NNMT transfers CH3 from SAM to NAM to form MNA

Stable Identifier
R-HSA-5359451
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Nicotinamide N-methyltransferase (NNMT) is a cytosolic protein which catalyses the N-methylation of nicotinamide (NAM aka vitamin B3) and other pyridines (Aksoy et al. 1994, 1995). It is mainly expressed in the liver and to a lesser extent in the kidney, lung, skeletal muscle, placenta and heart. NAM is a precursor for NAD+, an important cofactor in cellular redox states and energy metabolism. NNMT methylates NAM using S-adenosylmethionine (SAM) as the methyl donor to form 1-methylnicotinamide (MNA). Kraus et al. found Nnmt expression is increased in white adipose tissue and liver of obese and diabetic mice. An Nnmt knockdown stategy could protect against diet-induced obesity by increasing cellular energy expenditure thus could be a target for treating obesity and type 2 diabetes (Kraus et al. 2014). Experiments on rats with thrombolytic models suggest endogenous MNA could be a stimulator of the COX2/PGI2 pathway and thus regulate an anti-thrombotic effect (Chlopicki et al. 2007).

Literature References
PubMed ID Title Journal Year
8182091 Human liver nicotinamide N-methyltransferase. cDNA cloning, expression, and biochemical characterization

Aksoy, S, Szumlanski, CL, Weinshilboum, RM

J. Biol. Chem. 1994
17641676 1-Methylnicotinamide (MNA), a primary metabolite of nicotinamide, exerts anti-thrombotic activity mediated by a cyclooxygenase-2/prostacyclin pathway

Chlopicki, S, Swies, J, Mogielnicki, A, Buczko, W, Bartus, M, Lomnicka, M, Adamus, J, Gebicki, J

Br. J. Pharmacol. 2007
8575745 Human nicotinamide N-methyltransferase gene: molecular cloning, structural characterization and chromosomal localization

Aksoy, S, Brandriff, BF, Ward, A, Little, PF, Weinshilboum, RM

Genomics 1995
24717514 Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity

Kraus, D, Yang, Q, Kong, D, Banks, AS, Zhang, L, Rodgers, JT, Pirinen, E, Pulinilkunnil, TC, Gong, F, Wang, YC, Cen, Y, Sauve, AA, Asara, JM, Peroni, OD, Monia, BP, Bhanot, S, Alhonen, L, Puigserver, P, Kahn, BB

Nature 2014
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
nicotinamide N-methyltransferase activity of NNMT [cytosol]
Physical Entity
Activity
Orthologous Events
Cross References
Rhea
Authored
Reviewed
Created