Information on EC 2.1.1.1 - nicotinamide N-methyltransferase

development and evaluation of a HPLC-UV method for measuring nicotinamide N-methyltransferase activity in biological samples, overview

additional information

NNMT uses a rapid equilibrium ordered mechanism, where NNMT first binds S-adenosyl-L-methionine, which is followed by nicotinamide. Methyl transfer occurs, and methylated nicotinamide and S-adenosylhomocysteine are released consecutively

additional information

additional information

development and evaluation of a HPLC-UV method for measuring nicotinamide N-methyltransferase activity in biological samples, overview

additional information

development and evaluation of a HPLC-UV method for measuring nicotinamide N-methyltransferase activity in biological samples, overview

additional information

enzyme may function in detoxificating of numerous alkaloids

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NATURAL SUBSTRATE

NATURAL PRODUCT

REACTION DIAGRAM

ORGANISM

UNIPROT

COMMENTARY
(Substrate)

LITERATURE
(Substrate)

COMMENTARY
(Product)

LITERATURE
(Product)

REVERSIBILITY
r=reversible
ir=irreversible
?=not specified

L-methionine + nicotinamide

L-homocysteine + 1-methylnicotinamide

Rattus norvegicus

441251

S-adenosyl-L-methionine + nicotinamide

S-adenosyl-L-homocysteine + 1-methylnicotinamide

5 entries

additional information

5 entries

S-adenosyl-L-methionine + nicotinamide

S-adenosyl-L-homocysteine + 1-methylnicotinamide

701990, 733214, 733279, 733614, 733618, 733625, 733636, 734104, 734368

S-adenosyl-L-methionine + nicotinamide

S-adenosyl-L-homocysteine + 1-methylnicotinamide

701990, 706094, 733737, 734368, 734757

S-adenosyl-L-methionine + nicotinamide

S-adenosyl-L-homocysteine + 1-methylnicotinamide

Mus musculus C57/BL6J

706094

S-adenosyl-L-methionine + nicotinamide

S-adenosyl-L-homocysteine + 1-methylnicotinamide

Mus musculus C57Bl6/J

734757

S-adenosyl-L-methionine + nicotinamide

S-adenosyl-L-homocysteine + 1-methylnicotinamide

additional information

NNMT catalyzes the N-methylation of nicotinamide and other structural analogs, and is involved in the biotransformation of many drugs and xenobiotic compounds

704775

additional information

development and evaluation of a HPLC-UV method for measuring nicotinamide N-methyltransferase activity in biological samples, overview

additional information

development and evaluation of a HPLC-UV method for measuring nicotinamide N-methyltransferase activity in biological samples, overview

additional information

development and evaluation of a HPLC-UV method for measuring nicotinamide N-methyltransferase activity in biological samples, overview

additional information

enzyme may function in detoxificating of numerous alkaloids

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COFACTOR

ORGANISM

UNIPROT

COMMENTARY

LITERATURE

IMAGE

S-adenosyl-L-methionine

S-adenosyl-L-methionine

701990, 706094, 733737, 734368, 734757

S-adenosyl-L-methionine

701990, 733214, 733279, 733614, 733618, 733625, 733636, 734104, 734368

S-adenosyl-L-methionine

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METALS and IONS

ORGANISM

UNIPROT

COMMENTARY

LITERATURE

additional information

no effect on enzyme activity by Fe2+ and Mn2+, but Mn2+ reduces mouse CD1 brain striatum neuronal cell survival with less than 10% cells surviving at 0.1 mM Mn2+

733737

show all columns Go to Inhibitor Search

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INHIBITOR

ORGANISM

UNIPROT

COMMENTARY

LITERATURE

IMAGE

1,3-dimethylquinolin-1-ium

1,4-dimethylquinolin-1-ium

1,5-dimethylquinolin-1-ium

1,8-dimethylquinolin-1-ium

1-ethyl-4-methylquinolin-1-ium

1-ethyl-6-fluoro-4-methylquinolin-1-ium

1-ethyl-8-methylquinolin-1-ium

1-methyl nicotinamide

1-methyl-3-(methylamino)quinolin-1-ium

1-methylnicotinamide

2-amino-1-methylquinolin-1-ium

3-(6-amino-6-oxohexyl)benzamide

inhibitor mimics the transition state of the methylation reaction

3-amino-1-methylquinolin-1-ium

3-amino-2-methylisoquinolin-2-ium

3-amino-6-fluoro-1-methylquinolin-1-ium

4-methyl-N'-methylnicotinamide

5'-([(3S)-3-amino-3-carboxypropyl][[3-(methoxycarbonyl)phenyl]methyl]amino)-5'-deoxyadenosine

