PARTICIPANT STOICHIOMETRY re20 132
type: Stoichiometry
physical entity: NADPH
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re20 133
type: Stoichiometry
physical entity: cotinine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re20 134
type: Stoichiometry
physical entity: NADP+
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re20 135
type: Stoichiometry
physical entity: 5'-hydroxycotinine
stoichiometric coefficient: 1.0

UNKNOWN_TRANSITION
type: RelationshipTypeVocabulary

formaldehyde
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

PARTICIPANT STOICHIOMETRY re20 131
type: Stoichiometry
physical entity: O2
stoichiometric coefficient: 1.0

trans-3'-hydroxycotinine N-glucuronide
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

PARTICIPANT STOICHIOMETRY re22 127
type: Stoichiometry
physical entity: cotinine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re22 128
type: Stoichiometry
physical entity: cotinine N-oxide
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re34 35
type: Stoichiometry
physical entity: trans-3'-hydroxycotinine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re34 36
type: Stoichiometry
physical entity: trans-3'-hydroxycotinine N-glucuronide
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re29 104
type: Stoichiometry
physical entity: 4-(3-pyridyl)-3-butanoate
stoichiometric coefficient: 1.0

CATALYSIS
type: Catalysis
controlled: STATE_TRANSITION_LEFT__O2-_NADPH-_cotinine-RIGHT__NADP_PLUS_-_H2O-_N_hydroxymethyl_norcotinine-_re25
controller: CYP2A6

STATE_TRANSITION_LEFT__NADPH-_nicotine-RIGHT__NADP_PLUS_-_nicotine__DELTA_1_5_iminium_ion-_re1
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re1 90
participant stoichiometry: PARTICIPANT STOICHIOMETRY re1 89
participant stoichiometry: PARTICIPANT STOICHIOMETRY re1 91
participant stoichiometry: PARTICIPANT STOICHIOMETRY re1 88
left: NADPH
left: nicotine
interaction type: STATE_TRANSITION
right: nicotine-_DELTA_1 5-iminium ion
right: NADP+

STATE_TRANSITION_LEFT__nicotine-_UDP_D_glucuronate-RIGHT__UDP-_nicotine_glucuronide-_re6
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re6 57
participant stoichiometry: PARTICIPANT STOICHIOMETRY re6 60
participant stoichiometry: PARTICIPANT STOICHIOMETRY re6 58
participant stoichiometry: PARTICIPANT STOICHIOMETRY re6 59
left: UDP-D-glucuronate
left: nicotine
interaction type: STATE_TRANSITION
right: nicotine-glucuronide
right: UDP

PARTICIPANT STOICHIOMETRY re29 103
type: Stoichiometry
physical entity: 4-hydroxy-4-(3-pyridyl)-butanoate
stoichiometric coefficient: 1.0

UNKNOWN_TRANSITION_LEFT__4_oxo_4__3_pyridyl__N_methylbutanamide-RIGHT__4_oxo_4__3_pyridyl__butanoate-_re27
type: Conversion
conversion direction: LEFT_TO_RIGHT
xref: UNKNOWN TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re27 108
participant stoichiometry: PARTICIPANT STOICHIOMETRY re27 107
left: 4-oxo-4-(3-pyridyl)-N-methylbutanamide
interaction type: UNKNOWN_TRANSITION
right: 4-oxo-4-(3-pyridyl)-butanoate

trans-3'-hydroxycotinine
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

By Homology
type: RelationshipTypeVocabulary

trans-3'-hydroxycotinine O-glucuronide
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

Dimethylaniline monooxygenase [N-oxide-forming]
type: ProteinReference
xref: uniprot F7HQX7 2
xref: PTHR23023:SF44
organism: Macaca mulatta

uniprot F7GYG0 27
type: UnificationXref
id: F7GYG0
db: uniprot

uniprot Q16696 30
type: UnificationXref
id: Q16696
db: uniprot

UNKNOWN_TRANSITION_LEFT__4__3_pyridyl__butanoate-RIGHT__3_pyridylacetate-_re31
type: Conversion
conversion direction: LEFT_TO_RIGHT
xref: UNKNOWN TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re31 41
participant stoichiometry: PARTICIPANT STOICHIOMETRY re31 42
left: 4-(3-pyridyl)-butanoate
interaction type: UNKNOWN_TRANSITION
right: 3-pyridylacetate

uniprot A0A1D5R3N7 26
type: UnificationXref
id: A0A1D5R3N7
db: uniprot

STATE_TRANSITION_LEFT__nicotine-_S_adenosyl_L_methionine-RIGHT__S_adenosyl_homocysteine-_nicotine_isomethonium_ion-_re4
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re4 75
participant stoichiometry: PARTICIPANT STOICHIOMETRY re4 73
participant stoichiometry: PARTICIPANT STOICHIOMETRY re4 74
participant stoichiometry: PARTICIPANT STOICHIOMETRY re4 76
left: nicotine
left: S-adenosyl-L-methionine
interaction type: STATE_TRANSITION
right: S-adenosyl-homocysteine
right: nicotine isomethonium ion

PARTICIPANT STOICHIOMETRY re14 92
type: Stoichiometry
physical entity: 4-oxo-4-(3-pyridyl)-butanoate
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re14 93
type: Stoichiometry
physical entity: 4-hydroxy-4-(3-pyridyl)-butanoate
stoichiometric coefficient: 1.0

UNKNOWN_TRANSITION_LEFT__H2O-_nicotine-RIGHT__formaldehyde-_nornicotine-_re9
type: Conversion
conversion direction: LEFT_TO_RIGHT
xref: UNKNOWN TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re9 48
participant stoichiometry: PARTICIPANT STOICHIOMETRY re9 45
participant stoichiometry: PARTICIPANT STOICHIOMETRY re9 47
participant stoichiometry: PARTICIPANT STOICHIOMETRY re9 46
left: H2O
left: nicotine
interaction type: UNKNOWN_TRANSITION
right: nornicotine
right: formaldehyde

CATALYSIS
type: Catalysis
controlled: STATE_TRANSITION_LEFT__O2-_NADPH-_nicotine-RIGHT__NADP_PLUS_-_H2O-_nicotine_1_N_oxide-_re5
controller: FMO3

PARTICIPANT STOICHIOMETRY re12 96
type: Stoichiometry
physical entity: 4-oxo-4-(3-pyridyl)-butanamide
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re12 97
type: Stoichiometry
physical entity: 4-oxo-4-(3-pyridyl)-butanoate
stoichiometric coefficient: 1.0

