2.1.1.1: nicotinamide N-methyltransferase
This is an abbreviated version!
For detailed information about nicotinamide N-methyltransferase, go to the full flat file.
Reaction
Synonyms
ANMT-1, B0303.2, methyltransferase, nicotinamide, nicotinamide N-methyl transferase, nicotinamide N-methyltransferase, NNMT
ECTree
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General Information
General Information on EC 2.1.1.1 - nicotinamide N-methyltransferase
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malfunction
metabolism
physiological function
additional information
malfunction
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alterations in in vivo enzyme NNMT activity are believed to be negatively associated with gene polymorphism and environmental influences are also considered to be significant
malfunction
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enzyme NNMT plays an important role in PANC-1 cell proliferation, metastatic potential and survival under metabolic stress. Enzyme silencing markedly reduces cell proliferation, whereas enzyme overexpression promotes cell growth moderately. Knockdown of NNMT also significantly suppresses the migration and invasion capacities of pancreatic cancer PANC-1 cells. Enzyme NNMT upregulation enhances cell migration and invasion capacities. In addition, NNMT knockdown cells are much less resistant to glucose deprivation and rapamycin as well as glycolytic inhibitor 2-deoxyglucose whereas NNMT-overexpressing cells show opposite effects although the effects are not so striking
malfunction
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nicotinamide N-methyltransferase overexpression is associated with Akt phosphorylation and indicates worse prognosis in patients with nasopharyngeal carcinoma
malfunction
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shRNA-mediated gene silencing of NNMT leads to a significntl inhibition of cell proliferation and colony formation ability, downregulation of the enzyme significantly reduces the tumorigenicity of A-549 cells
malfunction
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suppression of hepatic Nnmt expression in vivo alters glucose and cholesterol metabolism. Primary hepatocytes with Nnmt knockdown have significantly lower hepatocyte glucose output (50%) and significantly lower expression of genes encoding both catalytic glucose-6-phosphatase (20%) and cytosolic phosphoenolpyruvate carboxykinase 1 (40%) compared with control hepatocytes. In contrast, primary hepatocytes in which Nnmt is overexpressed have 1.4fold higher glucose output, threefold higher expression of glucose-6-phosphatase and fourfold higher expression of phosphoenolpyruvate carboxykinase compared with control hepatocytes
malfunction
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the enzyme effects on neurons are reduced in cells lacking epinephrin EFNB2 or Akt
malfunction
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suppression of hepatic Nnmt expression in vivo alters glucose and cholesterol metabolism. Primary hepatocytes with Nnmt knockdown have significantly lower hepatocyte glucose output (50%) and significantly lower expression of genes encoding both catalytic glucose-6-phosphatase (20%) and cytosolic phosphoenolpyruvate carboxykinase 1 (40%) compared with control hepatocytes. In contrast, primary hepatocytes in which Nnmt is overexpressed have 1.4fold higher glucose output, threefold higher expression of glucose-6-phosphatase and fourfold higher expression of phosphoenolpyruvate carboxykinase compared with control hepatocytes
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enzyme Nnmt regulates glucose and cholesterol metabolism. Sirt1 is required for the metabolic actions of the enzyme, which regulates Sirt1 stability
metabolism
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NNMTexpression is significantly positively associated with pAkt/protein kinase B expression
metabolism
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the effects of enzyme NNMT expression in SH-SY5Y cells, e.g. protection against the toxicity of the Complex I (CxI) inhibitors 1-methyl-4-phenylpyridinium ion and rotenone, are mediated via increased CxI activity and ATP production and the sequential activation of the epinephrin EFNB2 and Akt signalling pathways
metabolism
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enzyme Nnmt regulates glucose and cholesterol metabolism. Sirt1 is required for the metabolic actions of the enzyme, which regulates Sirt1 stability
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physiological function
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progression of vascular inflammation and atherosclerosis is associated with the upregulation of hepatic NNMT activity and subsequent increase in endogenous 1-methylnicotinamide plasma levels
physiological function
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the enzyme is involved in tumour differentiation in oral squamous cell carcinoma, overview