5'-deoxy-5'-[[(3S)-3,4-diamino-4-oxobutyl][(naphthalen-2-yl)methyl]amino]adenosine

inhibitor demonstrates a dose-dependent inhibitory effect on the cell proliferation of the HSC-2 human oral cancer cell line

5'-deoxy-5'-[[(naphthalen-2-yl)methyl](propan-2-yl)amino]adenosine

5'-[(3-amino-3-carboxypropyl)[3-(3-carbamoyl-4-methylphenyl)prop-2-yn-1-yl]amino]-5'-deoxyadenosine

5'-[(3-amino-3-carboxypropyl)[3-(3-carbamoylphenyl)prop-2-yn-1-yl]amino]-5'-deoxyadenosine

compound exhibits around 1000fold selectivity for NNMT over other methyltransferases and almost 100fold selectivity for S-5'-adenosyl-L-homocysteine hydrolase

5'-[(3-amino-3-carboxypropyl)[3-(5-carbamoyl-2-methoxyphenyl)prop-2-yn-1-yl]amino]-5'-deoxyadenosine

5'-[(4-amino-4-oxobutyl)[(naphthalen-2-yl)methyl]amino]-5'-deoxyadenosine

5'-[(5-amino-5-oxopentyl)[(naphthalen-2-yl)methyl]amino]-5'-deoxyadenosine

5'-[[(3S)-3-amino-3-carboxypropyl][(3-carbamoylphenyl)methyl]amino]-5'-deoxyadenosine

5'-[[(3S)-3-amino-3-carboxypropyl][(3-carboxyphenyl)methyl]amino]-5'-deoxyadenosine

5'-[[(3S)-3-amino-3-carboxypropyl][4-(3-carbamoylphenyl)butyl]amino]-5'-deoxyadenosine

5-amino-1-methylquinolin-1-ium

5-[[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]-7-(3-carbamoylphenyl)hept-6-ynoic acid

log Ki value 4.65

6-(methylamino)pyridine-3-carboxamide

compound inhibits NNMT enzymatic activity and reduces the formation of 1-methyl-nicotinamide by about 80% at 2 h when dosed in mice orally at 50 mg/kg

756192

6-fluoro-1-methylquinolin-1-ium

6-methoxy-4-methylpyridine-3-carboxamide

756192

7-(3-carbamoylphenyl)hept-6-ynoic acid

inhibitor mimics the transition state of the methylation reaction

7-amino-1-methylquinolin-1-ium

9-(9-amino-5,6,7,8,9-pentadeoxy-6-ethynyl-beta-D-ribo-decofuranuronosyl)-9H-purin-6-amine

log Ki value 4.32

9-[9-amino-6-[(2-carbamoylphenyl)ethynyl]-5,6,7,8,9-pentadeoxy-beta-D-ribo-decofuranuronosyl]-9H-purin-6-amine

log Ki value 4.71

9-[9-amino-6-[(3-carbamoylphenyl)ethynyl]-5,6,7,8,9-pentadeoxy-beta-D-ribo-decofuranuronosyl]-9H-purin-6-amine

high-affinity, subnanomolar NNMT inhibitor

Cd2+

Clofibrate

Cu2+

Dimethylsulfoxide

competitive, about 82% inhibition at 1% v/v

N'-methyl-nicotinamide

N1-methylnicotinamide

Nickel

exposure of BEAS-2B cells to induces NNMT repression at both the protein and mRNA levels

nicotinamide

norharmane

S-adenosyl-L-homocysteine

4 entries

sinefungin

additional information

not inhibitory: Ca2+, SKF 525A, 3,4-dimethoxy-5-hydroxybenzoic acid

1-methyl nicotinamide

Macaca mulatta

F7ERX8

feedback inhibitor

755958

1-methyl nicotinamide

feedback inhibitor

1-methylnicotinamide

product inhibition

1-methylnicotinamide

product inhibition

5'-[[(3S)-3-amino-3-carboxypropyl][(3-carbamoylphenyl)methyl]amino]-5'-deoxyadenosine

bisubstrate inhibitor, competitive with respect to S-adenosyl-L-methionine, noncompetitive with respect to nicotinamide

5'-[[(3S)-3-amino-3-carboxypropyl][(3-carbamoylphenyl)methyl]amino]-5'-deoxyadenosine

inhibitor mimics the transition state of the methylation reaction

Clofibrate

inhibits the enzyme in liver micorosomes

Clofibrate

Rattus norvegicus

inhibits the enzyme in liver microsomes

N1-methylnicotinamide

N1-methylnicotinamide

IC50 0.06 mM for human protein, 0.03 mM for recombinant protein

nicotinamide

the enzyme shows substrate inhibition kinetics

nicotinamide

the enzyme shows substrate inhibition kinetics

nicotinamide

the enzyme shows substrate inhibition kinetics

S-adenosyl-L-homocysteine

S-adenosyl-L-homocysteine

product inhibition

S-adenosyl-L-homocysteine

757899, 758793

S-adenosyl-L-homocysteine

sinefungin

757406, 757899, 758793

sinefungin

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ACTIVATING COMPOUND

ORGANISM

UNIPROT

COMMENTARY

LITERATURE

IMAGE

imipramine

slightly but significantly activates the mouse liver NNMT enzyme and also changes the kinetic parameters Vmax, Km and Ki