P05979
type: UnificationXref
id: P05979
db: PANTHER Pathway Component

UNKNOWN_TRANSITION_LEFT__4_hydroxy_4__3_pyridyl__butanoate-RIGHT__4__3_pyridyl__3_butanoate-_re15
type: Conversion
conversion direction: LEFT_TO_RIGHT
xref: UNKNOWN TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re15 87
participant stoichiometry: PARTICIPANT STOICHIOMETRY re15 86
left: 4-hydroxy-4-(3-pyridyl)-butanoate
interaction type: UNKNOWN_TRANSITION
right: 4-(3-pyridyl)-3-butanoate

4-oxo-4-(3-pyridyl)-butanoate
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

CATALYSIS
type: Catalysis
controlled: STATE_TRANSITION_LEFT__O2-_NADPH-_cotinine-RIGHT__NADP_PLUS_-_trans_3_QUOTE_SINGLE_hydroxycotinine-_H2O-_re19
controller: CYP2A6

CATALYSIS
type: Catalysis
controlled: STATE_TRANSITION_LEFT__cotinine-_UDP_D_glucuronate-RIGHT__UDP-_cotinine_glucuronide-_re24
controller: UGT1A4

P05980
type: UnificationXref
id: P05980
db: PANTHER Pathway Component

P05981
type: UnificationXref
id: P05981
db: PANTHER Pathway Component

P05982
type: UnificationXref
id: P05982
db: PANTHER Pathway Component

UDP-D-glucuronate
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

Mus musculus
type: BioSource
xref: ncbitaxon 10090 10

P05984
type: UnificationXref
id: P05984
db: PANTHER Pathway Component

STATE_TRANSITION_LEFT__cotinine-RIGHT__cotinine_methonium_ion-_re23
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re23 126
participant stoichiometry: PARTICIPANT STOICHIOMETRY re23 125
left: cotinine
interaction type: STATE_TRANSITION
right: cotinine methonium ion

uniprot F7GW14 22
type: UnificationXref
id: F7GW14
db: uniprot

ncbitaxon 9615 14
type: UnificationXref
id: 9615
db: ncbitaxon

PARTICIPANT STOICHIOMETRY re20 136
type: Stoichiometry
physical entity: H2O
stoichiometric coefficient: 1.0

UNKNOWN_TRANSITION_LEFT__4_hydroxy_4__3_pyridyl__butanoate-RIGHT__4__3_pyridyl__3_butanoate-_re29
type: Conversion
conversion direction: LEFT_TO_RIGHT
xref: UNKNOWN TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re29 104
participant stoichiometry: PARTICIPANT STOICHIOMETRY re29 103
left: 4-hydroxy-4-(3-pyridyl)-butanoate
interaction type: UNKNOWN_TRANSITION
right: 4-(3-pyridyl)-3-butanoate

uniprot P16662 17
type: UnificationXref
id: P16662
db: uniprot

PARTICIPANT STOICHIOMETRY re15 87
type: Stoichiometry
physical entity: 4-(3-pyridyl)-3-butanoate
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re15 86
type: Stoichiometry
physical entity: 4-hydroxy-4-(3-pyridyl)-butanoate
stoichiometric coefficient: 1.0

uniprot P35503 24
type: UnificationXref
id: P35503
db: uniprot

ISS
type: EvidenceCodeVocabulary
xref: eco ECO:0000250 4

PARTICIPANT STOICHIOMETRY re7 56
type: Stoichiometry
physical entity: O2
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re7 55
type: Stoichiometry
physical entity: 2-hydroxynicotine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re7 54
type: Stoichiometry
physical entity: NADP+
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re7 53
type: Stoichiometry
physical entity: nicotine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re7 52
type: Stoichiometry
physical entity: H2O
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re7 51
type: Stoichiometry
physical entity: NADPH
stoichiometric coefficient: 1.0

UNKNOWN_TRANSITION_LEFT__4__3_pyridyl__3_butanoate-RIGHT__4__3_pyridyl__butanoate-_re16
type: Conversion
conversion direction: LEFT_TO_RIGHT
xref: UNKNOWN TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re16 80
participant stoichiometry: PARTICIPANT STOICHIOMETRY re16 79
left: 4-(3-pyridyl)-3-butanoate
interaction type: UNKNOWN_TRANSITION
right: 4-(3-pyridyl)-butanoate

PARTICIPANT STOICHIOMETRY re16 80
type: Stoichiometry
physical entity: 4-(3-pyridyl)-butanoate
stoichiometric coefficient: 1.0

Dimethylaniline monooxygenase [N-oxide-forming] 3
type: ProteinReference
xref: uniprot P97501 9
organism: Mus musculus

O2
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

STATE_TRANSITION_LEFT__NADPH-_H2O-_nicotine-RIGHT__NADP_PLUS_-_2_hydroxynicotine-_O2-_re7
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re7 56
participant stoichiometry: PARTICIPANT STOICHIOMETRY re7 52
participant stoichiometry: PARTICIPANT STOICHIOMETRY re7 54
participant stoichiometry: PARTICIPANT STOICHIOMETRY re7 55
participant stoichiometry: PARTICIPANT STOICHIOMETRY re7 53
participant stoichiometry: PARTICIPANT STOICHIOMETRY re7 51
left: H2O
left: NADPH
left: nicotine
interaction type: STATE_TRANSITION
right: O2
right: 2-hydroxynicotine
right: NADP+

PARTICIPANT STOICHIOMETRY re13 95
type: Stoichiometry
physical entity: 4-oxo-4-(3-pyridyl)-butanoate
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re13 94
type: Stoichiometry
physical entity: 4-(methylamino)-1-(3-pyridyl)-1-butanone
stoichiometric coefficient: 1.0

UNKNOWN_TRANSITION_LEFT__4__3_pyridyl__butanoate-RIGHT__3_pyridylacetate-_re17
type: Conversion
conversion direction: LEFT_TO_RIGHT
xref: UNKNOWN TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re17 77
participant stoichiometry: PARTICIPANT STOICHIOMETRY re17 78
left: 4-(3-pyridyl)-butanoate
interaction type: UNKNOWN_TRANSITION
right: 3-pyridylacetate

PARTICIPANT STOICHIOMETRY re24 123
type: Stoichiometry
physical entity: UDP
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re24 124
type: Stoichiometry
physical entity: cotinine-glucuronide
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re24 121
type: Stoichiometry
physical entity: cotinine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re24 122
type: Stoichiometry
physical entity: UDP-D-glucuronate
stoichiometric coefficient: 1.0