physiological function
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effect of enzyme NNMT expression on cell survival under metabolic stress, the enzyme promotes cell survival and growth and increases cell migration and invasion capacities , NNMT-expressing cells demonstrate enhanced resistance to rapamycin, phenotype, overview
physiological function
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expression of enzyme NNMT in enzyme-deficient SH-SY5Y human neuroblastoma cells significantly increases the expression of all three sirtuins, class III DNA deacetylase enzymes known to regulate mitochondrial energy production and cell cycle. Sirtuin 3 is a key mediator of NNMT-induced complex I activity and ATP synthesis. Central role for enzyme NNMT in the regulation of energy homeostasis
physiological function
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nicotinamide N-methyltransferase is a metabolic regulator in adipocytes and also regulates hepatic nutrient metabolism through Sirt1 protein stabilization, the metabolic effects of the enzyme in the liver are mediated by its product 1-methylnicotinamide. Nnmt is a positive regulator of gluconeogenesis in primary hepatocytes. Methylation of nicotinamide by Nnmt is a major pathway for the clearance of excess vitamin B3 from the body
physiological function
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nicotinamide N-methyltransferase is involved in the biotransformation and detoxification of many drugs and xenobiotic compounds, it enhances the capacity of tumorigenesis associated with the promotion of cell cycle progression in human colorectal cancer cells. The enzyme significantly accelerates cell proliferation, enhances colony formation in vitro and tumorigenicity in mice, and inhibits apoptosis, it promotes cell cycle progression, increases ATP and 1-methylnicotinamide level and decreases ROS levels. 1-Methylnicotinamide also accelerates cell growth, inhibits apoptosis, promotes cell cycle progression, attenuates ROS production and increases ATP levels. The enzyme may play a vital role in energy balance and ROS induction, 1-Methylnicotinamide is beneficial in conditions such as inflammation and antioxidation
physiological function
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role of nicotinamide N-methyltransferase in non-small cell lung cancer
physiological function
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the enzyme is overexpressed in many human cancers and is associated with poor prognosis. Enzyme NNMT might play a significant role in tumor progression and shorter survival time in patients with nasopharyngeal carcinoma, and it might promote the activation of MMP-2 via a pathway that sequentially involves pAkt signaling pathway
physiological function
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the enzyme NNMT expression protects against neurotoxin-mediated cell death by increasing Complex I (CxI) activity, resulting in increased ATP synthesis, mediated via protection of the NDUFS3 subunit of CxI from degradation by increased 1-methylnicotinamide production. The enzyme expression increases neurite branching and the presynaptic marker synaptophysin, synaptophysin expression is induced by the enzyme. 1-Methylnicotinamide replicates the effects of enzyme NNMT expression upon SH-SY5Y neurite branching, effects of NNMT expression on neuron morphology and differentiation, overview. Recombinant NNMT-V5 expression in SH-SY5Y cells changes cellular morphology and increases dopamine uptake and release. The effects of enzyme NNMT expression in SH-SY5Y cells, e.g. protection against the toxicity of the Complex I (CxI) inhibitors 1-methyl-4-phenylpyridinium ion and rotenone, are mediated via increased CxI activity and ATP production and the sequential activation of the epinephrin EFNB2 and Akt signalling pathways. The enzyme NNMT reduces cholinergic phenotype but does not induce terminal differentiation
physiological function
cells expressing NMMT are less sensitive to beta-carbolines such as norharman
physiological function
down-regulation of NNMT in colorectal cancer HT-29 cells diminishes 5-fluorouracil resistance, while overexpression of NNMT in SW-480 cells enhances it. NNMT reduces reactive oxygen species production induced by 5-fluorouracil by increasing 1-methylnicotinamide in colorectal cancer cells. The reduction in ROS leads to inactivation of the ASK1-p38 mitogen-activated protein kinase pathway, which reduces 5-fluorouracil-induced apoptosis. In nude mice implanted with colorectal cancer xenografts, NNMT attenuates 5-fluorouracil-induced inhibition of colorectal cancer tumor growth
physiological function
exposure of BEAS-2B cells to nickel increases histone H3K9 dimethylation (H3K9me2), suppresses the expressions of H3K9me2-associated genes MAP2K3 and DKK1, and induces NNMT repression at both the protein and mRNA levels. Over-expression of NNMT inhibits nickel-induced H3K9me2 and alters the cellular SAM/SAH ratio