Phenobarbital

additional information

Phenobarbital

activates 3-4fold in liver micorosomes

Phenobarbital

Rattus norvegicus

activates the enzyme in liver microsomes

additional information

elevated enzyme activity during cell differentiation in adipose tissue

701990

additional information

no activation by beta-naphthoflavone and ciprofibrate

Show Disease (181 entries)

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KM VALUE [mM]

SUBSTRATE

ORGANISM

UNIPROT

COMMENTARY

LITERATURE

IMAGE

0.2

1,2,3,4-tetrahydroisoquinoline

0.548

2-methoxypyridine

pH 8.6, 37°C

2.029

2-methylpyridine

pH 8.6, 37°C

0.727

3-acetylpyridine

pH 8.6, 37°C

0.335

4-methylnicotinamide

pH 8.6, 37°C

0.125

4-phenylpyridine

pH not specified in the publication, temperature not specified in the publication

0.087 - 1.5

Isoquinoline

0.003 - 11.8

nicotinamide

15 entries

1.326

nicotinimidamide

pH 8.6, 37°C

0.09

norharman

pH 8.6, 37°C

756000

0.01 - 1.3

Quinoline

0.364

quinoline 3-carboxamide

pH 8.6, 37°C

0.00176 - 3.5

S-adenosyl-L-methionine

13 entries

0.613

tetrahydroisoquinoline

pH 8.6, 37°C

0.111

Thionicotinamide

pH 8.6, 37°C

additional information

0.087

Isoquinoline

pH 8.6, 37°C

1.5

Isoquinoline

0.003

nicotinamide

pH 8.6, 37°C

0.02

nicotinamide

pH 7.5, temperature not specified in the publication

0.105

nicotinamide

K100A/E101A/E103A mutant protein, pH 8.6, 37°C

0.199

nicotinamide

pH 8.6, 37°C

0.24

nicotinamide

Y20F mutant protein, pH 8.6, 37°C

0.347

nicotinamide

0.37

nicotinamide

441258

0.38

nicotinamide

recombinant protein

0.4

nicotinamide

0.43-0.38 mM, wild type protein, pH 8.6, 37°C

0.43

nicotinamide

0.63

nicotinamide

Y20A mutant protein, pH 8.6, 37°C

0.83

nicotinamide

1.02

nicotinamide

pH 7.2, 37°C, liver homogenate

1.36

nicotinamide

pH 7.2, 37°C, liver homogenate

11.8

nicotinamide

D197A mutant protein, pH 8.6, 37°C

0.01

Quinoline

pH 8.6, 37°C

0.609

Quinoline

pH 8.6, 37°C

1.3

Quinoline

0.00176

S-adenosyl-L-methionine

0.0018

S-adenosyl-L-methionine

0.002

S-adenosyl-L-methionine

0.0018-0.0022 mM, wild type protein, pH 8.6, 37°C

0.0022

S-adenosyl-L-methionine

recombinant protein

0.005

S-adenosyl-L-methionine

K100A/E101A/E103A mutant protein, pH 8.6, 37°C

0.0065

S-adenosyl-L-methionine

441258

0.0085

S-adenosyl-L-methionine

pH 8.6, 37°C

0.01

S-adenosyl-L-methionine

pH 8.6, 37°C

0.016

S-adenosyl-L-methionine

0.024

S-adenosyl-L-methionine

pH 7.5, temperature not specified in the publication

0.028

S-adenosyl-L-methionine

Y20F mutant protein, pH 8.6, 37°C

2.73

S-adenosyl-L-methionine

D197A mutant protein, pH 8.6, 37°C

3.5

S-adenosyl-L-methionine

Y20A mutant protein, pH 8.6, 37°C

additional information

Michaelis-Menten kinetics

additional information

Michaelis-Menten kinetics

additional information

Michaelis-Menten kinetics, the Km value cannot be determined using Michaelis-Menten kinetic modelling

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TURNOVER NUMBER [1/s]

SUBSTRATE

ORGANISM

UNIPROT

COMMENTARY

LITERATURE

IMAGE

0.002

2-methoxypyridine

pH 8.6, 37°C

0.01

2-methylpyridine

pH 8.6, 37°C

0.014

3-acetylpyridine

pH 8.6, 37°C

0.091

4-methylnicotinamide

pH 8.6, 37°C

0.000093

4-phenylpyridine

pH not specified in the publication, temperature not specified in the publication