H2O
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

PARTICIPANT STOICHIOMETRY re16 79
type: Stoichiometry
physical entity: 4-(3-pyridyl)-3-butanoate
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re17 77
type: Stoichiometry
physical entity: 4-(3-pyridyl)-butanoate
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re17 78
type: Stoichiometry
physical entity: 3-pyridylacetate
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re33 37
type: Stoichiometry
physical entity: 4-oxo-4-(3-pyridyl)-butanamide
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re33 38
type: Stoichiometry
physical entity: 4-oxo-4-(3-pyridyl)-butanoate
stoichiometric coefficient: 1.0

UDP-glucuronosyltransferase 1-3
type: ProteinReference
xref: PTHR48050:SF12
xref: uniprot P35503 24
organism: Homo sapiens

STATE_TRANSITION_LEFT__cotinine-_UDP_D_glucuronate-RIGHT__UDP-_cotinine_glucuronide-_re24
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re24 123
participant stoichiometry: PARTICIPANT STOICHIOMETRY re24 121
participant stoichiometry: PARTICIPANT STOICHIOMETRY re24 122
participant stoichiometry: PARTICIPANT STOICHIOMETRY re24 124
left: cotinine
left: UDP-D-glucuronate
interaction type: STATE_TRANSITION
right: cotinine-glucuronide
right: UDP

STATE_TRANSITION_LEFT__O2-_H2O-_nicotine__DELTA_1_5_iminium_ion-RIGHT__H2O2-_cotinine-_re2
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re2 81
participant stoichiometry: PARTICIPANT STOICHIOMETRY re2 85
participant stoichiometry: PARTICIPANT STOICHIOMETRY re2 83
participant stoichiometry: PARTICIPANT STOICHIOMETRY re2 84
participant stoichiometry: PARTICIPANT STOICHIOMETRY re2 82
left: H2O
left: nicotine-_DELTA_1 5-iminium ion
left: O2
interaction type: STATE_TRANSITION
right: cotinine
right: H2O2

UNKNOWN_TRANSITION_LEFT__4_oxo_4__3_pyridyl__butanoate-RIGHT__4_hydroxy_4__3_pyridyl__butanoate-_re14
type: Conversion
conversion direction: LEFT_TO_RIGHT
xref: UNKNOWN TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re14 93
participant stoichiometry: PARTICIPANT STOICHIOMETRY re14 92
left: 4-oxo-4-(3-pyridyl)-butanoate
interaction type: UNKNOWN_TRANSITION
right: 4-hydroxy-4-(3-pyridyl)-butanoate

Pan troglodytes
type: BioSource
xref: ncbitaxon 9598 12

H2O2
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

UDP-glucuronosyltransferase 2B7
type: ProteinReference
xref: uniprot P16662 17
xref: PTHR48043:SF87
organism: Homo sapiens

nicotine isomethonium ion
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

UNKNOWN_TRANSITION_LEFT__4__3_pyridyl__3_butanoate-RIGHT__4__3_pyridyl__butanoate-_re30
type: Conversion
conversion direction: LEFT_TO_RIGHT
xref: UNKNOWN TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re30 44
participant stoichiometry: PARTICIPANT STOICHIOMETRY re30 43
left: 4-(3-pyridyl)-3-butanoate
interaction type: UNKNOWN_TRANSITION
right: 4-(3-pyridyl)-butanoate

uniprot P31513 6
type: UnificationXref
id: P31513
db: uniprot

CATALYSIS
type: Catalysis
controlled: STATE_TRANSITION_LEFT__O2-_NADPH-_cotinine-RIGHT__NADP_PLUS_-_5_QUOTE_SINGLE_hydroxycotinine-_H2O-_re20
controller: CYP2A6

PTHR48043:SF87
type: RelationshipXref
id: PTHR48043:SF87
db: PANTHER Family
relationship type: By Homology

UDP
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

Uncharacterized protein
type: ProteinReference
xref: uniprot A0A1D5R3N7 26
organism: Macaca mulatta

UDP-glucuronosyltransferase 1-5
type: ProteinReference
xref: uniprot P35504 25
xref: PTHR48050:SF12
organism: Homo sapiens

STATE_TRANSITION_LEFT__cotinine-RIGHT__cotinine_N_oxide-_re22
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re22 128
participant stoichiometry: PARTICIPANT STOICHIOMETRY re22 127
left: cotinine
interaction type: STATE_TRANSITION
right: cotinine N-oxide

UNKNOWN_TRANSITION_LEFT__4_oxo_4__3_pyridyl__butanoate-RIGHT__4_hydroxy_4__3_pyridyl__butanoate-_re28
type: Conversion
conversion direction: LEFT_TO_RIGHT
xref: UNKNOWN TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re28 106
participant stoichiometry: PARTICIPANT STOICHIOMETRY re28 105
left: 4-oxo-4-(3-pyridyl)-butanoate
interaction type: UNKNOWN_TRANSITION
right: 4-hydroxy-4-(3-pyridyl)-butanoate

Cytochrome P450 2A7
type: ProteinReference
xref: uniprot P20853 29
organism: Homo sapiens

UNKNOWN_TRANSITION_LEFT__norcotine-RIGHT__4_oxo_4__3_pyridyl__butanamide-_re11
type: Conversion
conversion direction: LEFT_TO_RIGHT
xref: UNKNOWN TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re11 98
participant stoichiometry: PARTICIPANT STOICHIOMETRY re11 99
left: norcotine
interaction type: UNKNOWN_TRANSITION
right: 4-oxo-4-(3-pyridyl)-butanamide

PTHR24300:SF343
type: RelationshipXref
id: PTHR24300:SF343
db: PANTHER Family
relationship type: By Homology

PARTICIPANT STOICHIOMETRY re31 41
type: Stoichiometry
physical entity: 4-(3-pyridyl)-butanoate
stoichiometric coefficient: 1.0

Homo sapiens
type: BioSource
xref: ncbitaxon 9606 7

PARTICIPANT STOICHIOMETRY re31 42
type: Stoichiometry
physical entity: 3-pyridylacetate
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re4 76
type: Stoichiometry
physical entity: nicotine isomethonium ion
stoichiometric coefficient: 1.0

Indolethylamine N-methyltransferase
type: ProteinReference
xref: uniprot O95050 20
organism: Homo sapiens

