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Information on EC 2.1.1.28 - phenylethanolamine N-methyltransferase
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EC Tree
2.1.1.28 phenylethanolamine N-methyltransferaseIUBMB Comments
Acts on various phenylethanolamines; converts noradrenaline into adrenaline.
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Word Map
- 2.1.1.28
- catecholamine
- medulla
- hydroxylase
-
adrenergic
- dopamine
-
chromaffin
- beta-hydroxylase
- glucocorticoid
-
sympathetic
-
rostrally
-
catecholaminergic
-
noradrenergic
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innervation
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ventrolateral
- hypothalamic
- corticosterone
-
catecholamine-synthesizing
- oblongata
- dopamine-beta-hydroxylase
-
pnmt-immunoreactive
- perikarya
-
tractus
-
adrenomedullary
- proenkephalin
-
dorsomedial
-
sympathoadrenal
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intermediolateral
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alpha2-adrenoceptor
- 1,2,3,4-tetrahydroisoquinoline
-
coeruleus
-
phenylethanolamine-n-methyltransferase
-
postrema
-
pnmt-ir
- medicine
-
bulbospinal
- normetanephrine
-
solitarii
- analysis
The enzyme appears in viruses and cellular organisms
Reaction Schemes
Synonyms
phenylethanolamine n-methyltransferase, hpnmt, norepinephrine n-methyltransferase, noradrenaline n-methyltransferase, s-adenosyl-l-methionine:phenylethanolamine n-methyltransferase, noradrenalin n-methyltransferase, phenethanolamine n-methyltransferase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
methyltransferase, noradrenaline N-
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NMT
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-
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noradrenalin methyltransferase
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-
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noradrenalin N-methyltransferase
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noradrenaline N-methyltransferase
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-
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norepinephrin N-methyltransferase
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norepinephrine methyltransferase
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-
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norepinephrine N-methyltransferase
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phenethanolamine methyltransferase
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phenethanolamine N-methyltransferase
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PNMT
PNMT
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-
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PNMT
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + phenylethanolamine = S-adenosyl-L-homocysteine + N-methylphenylethanolamine
S-adenosyl-L-methionine + phenylethanolamine = S-adenosyl-L-homocysteine + N-methylphenylethanolamine
random binding mechanism with a kinetically preferred order of binding where S-adenosyl-L-methionine is the preferred first substrate
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S-adenosyl-L-methionine + phenylethanolamine = S-adenosyl-L-homocysteine + N-methylphenylethanolamine
ordered sequential reaction
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S-adenosyl-L-methionine + phenylethanolamine = S-adenosyl-L-homocysteine + N-methylphenylethanolamine
to elucidate the detailed mechanism of enzymatic catalysis of PNMT, combined quantum-mechanical/molecular-mechanical (QM/MM) calculations are performed. The calculation results reveal that this catalysis contains three elementary steps: the deprotonation of protonated norepinphrine, the methyl transferring step and deprotonation of the methylated norepinphrine. The methyl transferring step is proved to be the rate-determining step undergoing a SN2 mechanism with an energy barrier of 16.4 kcal/mol
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S-adenosyl-L-methionine + phenylethanolamine = S-adenosyl-L-homocysteine + N-methylphenylethanolamine
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
methyl group transfer
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PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
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SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase
Acts on various phenylethanolamines; converts noradrenaline into adrenaline.
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CAS REGISTRY NUMBER
COMMENTARY
9037-68-7
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-hydroxyphenylethanolamine + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
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i.e. o-octopamine
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-
?
3,4-dichlorophenyl ethanolamine + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
-
-
-
-
?
3,4-dichlorophenylethanolamine + S-adenosyl-L-methionine
N-methyl-3,4-dichlorophenylethanolamine + S-adenosyl-L-homocysteine
3,4-dihydroxynorephedrine + S-adenosyl-L-methionine
3,4-dihydroxyephedrine + S-adenosyl-L-homocysteine
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18% of the activity with normetanephrine
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-
?