0.017

Isoquinoline

pH 8.6, 37°C

0.014 - 1.02

nicotinamide

8 entries

0.014

nicotinimidamide

pH 8.6, 37°C

0.0004

norharman

pH 8.6, 37°C

756000

0.011 - 0.046

Quinoline

0.007

quinoline 3-carboxamide

pH 8.6, 37°C

0.008 - 0.068

S-adenosyl-L-methionine

0.045

tetrahydroisoquinoline

pH 8.6, 37°C

0.033

Thionicotinamide

pH 8.6, 37°C

0.014

nicotinamide

pH 8.6, 37°C

0.031

nicotinamide

Y20A mutant protein, pH 8.6, 37°C

0.036

nicotinamide

D197A mutant protein, pH 8.6, 37°C

0.041

nicotinamide

Y20F mutant protein, pH 8.6, 37°C

0.077

nicotinamide

0.43-0.38 mM, wild type protein, pH 8.6, 37°C

0.083

nicotinamide

K100A/E101A/E103A mutant protein, pH 8.6, 37°C

0.102

nicotinamide

pH 8.6, 37°C

1.02

nicotinamide

pH 7.2, 37°C, liver homogenate

0.011

Quinoline

pH 8.6, 37°C

0.046

Quinoline

pH 8.6, 37°C

0.008

S-adenosyl-L-methionine

pH 8.6, 37°C

0.068

S-adenosyl-L-methionine

pH 7.5, temperature not specified in the publication

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kcat/KM VALUE [1/mMs^-1]

SUBSTRATE

ORGANISM

UNIPROT

COMMENTARY

LITERATURE

IMAGE

0.005

2-methoxypyridine

pH 8.6, 37°C

0.005

2-methylpyridine

pH 8.6, 37°C

0.02

3-acetylpyridine

pH 8.6, 37°C

0 - 273

4-methylnicotinamide

pH 8.6, 37°C

0.0008

4-phenylpyridine

pH not specified in the publication, temperature not specified in the publication

0.197

Isoquinoline

pH 8.6, 37°C

0.003 - 4.7

nicotinamide

7 entries

0.01

nicotinimidamide

pH 8.6, 37°C

0.003

norharman

pH 8.6, 37°C

756000

0.076 - 1.1

Quinoline

0.02

quinoline 3-carboxamide

pH 8.6, 37°C

0.009 - 39

S-adenosyl-L-methionine

6 entries

0.074

tetrahydroisoquinoline

pH 8.6, 37°C

0.3

Thionicotinamide

pH 8.6, 37°C

0.003

nicotinamide

D197A mutant protein, pH 8.6, 37°C

0.005

nicotinamide

Y20A mutant protein, pH 8.6, 37°C

0.17

nicotinamide

Y20F mutant protein, pH 8.6, 37°C

0.19

nicotinamide

0.18-0.2 1/sec*mM, wild type protein, pH 8.6, 37°C

0.51

nicotinamide

pH 8.6, 37°C

0.8

nicotinamide

K100A/E101A/E103A mutant protein, pH 8.6, 37°C

4.7

nicotinamide

pH 8.6, 37°C

0.076

Quinoline

pH 8.6, 37°C

1.1

Quinoline

pH 8.6, 37°C

0.009

S-adenosyl-L-methionine

Y20A mutant protein, pH 8.6, 37°C

0.013

S-adenosyl-L-methionine

D197A mutant protein, pH 8.6, 37°C

0.75

S-adenosyl-L-methionine

pH 8.6, 37°C

1.5

S-adenosyl-L-methionine

Y20F mutant protein, pH 8.6, 37°C

S-adenosyl-L-methionine

K100A/E101A/E103A mutant protein, pH 8.6, 37°C

S-adenosyl-L-methionine

35-43 1/sec*mM, wild type protein, pH 8.6, 37°C

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Ki VALUE [mM]

INHIBITOR

ORGANISM

UNIPROT

COMMENTARY

LITERATURE

IMAGE

0.0000005

9-[9-amino-6-[(3-carbamoylphenyl)ethynyl]-5,6,7,8,9-pentadeoxy-beta-D-ribo-decofuranuronosyl]-9H-purin-6-amine

pH not specified in the publication, temperature not specified in the publication

4 - 34

Dimethylsulfoxide

3.57 - 50.64

nicotinamide

Dimethylsulfoxide

substrate concentration above 2.5 mM, pH not specified in the publication, temperature not specified in the publication

Dimethylsulfoxide

substrate concentration below 2.5 mM, pH not specified in the publication, temperature not specified in the publication

3.57

nicotinamide

pH 7.2, 37°C, liver homogenate

20.01

nicotinamide

pH 7.2, 37°C, liver homogenate