PARTICIPANT STOICHIOMETRY re4 75
type: Stoichiometry
physical entity: S-adenosyl-homocysteine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re4 74
type: Stoichiometry
physical entity: S-adenosyl-L-methionine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re4 73
type: Stoichiometry
physical entity: nicotine
stoichiometric coefficient: 1.0

norcotinine
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

2-hydroxynicotine
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

UDP-glucuronosyltransferase 1-4
type: ProteinReference
xref: PTHR48050:SF12
xref: uniprot P22310 23
organism: Homo sapiens

PARTICIPANT STOICHIOMETRY re6 57
type: Stoichiometry
physical entity: nicotine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re6 58
type: Stoichiometry
physical entity: UDP-D-glucuronate
stoichiometric coefficient: 1.0

CATALYSIS
type: Catalysis
controlled: STATE_TRANSITION_LEFT__O2-_NADPH-_N_hydroxymethyl_norcotinine-RIGHT__NADP_PLUS_-_H2O-_norcotinine-_re26
controller: CYP2A6

PARTICIPANT STOICHIOMETRY re6 59
type: Stoichiometry
physical entity: UDP
stoichiometric coefficient: 1.0

CATALYSIS
type: Catalysis
controlled: STATE_TRANSITION_LEFT__NADPH-_H2O-_nicotine-RIGHT__NADP_PLUS_-_2_hydroxynicotine-_O2-_re7
controller: CYP2A6

PARTICIPANT STOICHIOMETRY re30 44
type: Stoichiometry
physical entity: 4-(3-pyridyl)-butanoate
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re30 43
type: Stoichiometry
physical entity: 4-(3-pyridyl)-3-butanoate
stoichiometric coefficient: 1.0

PTHR23023:SF44
type: RelationshipXref
id: PTHR23023:SF44
db: PANTHER Family
relationship type: By Homology

3-pyridylacetate
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

ncbitaxon 10116 16
type: UnificationXref
id: 10116
db: ncbitaxon

CYP2A6
type: Protein
entity reference: CYP2A6
comment: SPECIES_TYPE=PROTEIN

STATE_TRANSITION_LEFT__O2-_NADPH-_cotinine-RIGHT__NADP_PLUS_-_H2O-_N_hydroxymethyl_norcotinine-_re25
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re25 119
participant stoichiometry: PARTICIPANT STOICHIOMETRY re25 120
participant stoichiometry: PARTICIPANT STOICHIOMETRY re25 115
participant stoichiometry: PARTICIPANT STOICHIOMETRY re25 118
participant stoichiometry: PARTICIPANT STOICHIOMETRY re25 116
participant stoichiometry: PARTICIPANT STOICHIOMETRY re25 117
left: NADPH
left: cotinine
left: O2
interaction type: STATE_TRANSITION
right: H2O
right: N-hydroxymethyl-norcotinine
right: NADP+

eco ECO:0000304 8
type: UnificationXref
id: ECO:0000304
db: eco

PARTICIPANT STOICHIOMETRY re28 105
type: Stoichiometry
physical entity: 4-oxo-4-(3-pyridyl)-butanoate
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re28 106
type: Stoichiometry
physical entity: 4-hydroxy-4-(3-pyridyl)-butanoate
stoichiometric coefficient: 1.0

UGT1A4
type: ProteinReference
xref: P05982
standard name: UDP glycosytransferase 1, polypeptide A4
comment: ENTITY_REFERENCE_PROTEIN_TYPE=GENERIC
comment: ENTITY_REFERENCE_NOTES= Long Name: UDP glycosytransferase 1, polypeptide A4 Synonym: Synonym not specified Accession: P05982
comment: ENTITY_REFERENCE_ID_DESC=Nicotine_degradation.PROTEIN.GENERIC.UGT1A4
member entity reference: UDP-glucuronosyltransferase
member entity reference: UDP-glucuronosyltransferase 1-4
member entity reference: UDP-glucuronosyltransferase 1-3
member entity reference: UDP-glucuronosyltransferase 1-5

ncbitaxon 9544 3
type: UnificationXref
id: 9544
db: ncbitaxon

PTHR48050:SF12
type: RelationshipXref
id: PTHR48050:SF12
db: PANTHER Family
relationship type: By Homology

FMO3
type: Protein
entity reference: FMO3
comment: SPECIES_TYPE=PROTEIN

uniprot A0A2I3SI43 21
type: UnificationXref
id: A0A2I3SI43
db: uniprot

PARTICIPANT STOICHIOMETRY re6 60
type: Stoichiometry
physical entity: nicotine-glucuronide
stoichiometric coefficient: 1.0

UNKNOWN_TRANSITION_LEFT__4__methylamino__1__3_pyridyl__1_butanone-RIGHT__4_oxo_4__3_pyridyl__butanoate-_re13
type: Conversion
conversion direction: LEFT_TO_RIGHT
xref: UNKNOWN TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re13 95
participant stoichiometry: PARTICIPANT STOICHIOMETRY re13 94
left: 4-(methylamino)-1-(3-pyridyl)-1-butanone
interaction type: UNKNOWN_TRANSITION
right: 4-oxo-4-(3-pyridyl)-butanoate

PARTICIPANT STOICHIOMETRY re27 107
type: Stoichiometry
physical entity: 4-oxo-4-(3-pyridyl)-N-methylbutanamide
stoichiometric coefficient: 1.0

4-hydroxy-4-(3-pyridyl)-butanoate
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

PARTICIPANT STOICHIOMETRY re27 108
type: Stoichiometry
physical entity: 4-oxo-4-(3-pyridyl)-butanoate
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re10 100
type: Stoichiometry
physical entity: H2O
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re10 101
type: Stoichiometry
physical entity: nornicotine
stoichiometric coefficient: 1.0

UNKNOWN_TRANSITION_LEFT__2_hydroxynicotine-RIGHT__4__methylamino__1__3_pyridyl__1_butanone-_re8
type: Conversion
conversion direction: LEFT_TO_RIGHT
xref: UNKNOWN TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re8 50
participant stoichiometry: PARTICIPANT STOICHIOMETRY re8 49
left: 2-hydroxynicotine
interaction type: UNKNOWN_TRANSITION
right: 4-(methylamino)-1-(3-pyridyl)-1-butanone

nicotine-_DELTA_1 5-iminium ion
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

uniprot P11509 28
type: UnificationXref
id: P11509
db: uniprot

PARTICIPANT STOICHIOMETRY re32 40
type: Stoichiometry
physical entity: 4-oxo-4-(3-pyridyl)-butanamide
stoichiometric coefficient: 1.0