3-chloro-4-hydroxyphenylethanolamine + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
3-hydroxyphenylethanolamine + S-adenosyl-L-methionine
N-methyl-m-octopamine + S-adenosyl-L-homocysteine
3-trifluoromethylphenylethanolamine + S-adenosyl-L-methionine
N-methyl-3-trifluoromethylphenylethanolamine + S-adenosyl-L-homocysteine
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-
-
?
4-hydroxynorephedrine + S-adenosyl-L-methionine
4-hydroxyephedrine + S-adenosyl-L-homocysteine
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18% of the activity with normetanephrine
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-
?
4-hydroxyphenylethanolamine + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
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i.e. octopamine
-
-
?
anti-9-amino-6-(trifluoromethyl)benzonorbornene + S-adenosyl-L-methionine
?
-
-
-
?
cis-(1R,2S)-2-amino-1-tetralol + S-adenosyl-L-methionine
cis-(1R,2S)-2-methylamino-1-tetralol + S-adenosyl-L-homocysteine
-
-
-
?
DL-m-hydroxyphenylethanolamine + S-adenosyl-L-methionine
neosynephrine + S-adenosyl-L-homocysteine
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60% of the activity with normetanephrine
-
-
?
DL-neo-synephrine + S-adenosyl-L-methionine
3-hydroxy-alpha-[(dimethylamine)methyl]benzenemethanol + S-adenosyl-L-homocysteine
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20% of the activity with normetanephrine
-
-
?
DL-octopamine + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
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18% of the activity with normetanephrine
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-
?
L-norephedrine + S-adenosyl-L-methionine
ephedrine + S-adenosyl-L-homocysteine
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14% of the activity with normetanephrine
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-
?
phenylethanolamine + S-adenosyl-L-methionine
N-methylphenylethanolamine + S-adenosyl-L-homocysteine
S-adenosyl-L-methionine + 4-aminomethyl-1,2,3,4-tetrahydroisoquinoline
S-adenosyl-L-homocysteine + ?
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-
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?
S-adenosyl-L-methionine + noradrenaline
S-adenosyl-L-homocysteine + epinephrine
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-
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?
S-adenosyl-L-methionine + phenylethanolamine
S-adenosyl-L-homocysteine + N-methylphenylethanolamine
3,4-dichlorophenylethanolamine + S-adenosyl-L-methionine
N-methyl-3,4-dichlorophenylethanolamine + S-adenosyl-L-homocysteine
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-
-
-
?
3,4-dichlorophenylethanolamine + S-adenosyl-L-methionine
N-methyl-3,4-dichlorophenylethanolamine + S-adenosyl-L-homocysteine
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-
-
-
?
3,4-dichlorophenylethylenediamine + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
-
-
-
-
?
3,4-dichlorophenylethylenediamine + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
-
-
-
-
?
3-chloro-4-hydroxyphenylethanolamine + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
-
-
-
-
?
3-chloro-4-hydroxyphenylethanolamine + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
-
-
-
-
?
3-hydroxyphenylethanolamine + S-adenosyl-L-methionine
N-methyl-m-octopamine + S-adenosyl-L-homocysteine
-
-
-
?
3-hydroxyphenylethanolamine + S-adenosyl-L-methionine
N-methyl-m-octopamine + S-adenosyl-L-homocysteine
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i.e. m-octopamine
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-
?
9-methylnorharman + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
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2N-methylation
-
-
?
9-methylnorharman + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
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PNMT catalyzes the 2N-methylation of beta-carbolines, forming 2N-methylated beta-carbolinium cations, which are structural and functional analogs of the Parkinsonian-inducing toxin MPP+
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-
?
D-norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
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15% of the activity with normetanephrine
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-
?
D-norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
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-
-
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?
L-norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
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-
-
-
?
L-norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
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21% of the activity with normetanephrine
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-
?