physiological function
exposure of BEAS-2B cells to nickel increases histone H3K9 dimethylation, suppresses the expressions of H3K9me2-associated genes MAP2K3 and DKK1, and induces NNMT repression at both the protein and mRNA levels. Overexpression of NNMT inhibits nickel-induced H3K9me2 and alters the cellular SAM/SAH ratio
physiological function
Nnmt overexpression decreases S-adenosyl-L-methionine (SAM) levels and the SAM/S-adenosylhomocysteine (SAH) ratio both in vivo and in vitro. Nnmt knockdown does not change methyl donor balance in mouse primary hepatocytes but increases SAM levels and the SAM/SAH ratio when Gnmt, the dominantly expressed methyltransferase in liver, is simultaneously knocked down. Expression of enzymatically deficient Nnmt increases the SAM/SAH ratio. Proteins Bhmt, Mat1a, and Ahcy, components of the methionine cycle, interact with NNMT in liver. Mutant Nnmt increases the level of remethylation of homocysteine to SAM
physiological function
ortholog ANMT-1 competes with the methyltransferase LCMT-1 for methyl groups from S-adenosyl methionine. Thereby, it regulates the catalytic capacities of LCMT-1, targeting NPRL-2, a regulator of autophagy. During aging, high neuronal ANMT-1 activity induce autophagy via NPRL-2. In younger animals, ANMT-1 activity disturbs neuronal homeostasis and dopamine signaling, causing abnormal behavior
physiological function
shRNA-mediated downregulation of NNMT expression levels inhibits the proliferation and density?-ependent growth of SCC-12 cells. The migration and invasion ofSCC cells are markedly decreased in NNMT-nockdown cells. High NNMT expression levels are accompanied by high expression levels of EMT-ssociated genes, and NNMT knockdown effectively suppresses the expression of matrix metalloproteinase 9, osteopontin, versican core protein and zinc finger protein SNAI2 in SCC-12 cells
physiological function
the expression level of NNMT is elevated in the peripheral blood and tissues of patients with prostate cancer. The overexpression of NNMT enhances PC-3 cell viability, invasion and migration capacity. The overexpression of NNMT significantly increases the mRNA level of sirtuin 1 in PC-3 cells. Nicotinamide treatment significantly suppresses the expression of SIRT1 even in PC-3 cells transfected with adeno-associated virus-NNMT
physiological function
the expression of NNMT in the SH-SY5Y cell-line has no effect on cell death, viability, ATP content or mitochondrial membrane potential
physiological function
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progression of vascular inflammation and atherosclerosis is associated with the upregulation of hepatic NNMT activity and subsequent increase in endogenous 1-methylnicotinamide plasma levels
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physiological function
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nicotinamide N-methyltransferase is a metabolic regulator in adipocytes and also regulates hepatic nutrient metabolism through Sirt1 protein stabilization, the metabolic effects of the enzyme in the liver are mediated by its product 1-methylnicotinamide. Nnmt is a positive regulator of gluconeogenesis in primary hepatocytes. Methylation of nicotinamide by Nnmt is a major pathway for the clearance of excess vitamin B3 from the body
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in vitro overexpression of the enzyme has revealed many cytoprotective effects of NNMT, in particular increased complex I activity and ATP synthesis. siRNA-mediated silencing of sirtuin 3 expression decreases complex I activity in NNMT-expressing SH-SY5Y cells to that observed in wild-type SH-SY5Y, and significantly reduces cellular ATP content also
additional information
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nicotinamide and 1-methylnicotinamide are neurotoxic, chronic exposure to Mn2+ plays a role in idiopathic Parkinson's disease associated to 1-methylnicotinamide. But no metal-increased NNMT activity can be measured
additional information
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recombinant ectopic expression of NNMT in enzyme-deficient SH-SY5Y human neuroblastoma cells increased adenosine triphosphate synthesis and complex I activity, effects of which are replicated by the addition of 1-methylnicotinamide. The enzyme expression protects against the toxicity of mitochondrial toxins and abolishes the toxic effects of KCN, 2,4-dinitrophenol, and 6-hydroxydopamine, and reduced that of rotenone, while 1-methylnicotinamide significantly reduces the toxicity of rotenone, but has no effect on the toxicity of KCN, 2,4-dinitrophenol, and 6-hydroxydopamine. The enzyme is cytoprotective against toxins that inhibit various aspects of mitochondrial function, which are not mediated solely via increased 1-methylnicotinamide production, but in combination with other unidentified mechanisms