Dimethylaniline monooxygenase [N-oxide-forming] 3
type: ProteinReference
xref: uniprot Q9EQ76 15
organism: Rattus norvegicus

STATE_TRANSITION_LEFT__O2-_NADPH-_cotinine-RIGHT__NADP_PLUS_-_trans_3_QUOTE_SINGLE_hydroxycotinine-_H2O-_re19
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re19 63
participant stoichiometry: PARTICIPANT STOICHIOMETRY re19 65
participant stoichiometry: PARTICIPANT STOICHIOMETRY re19 62
participant stoichiometry: PARTICIPANT STOICHIOMETRY re19 64
participant stoichiometry: PARTICIPANT STOICHIOMETRY re19 66
participant stoichiometry: PARTICIPANT STOICHIOMETRY re19 61
left: NADPH
left: cotinine
left: O2
interaction type: STATE_TRANSITION
right: H2O
right: trans-3'-hydroxycotinine
right: NADP+

PARTICIPANT STOICHIOMETRY re8 49
type: Stoichiometry
physical entity: 2-hydroxynicotine
stoichiometric coefficient: 1.0

S-adenosyl-homocysteine
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

uniprot O95050 20
type: UnificationXref
id: O95050
db: uniprot

PARTICIPANT STOICHIOMETRY re35 31
type: Stoichiometry
physical entity: trans-3'-hydroxycotinine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re35 32
type: Stoichiometry
physical entity: UDP-D-glucuronate
stoichiometric coefficient: 1.0

UNKNOWN_TRANSITION
type: InteractionVocabulary

Macaca mulatta
type: BioSource
xref: ncbitaxon 9544 3

PARTICIPANT STOICHIOMETRY re25 120
type: Stoichiometry
physical entity: N-hydroxymethyl-norcotinine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re32 39
type: Stoichiometry
physical entity: norcotinine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re11 99
type: Stoichiometry
physical entity: 4-oxo-4-(3-pyridyl)-butanamide
stoichiometric coefficient: 1.0

uniprot Q7YS44 11
type: UnificationXref
id: Q7YS44
db: uniprot

PARTICIPANT STOICHIOMETRY re11 98
type: Stoichiometry
physical entity: norcotine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re10 102
type: Stoichiometry
physical entity: norcotine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re35 34
type: Stoichiometry
physical entity: trans-3'-hydroxycotinine O-glucuronide
stoichiometric coefficient: 1.0

INMT
type: ProteinReference
xref: P05981
standard name: indolethylamine N-methyltransferase
comment: ENTITY_REFERENCE_PROTEIN_TYPE=GENERIC
comment: ENTITY_REFERENCE_ID_DESC=Nicotine_degradation.PROTEIN.GENERIC.INMT
comment: ENTITY_REFERENCE_NOTES= Long Name: indolethylamine N-methyltransferase Synonym: Synonym not specified Accession: P05981
member entity reference: Indolethylamine N-methyltransferase

uniprot F7HQX7 2
type: UnificationXref
id: F7HQX7
db: uniprot

PARTICIPANT STOICHIOMETRY re35 33
type: Stoichiometry
physical entity: UDP
stoichiometric coefficient: 1.0

TAS
type: EvidenceCodeVocabulary
xref: eco ECO:0000304 8

STATE_TRANSITION_LEFT__O2-_NADPH-_N_hydroxymethyl_norcotinine-RIGHT__NADP_PLUS_-_H2O-_norcotinine-_re26
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re26 113
participant stoichiometry: PARTICIPANT STOICHIOMETRY re26 110
participant stoichiometry: PARTICIPANT STOICHIOMETRY re26 111
participant stoichiometry: PARTICIPANT STOICHIOMETRY re26 109
participant stoichiometry: PARTICIPANT STOICHIOMETRY re26 114
participant stoichiometry: PARTICIPANT STOICHIOMETRY re26 112
left: NADPH
left: O2
left: N-hydroxymethyl-norcotinine
interaction type: STATE_TRANSITION
right: H2O
right: norcotinine
right: NADP+

PARTICIPANT STOICHIOMETRY re9 46
type: Stoichiometry
physical entity: nicotine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re9 45
type: Stoichiometry
physical entity: H2O
stoichiometric coefficient: 1.0

cotinine N-oxide
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

PARTICIPANT STOICHIOMETRY re9 48
type: Stoichiometry
physical entity: nornicotine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re9 47
type: Stoichiometry
physical entity: formaldehyde
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re25 119
type: Stoichiometry
physical entity: H2O
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re25 118
type: Stoichiometry
physical entity: NADP+
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re25 117
type: Stoichiometry
physical entity: cotinine
stoichiometric coefficient: 1.0

S-adenosyl-L-methionine
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

NADP+
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

PARTICIPANT STOICHIOMETRY re21 129
type: Stoichiometry
physical entity: 5'-hydroxycotinine
stoichiometric coefficient: 1.0

ncbitaxon 9606 7
type: UnificationXref
id: 9606
db: ncbitaxon

cotinine methonium ion
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

UDP-glucuronosyltransferase
type: ProteinReference
xref: PTHR48050:SF12
xref: uniprot F7GW14 22
organism: Macaca mulatta

CATALYSIS
type: Catalysis
controlled: STATE_TRANSITION_LEFT__NADPH-_nicotine-RIGHT__NADP_PLUS_-_nicotine__DELTA_1_5_iminium_ion-_re1
controller: CYP2A6

PARTICIPANT STOICHIOMETRY re25 116
type: Stoichiometry
physical entity: NADPH
stoichiometric coefficient: 1.0

UGT2B7
type: Protein
entity reference: UGT2B7
comment: SPECIES_TYPE=PROTEIN

PARTICIPANT STOICHIOMETRY re25 115
type: Stoichiometry
physical entity: O2
stoichiometric coefficient: 1.0

CATALYSIS
type: Catalysis
controlled: STATE_TRANSITION_LEFT__trans_3_QUOTE_SINGLE_hydroxycotinine-RIGHT__trans_3_QUOTE_SINGLE_hydroxycotinine_N_glucuronide-_re34
controller: UGT1A4

4-oxo-4-(3-pyridyl)-butanamide
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

Cytochrome P450 2A6
type: ProteinReference
xref: PTHR24300:SF343
xref: uniprot P11509 28
organism: Homo sapiens