L-norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
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-
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?
norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
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-
-
-
?
norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
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-
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?
norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
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-
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?
norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
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?
norepinephrine + S-adenosyl-L-methionine
epinephrine + S-adenosyl-L-homocysteine
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?
normetanephrine + S-adenosyl-L-methionine
metanephrine + S-adenosyl-L-homocysteine
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?
normetanephrine + S-adenosyl-L-methionine
metanephrine + S-adenosyl-L-homocysteine
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?
normetanephrine + S-adenosyl-L-methionine
metanephrine + S-adenosyl-L-homocysteine
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i.e. 3-methoxy-4-hydroxyphenylethanolamine
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-
?
octopamine + S-adenosyl-L-methionine
N-methyloctopamine + S-adenosyl-L-homocysteine
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-
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?
octopamine + S-adenosyl-L-methionine
N-methyloctopamine + S-adenosyl-L-homocysteine
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-
-
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?
phenylethanolamine + S-adenosyl-L-methionine
N-methylphenylethanolamine + S-adenosyl-L-homocysteine
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?
phenylethanolamine + S-adenosyl-L-methionine
N-methylphenylethanolamine + S-adenosyl-L-homocysteine
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-
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?
phenylethanolamine + S-adenosyl-L-methionine
N-methylphenylethanolamine + S-adenosyl-L-homocysteine
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-
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?
phenylethanolamine + S-adenosyl-L-methionine
N-methylphenylethanolamine + S-adenosyl-L-homocysteine
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72% of the activity with normetanephrine
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?
phenylethanolamine + S-adenosyl-L-methionine
N-methylphenylethanolamine + S-adenosyl-L-homocysteine
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?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
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?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
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last step in biosynthesis of epinephrine
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?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
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terminal step in epinephrine biosynthesis
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?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
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-
-
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?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
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epinephrine is an important neurotransmitter and hormone, and epinephrine is required for normal blood pressure and cardiac filling responses to stress, but is not required for tachycardia during stress or normal cardiovascular function at rest
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-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
-
-
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
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epinephrine is an important neurotransmitter and hormone, and epinephrine is required for normal blood pressure and cardiac filling responses to stress, but is not required for tachycardia during stress or normal cardiovascular function at rest
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
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?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
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last step in biosynthesis of epinephrine
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?
S-adenosyl-L-methionine + phenylethanolamine
S-adenosyl-L-homocysteine + N-methylphenylethanolamine
-
-
-
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?
S-adenosyl-L-methionine + phenylethanolamine
S-adenosyl-L-homocysteine + N-methylphenylethanolamine
-
-
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?
S-adenosyl-L-methionine + phenylethanolamine
S-adenosyl-L-homocysteine + N-methylphenylethanolamine
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?
additional information
?
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enzyme is involved in biosynthesis of epinephrine
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?
additional information
?
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the enzyme is involved in norepinephrine pathways
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?
additional information
?
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enzyme does not react with benzylisoquinolines: tetrahydropapaveroline (THP), 6-O-methyl-THP, 4'-O-methyl-THP and norreticuline
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-
?
additional information
?
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enzyme operates by an ordered sequential mechanism in which AdoMet binds first. A protonated and an unprotonated group are required for catalysis
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-
?
additional information
?
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enzyme operates by an ordered sequential mechanism in which AdoMet binds first. A protonated and an unprotonated group are required for catalysis
-
-
?
additional information
?
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the phenylethanolamine N-methyltransferase GRE plays a necessary, but not sufficient role in the transcriptional aspects to the control mechanism. Analyses implicate the participation of sequences in the distal 5´promoter of this gene.
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-
?
additional information
?
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terminal enzyme in the biosynthetic pathway for epinephrine
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?
additional information
?
-
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final enzyme in the pathway for epinephrine biosynthesis
-
-
?
additional information
?
-
-
the enzyme binds to the alpha-adrenoreceptor
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
9-methylnorharman + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
-
PNMT catalyzes the 2N-methylation of beta-carbolines, forming 2N-methylated beta-carbolinium cations, which are structural and functional analogs of the Parkinsonian-inducing toxin MPP+
-
-
?
