p < 0.001 for all comparisons), indicating that NMN was completely cleared from plasma in the latter patients. Consistently, the analysis of the concentration dependence of the renal NMN clearance revealed the presence of a carrier-mediated reabsorption which apparently was no longer operating in the decompensated patients. Discriminant analysis showed that renal NMN clearance, and NMN-to-creatinine and NMN-to-inulin clearance ratios could all distinguish between the three study groups, with sensitivities and specificities equal or greater than 90%.ConclusionsContrary to previous proposals, NMN is not a probe of general validity for renal tubular secretion. In particular, due to an imbalance between secretion and reabsorption, its renal clearance in liver cirrhosis cannot be used to determine the degree of tubular secretion of which an individual is capable. However, renal NMN clearance appears to be a very sensitive marker of the severity of liver dysfunction in cirrhosis. The potentialities of this renal parameter as a diagnostic and prognostic test in liver cirrhosis deserve further study. | Carter EG (1982)
Quantitation of urinary niacin metabolites by reversed-phase liquid chromatography.
The American journal of clinical nutrition 36, 926-930 [PubMed:6215856]
[show Abstract]
The niacin metabolites N1-methyl-2-pyridone-5-carboxamide (2-PYR) and N1-methylnicotinamide (N-MN) have been quantified in human urine using isocratic reversed-phase high-performance liquid chromatography with ultraviolet detection after a simple anion-exchange clean-up procedure. The coefficients of variation (%) of the method for 2-PYR and N-MN were 6.3 and 6.8, respectively, and the limits of detection (mg/1 urine) were 0.05 for 2-PYR and 0.20 for N-MN. Results by this method compared favorably with those obtained by established techniques. It is a straight forward, rapid, and sensitive procedure for the assessment of niacin status. | Patterson JI, Brown RR, Linkswiler H, Harper AE (1980)
Excretion of tryptophan-niacin metabolites by young men: effects of tryptophan, leucine, and vitamin B6 intakes.
The American journal of clinical nutrition 33, 2157-2167 [PubMed:6448542]
[show Abstract]
Three human metabolic studies, each 35 days in length, were performed to investigate the relationship between tryptophan intake and the proportion of dietary tryptophan converted to niacin and the effect of supplements of L-leucine and vitamin B6 on this conversion. Nine college men consumed a basal diet that provided 8 mg of niacin, 1 mg of vitamin B6, and either 245, 548, or 845 mg of tryptophan from proteins per day. During each 35-day study, for one 15-day period basal diet alone was consumed, for another 15-day period basal diet plus 10 g of L-leucine per day was consumed, and for the last 5-day period, 20 mg of vitamin B6 per day was added to the diets of both groups. N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, and quinolinic acid were measured in 24-hr urine samples. There were no significant or consistent effects of L-leucine or vitamin B6 supplements on the excretin of any of the metabolites measured. The proportion of tryptophan converted to niacin tended to increase as tryptophan consumption increased; however, this change was small and was probably not significant over the range of tryptophan intakes studied. The average conversion ration of tryptophan to niacin was approximately 72:1 in these subjects. | Shaikh B, Pontzer NJ (1979)
Direct urinary assay method for N1-methylnicotinamide by soap chromatography.
Journal of chromatography 162, 596-600 [PubMed:160917] | Pelletier O, Brassard R (1977)
Automated and manual determination of N1-methylnicotinamide in urine.
The American journal of clinical nutrition 30, 2108-2116 [PubMed:145178]
[show Abstract]
An automated AutoAnalyzer method and a manual adaptation of the automated method are described for determining N1-methylnicotinamide (NMN) in urine. The new methods incorporate improvements presented by Pelletier and Campbell (Anal. Biochem. 3:60, 1962) for the fluorometric determination of NMN after condensation with methyl ethyl ketone (MEK). The new methods are simpler and not limited by the usage of a single brand of MEK. Various brands of MEK into which hydrogen peroxide had been added in order to catalyze the formation of the condensation product were used and found to give comparable NMN values with different urine specimens. Results of the analysis of 21 urine specimens by the new procedures agreed well with those by the method of Carpenter and Kodicek (Biochem. J. 46: 421, 1950) for which interpretation guidelines exist. Furthermore, it was found that eluates from the chromatographic purification of thiamine in urine with Decalso retained the NMN present in the original specimens, gave complete recoveries of added NMN and were free from nearly all interfering fluorescing substances; this purification would be advantageous for determining with accuracy and precision NMN levels in the urine of deficient subjects and could be used routinely when thiamine analysis has to be performed. |
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