PARTICIPANT STOICHIOMETRY re8 50
type: Stoichiometry
physical entity: 4-(methylamino)-1-(3-pyridyl)-1-butanone
stoichiometric coefficient: 1.0

cotinine-glucuronide
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

PARTICIPANT STOICHIOMETRY re21 130
type: Stoichiometry
physical entity: 4-oxo-4-(3-pyridyl)-N-methylbutanamide
stoichiometric coefficient: 1.0

uniprot Q95LA1 13
type: UnificationXref
id: Q95LA1
db: uniprot

PARTICIPANT STOICHIOMETRY re5 69
type: Stoichiometry
physical entity: nicotine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re5 68
type: Stoichiometry
physical entity: NADPH
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re5 67
type: Stoichiometry
physical entity: O2
stoichiometric coefficient: 1.0

norcotine
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

Rattus norvegicus
type: BioSource
xref: ncbitaxon 10116 16

PARTICIPANT STOICHIOMETRY re19 63
type: Stoichiometry
physical entity: cotinine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re19 62
type: Stoichiometry
physical entity: NADPH
stoichiometric coefficient: 1.0

4-oxo-4-(3-pyridyl)-N-methylbutanamide
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

PARTICIPANT STOICHIOMETRY re19 61
type: Stoichiometry
physical entity: O2
stoichiometric coefficient: 1.0

CATALYSIS
type: Catalysis
controlled: STATE_TRANSITION_LEFT__nicotine-_S_adenosyl_L_methionine-RIGHT__S_adenosyl_homocysteine-_nicotine_isomethonium_ion-_re4
controller: INMT

Canis lupus familiaris
type: BioSource
xref: ncbitaxon 9615 14

UNKNOWN_TRANSITION_LEFT__4_oxo_4__3_pyridyl__butanamide-RIGHT__4_oxo_4__3_pyridyl__butanoate-_re33
type: Conversion
conversion direction: LEFT_TO_RIGHT
xref: UNKNOWN TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re33 37
participant stoichiometry: PARTICIPANT STOICHIOMETRY re33 38
left: 4-oxo-4-(3-pyridyl)-butanamide
interaction type: UNKNOWN_TRANSITION
right: 4-oxo-4-(3-pyridyl)-butanoate

UDP-glucuronosyltransferase
type: ProteinReference
xref: PTHR48050:SF12
xref: uniprot A0A2I3SI43 21
organism: Pan troglodytes

IDA
type: EvidenceCodeVocabulary

PARTICIPANT STOICHIOMETRY re19 66
type: Stoichiometry
physical entity: H2O
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re19 65
type: Stoichiometry
physical entity: trans-3'-hydroxycotinine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re19 64
type: Stoichiometry
physical entity: NADP+
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re5 71
type: Stoichiometry
physical entity: H2O
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re23 125
type: Stoichiometry
physical entity: cotinine
stoichiometric coefficient: 1.0

Dimethylaniline monooxygenase [N-oxide-forming] 3
type: ProteinReference
xref: uniprot P31513 6
xref: PTHR23023:SF44
organism: Homo sapiens

PARTICIPANT STOICHIOMETRY re5 70
type: Stoichiometry
physical entity: NADP+
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re5 72
type: Stoichiometry
physical entity: nicotine-1-N-oxide
stoichiometric coefficient: 1.0

uniprot P22310 23
type: UnificationXref
id: P22310
db: uniprot

PARTICIPANT STOICHIOMETRY re23 126
type: Stoichiometry
physical entity: cotinine methonium ion
stoichiometric coefficient: 1.0

UNKNOWN_TRANSITION_LEFT__norcotinine-RIGHT__4_oxo_4__3_pyridyl__butanamide-_re32
type: Conversion
conversion direction: LEFT_TO_RIGHT
xref: UNKNOWN TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re32 39
participant stoichiometry: PARTICIPANT STOICHIOMETRY re32 40
left: norcotinine
interaction type: UNKNOWN_TRANSITION
right: 4-oxo-4-(3-pyridyl)-butanamide

Indolethylamine N-methyltransferase
type: ProteinReference
xref: uniprot H2QUD4 19
organism: Pan troglodytes

4-(3-pyridyl)-butanoate
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

PARTICIPANT STOICHIOMETRY re26 111
type: Stoichiometry
physical entity: N-hydroxymethyl-norcotinine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re26 110
type: Stoichiometry
physical entity: NADPH
stoichiometric coefficient: 1.0

nornicotine
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

PARTICIPANT STOICHIOMETRY re26 114
type: Stoichiometry
physical entity: norcotinine
stoichiometric coefficient: 1.0

INMT
type: Protein
entity reference: INMT
comment: SPECIES_TYPE=PROTEIN

Cytochrome P450 2A13
type: ProteinReference
xref: uniprot Q16696 30
organism: Homo sapiens

PARTICIPANT STOICHIOMETRY re26 113
type: Stoichiometry
physical entity: H2O
stoichiometric coefficient: 1.0

4-(3-pyridyl)-3-butanoate
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

Dimethylaniline monooxygenase [N-oxide-forming] 3
type: ProteinReference
xref: PTHR23023:SF44
xref: uniprot Q7YS44 11
organism: Pan troglodytes

PARTICIPANT STOICHIOMETRY re26 112
type: Stoichiometry
physical entity: NADP+
stoichiometric coefficient: 1.0

CATALYSIS
type: Catalysis
controlled: STATE_TRANSITION_LEFT__O2-_H2O-_nicotine__DELTA_1_5_iminium_ion-RIGHT__H2O2-_cotinine-_re2
controller: AOX1

STATE_TRANSITION_LEFT__O2-_NADPH-_cotinine-RIGHT__NADP_PLUS_-_5_QUOTE_SINGLE_hydroxycotinine-_H2O-_re20
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re20 132
participant stoichiometry: PARTICIPANT STOICHIOMETRY re20 136
participant stoichiometry: PARTICIPANT STOICHIOMETRY re20 135
participant stoichiometry: PARTICIPANT STOICHIOMETRY re20 131
participant stoichiometry: PARTICIPANT STOICHIOMETRY re20 134
participant stoichiometry: PARTICIPANT STOICHIOMETRY re20 133
left: NADPH
left: cotinine
left: O2
interaction type: STATE_TRANSITION
right: H2O
right: 5'-hydroxycotinine
right: NADP+

nicotine-1-N-oxide
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

uniprot P35504 25
type: UnificationXref
id: P35504
db: uniprot

STATE_TRANSITION
type: InteractionVocabulary

STATE_TRANSITION
type: RelationshipTypeVocabulary

4-(methylamino)-1-(3-pyridyl)-1-butanone
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