S-adenosyl-L-methionine + phenylethanolamine
S-adenosyl-L-homocysteine + N-methylphenylethanolamine
-
-
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
-
last step in biosynthesis of epinephrine
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
-
terminal step in epinephrine biosynthesis
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
-
epinephrine is an important neurotransmitter and hormone, and epinephrine is required for normal blood pressure and cardiac filling responses to stress, but is not required for tachycardia during stress or normal cardiovascular function at rest
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
-
epinephrine is an important neurotransmitter and hormone, and epinephrine is required for normal blood pressure and cardiac filling responses to stress, but is not required for tachycardia during stress or normal cardiovascular function at rest
-
-
?
S-adenosyl-L-methionine + norepinephrine
S-adenosyl-L-homocysteine + epinephrine
-
last step in biosynthesis of epinephrine
-
-
?
additional information
?
-
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enzyme is involved in biosynthesis of epinephrine
-
-
?
additional information
?
-
-
the enzyme is involved in norepinephrine pathways
-
-
?
additional information
?
-
-
the phenylethanolamine N-methyltransferase GRE plays a necessary, but not sufficient role in the transcriptional aspects to the control mechanism. Analyses implicate the participation of sequences in the distal 5´promoter of this gene.
-
-
?
additional information
?
-
-
terminal enzyme in the biosynthetic pathway for epinephrine
-
-
?
additional information
?
-
-
final enzyme in the pathway for epinephrine biosynthesis
-
-
?
additional information
?
-
-
the enzyme binds to the alpha-adrenoreceptor
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
very high selectivity
3-(fluoromethyl)-7-(thiomorpholin-4-ylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
-
3-(fluoromethyl)-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
very high selectivity
3-(fluoromethyl)-N-(3,3,3-trifluoropropyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
-
3-difluoromethyl-7-(N-2,2,2-trifluoroethylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
-
3-difluoromethyl-7-(N-3-methoxypropylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
-
3-difluoromethyl-7-(N-4-nitrophenylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
-
3-ethyl-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
moderate selectivity
3-fluoromethyl-7-(2,2,2-trifluoroethylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
3-fluoromethyl-7-(3,3,3-trifluoropropylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
3-fluoromethyl-7-(4,4,4-trifluorobutylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
3-fluoromethyl-7-(4-chlorobenzylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
-
3-fluoromethyl-7-[N-(4-chlorophenyl)aminosulfonyl]-1,2,3,4-tetrahydroisoquinoline
-
-
3-hydroxypropyl-7-bromo-1,2,3,4-tetrahydroisoquinoline
-
extension of the 3-hydroxyalkyl chain by just one carbon results in a significant loss in phenylethanolamine N-methyltransferse inhibitory potency
3-methyl-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
high selectivity
3-propyl-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide
-
moderate selectivity
3-thienylmethylamine
-
inhibits the enzyme and is selective toward the alpha2-adrenoceptor
3-trifluoromethyl-1,2,3,4-tetrahydroisoquinolines
-
several 3-trifluoromethyl-1,2,3,4-tetrahydroisoquinolines and some enantiomers of 3-trifuoromethyl-1,2,3,4-tetrahydroisoquinolines. For the phenylethanolamine N-methyltransferase inhibitory potency of different 3-trifuoromethyl-1,2,3,4-tetrahydroisoquinolines, compounds bearing a lipophilic 7-substituent show higher potency than compounds bearing a hydrophilic 7-substituent. Comparison to the inhibitory activity of the entantiomers of the most potent racemates show that the R-enantiomers are approximately 4fold as potent as their corresponding S-enantiomers.
-
5,6-Dichloro-2-aminotetralin
-
0.00093 mM, 50% inhibition, competitive with norepinephrine as substrate
7-(3-methoxypropylsulfonyl)-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
7-(N-4-chlorophenylaminosulfonyl)-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline
-
-
7-bromo-1,2,3,4-tetrahydrobenzo[h]isoquinoline
-
7-bromo-1,2,3,4-tetrahydroben[h]isoquinoline is 2fold more potent as an inhibitor of phenylethanolamine N-methyltransferase than 1,2,3,4-tetrahydroben[h]isoquinoline.