Uncharacterized protein
type: ProteinReference
xref: uniprot F7GYG0 27
organism: Macaca mulatta

UGT1A4
type: Protein
entity reference: UGT1A4
comment: SPECIES_TYPE=PROTEIN

PARTICIPANT STOICHIOMETRY re26 109
type: Stoichiometry
physical entity: O2
stoichiometric coefficient: 1.0

UNKNOWN_TRANSITION_LEFT__4_oxo_4__3_pyridyl__butanamide-RIGHT__4_oxo_4__3_pyridyl__butanoate-_re12
type: Conversion
conversion direction: LEFT_TO_RIGHT
xref: UNKNOWN TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re12 97
participant stoichiometry: PARTICIPANT STOICHIOMETRY re12 96
left: 4-oxo-4-(3-pyridyl)-butanamide
interaction type: UNKNOWN_TRANSITION
right: 4-oxo-4-(3-pyridyl)-butanoate

Dimethylaniline monooxygenase [N-oxide-forming] 3
type: ProteinReference
xref: uniprot Q95LA1 13
organism: Canis lupus familiaris

nicotine
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

STATE_TRANSITION_LEFT__5_QUOTE_SINGLE_hydroxycotinine-RIGHT__4_oxo_4__3_pyridyl__N_methylbutanamide-_re21
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re21 130
participant stoichiometry: PARTICIPANT STOICHIOMETRY re21 129
left: 5'-hydroxycotinine
interaction type: STATE_TRANSITION
right: 4-oxo-4-(3-pyridyl)-N-methylbutanamide

N-hydroxymethyl-norcotinine
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

UNKNOWN_TRANSITION_LEFT__H2O-_nornicotine-RIGHT__norcotine-_re10
type: Conversion
conversion direction: LEFT_TO_RIGHT
xref: UNKNOWN TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re10 101
participant stoichiometry: PARTICIPANT STOICHIOMETRY re10 102
participant stoichiometry: PARTICIPANT STOICHIOMETRY re10 100
left: H2O
left: nornicotine
interaction type: UNKNOWN_TRANSITION
right: norcotine

uniprot Q9EQ76 15
type: UnificationXref
id: Q9EQ76
db: uniprot

PARTICIPANT STOICHIOMETRY re1 90
type: Stoichiometry
physical entity: NADP+
stoichiometric coefficient: 1.0

STATE_TRANSITION_LEFT__O2-_NADPH-_nicotine-RIGHT__NADP_PLUS_-_H2O-_nicotine_1_N_oxide-_re5
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re5 70
participant stoichiometry: PARTICIPANT STOICHIOMETRY re5 67
participant stoichiometry: PARTICIPANT STOICHIOMETRY re5 72
participant stoichiometry: PARTICIPANT STOICHIOMETRY re5 68
participant stoichiometry: PARTICIPANT STOICHIOMETRY re5 71
participant stoichiometry: PARTICIPANT STOICHIOMETRY re5 69
left: NADPH
left: O2
left: nicotine
interaction type: STATE_TRANSITION
right: H2O
right: nicotine-1-N-oxide
right: NADP+

PARTICIPANT STOICHIOMETRY re1 91
type: Stoichiometry
physical entity: nicotine-_DELTA_1 5-iminium ion
stoichiometric coefficient: 1.0

ncbitaxon 10090 10
type: UnificationXref
id: 10090
db: ncbitaxon

nicotine-glucuronide
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

PANTHER Pathway P05914 1
type: UnificationXref
id: P05914
db: PANTHER Pathway

NADPH
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

5'-hydroxycotinine
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

CYP2A6
type: ProteinReference
xref: P05984
standard name: cytochrome P450 subfamily IIA polypeptide 6
comment: ENTITY_REFERENCE_NOTES= Long Name: cytochrome P450 subfamily IIA polypeptide 6 Synonym: Coumarin 7-hydroxylase Accession: P05984
comment: ENTITY_REFERENCE_PROTEIN_TYPE=GENERIC
comment: ENTITY_REFERENCE_ID_DESC=Nicotine_degradation.PROTEIN.GENERIC.CYP2A6
member entity reference: Uncharacterized protein
member entity reference: Cytochrome P450 2A13
member entity reference: Cytochrome P450 2A6
member entity reference: Cytochrome P450 2A7

cotinine
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

PARTICIPANT STOICHIOMETRY re2 81
type: Stoichiometry
physical entity: O2
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re2 82
type: Stoichiometry
physical entity: H2O
stoichiometric coefficient: 1.0

uniprot P97501 9
type: UnificationXref
id: P97501
db: uniprot

PARTICIPANT STOICHIOMETRY re2 83
type: Stoichiometry
physical entity: nicotine-_DELTA_1 5-iminium ion
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re2 84
type: Stoichiometry
physical entity: H2O2
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re2 85
type: Stoichiometry
physical entity: cotinine
stoichiometric coefficient: 1.0

eco ECO:0000250 4
type: UnificationXref
id: ECO:0000250
db: eco

Nicotine_degradation
type: Pathway
pathway component: STATE_TRANSITION_LEFT__O2-_NADPH-_N_hydroxymethyl_norcotinine-RIGHT__NADP_PLUS_-_H2O-_norcotinine-_re26
pathway component: STATE_TRANSITION_LEFT__O2-_NADPH-_nicotine-RIGHT__NADP_PLUS_-_H2O-_nicotine_1_N_oxide-_re5
pathway component: UNKNOWN_TRANSITION_LEFT__4_oxo_4__3_pyridyl__N_methylbutanamide-RIGHT__4_oxo_4__3_pyridyl__butanoate-_re27
pathway component: STATE_TRANSITION_LEFT__nicotine-_S_adenosyl_L_methionine-RIGHT__S_adenosyl_homocysteine-_nicotine_isomethonium_ion-_re4
pathway component: STATE_TRANSITION_LEFT__trans_3_QUOTE_SINGLE_hydroxycotinine-_UDP_D_glucuronate-RIGHT__UDP-_trans_3_QUOTE_SINGLE_hydroxycotinine_O_glucuronide-_re35
pathway component: UNKNOWN_TRANSITION_LEFT__norcotine-RIGHT__4_oxo_4__3_pyridyl__butanamide-_re11
pathway component: UNKNOWN_TRANSITION_LEFT__H2O-_nicotine-RIGHT__formaldehyde-_nornicotine-_re9
pathway component: UNKNOWN_TRANSITION_LEFT__4_oxo_4__3_pyridyl__butanoate-RIGHT__4_hydroxy_4__3_pyridyl__butanoate-_re14
pathway component: UNKNOWN_TRANSITION_LEFT__2_hydroxynicotine-RIGHT__4__methylamino__1__3_pyridyl__1_butanone-_re8
pathway component: UNKNOWN_TRANSITION_LEFT__4_hydroxy_4__3_pyridyl__butanoate-RIGHT__4__3_pyridyl__3_butanoate-_re29
pathway component: STATE_TRANSITION_LEFT__cotinine-RIGHT__cotinine_N_oxide-_re22
pathway component: STATE_TRANSITION_LEFT__O2-_NADPH-_cotinine-RIGHT__NADP_PLUS_-_trans_3_QUOTE_SINGLE_hydroxycotinine-_H2O-_re19
pathway component: UNKNOWN_TRANSITION_LEFT__4_hydroxy_4__3_pyridyl__butanoate-RIGHT__4__3_pyridyl__3_butanoate-_re15
pathway component: UNKNOWN_TRANSITION_LEFT__H2O-_nornicotine-RIGHT__norcotine-_re10
pathway component: UNKNOWN_TRANSITION_LEFT__4_oxo_4__3_pyridyl__butanoate-RIGHT__4_hydroxy_4__3_pyridyl__butanoate-_re28
pathway component: STATE_TRANSITION_LEFT__cotinine-_UDP_D_glucuronate-RIGHT__UDP-_cotinine_glucuronide-_re24
pathway component: UNKNOWN_TRANSITION_LEFT__4__methylamino__1__3_pyridyl__1_butanone-RIGHT__4_oxo_4__3_pyridyl__butanoate-_re13
pathway component: STATE_TRANSITION_LEFT__trans_3_QUOTE_SINGLE_hydroxycotinine-RIGHT__trans_3_QUOTE_SINGLE_hydroxycotinine_N_glucuronide-_re34
pathway component: STATE_TRANSITION_LEFT__NADPH-_H2O-_nicotine-RIGHT__NADP_PLUS_-_2_hydroxynicotine-_O2-_re7
pathway component: STATE_TRANSITION_LEFT__O2-_NADPH-_cotinine-RIGHT__NADP_PLUS_-_5_QUOTE_SINGLE_hydroxycotinine-_H2O-_re20
pathway component: STATE_TRANSITION_LEFT__5_QUOTE_SINGLE_hydroxycotinine-RIGHT__4_oxo_4__3_pyridyl__N_methylbutanamide-_re21
pathway component: STATE_TRANSITION_LEFT__cotinine-RIGHT__cotinine_methonium_ion-_re23
pathway component: UNKNOWN_TRANSITION_LEFT__4__3_pyridyl__butanoate-RIGHT__3_pyridylacetate-_re31
pathway component: UNKNOWN_TRANSITION_LEFT__4__3_pyridyl__3_butanoate-RIGHT__4__3_pyridyl__butanoate-_re30
pathway component: UNKNOWN_TRANSITION_LEFT__norcotinine-RIGHT__4_oxo_4__3_pyridyl__butanamide-_re32
pathway component: STATE_TRANSITION_LEFT__O2-_NADPH-_cotinine-RIGHT__NADP_PLUS_-_H2O-_N_hydroxymethyl_norcotinine-_re25
pathway component: STATE_TRANSITION_LEFT__nicotine-_UDP_D_glucuronate-RIGHT__UDP-_nicotine_glucuronide-_re6
pathway component: UNKNOWN_TRANSITION_LEFT__4__3_pyridyl__3_butanoate-RIGHT__4__3_pyridyl__butanoate-_re16
pathway component: STATE_TRANSITION_LEFT__O2-_H2O-_nicotine__DELTA_1_5_iminium_ion-RIGHT__H2O2-_cotinine-_re2
pathway component: UNKNOWN_TRANSITION_LEFT__4_oxo_4__3_pyridyl__butanamide-RIGHT__4_oxo_4__3_pyridyl__butanoate-_re12
pathway component: UNKNOWN_TRANSITION_LEFT__4_oxo_4__3_pyridyl__butanamide-RIGHT__4_oxo_4__3_pyridyl__butanoate-_re33
pathway component: STATE_TRANSITION_LEFT__NADPH-_nicotine-RIGHT__NADP_PLUS_-_nicotine__DELTA_1_5_iminium_ion-_re1
pathway component: UNKNOWN_TRANSITION_LEFT__4__3_pyridyl__butanoate-RIGHT__3_pyridylacetate-_re17
xref: PANTHER Pathway P05914 1
comment: MODEL_NOTES= Nicotine is the principal alkaloid in the leaves of commercially used tobacco (Nicotiana tabacum and N. rustica). Nicotine in tobacco leaves and in plant-derived preparations is mostly in the (S)-nicotine isomeric form. However, tobacco smoke contains up to 10% (R)-nicotine, probably due to racemization during combustion. Nicotine is the addictive compound in tobacco and is a commonly used psychoactive drug. It enters the body by systemic absorption through cigarette smoking, oral snuff, pipe tobacco, cigars and chewing tobacco use. It can also enter in purified form as a medication. Nicotine has complex physiological effects. In cigarette smoke nicotine is carried into the body on particulate matter. It is rapidly absorbed in the small airways and alveoli of the lung. In this neutral pH environment, it is un-ionized, soluble, and can be transferred across cell membranes and into the blood. It moves into the pulmonary venous circulation, to the left ventricle of the heart, and into the systemic arterial circulation. It travels to the brain within seconds where it binds to nicotinic cholinergic receptors and activates the dopaminergic reward system. Other forms of nicotine (such as nicotine gum, transdermal patch, inhaler, lozenges, and sublingual tablets) are usually buffered at alkaline pH and quickly traverse cell membranes, but most reach the blood and brain more slowly. They are less likely to cause addiction due to the delayed reward of nicotine effects. In humans, the primary site of nicotine metabolism is the liver. There is little evidence in the literature for any extrahepatic metabolism, despite the presence of isoforms of nicotine metabolizing enzymes in other tissues. Nicotine and its metabolites are excreted in urine, where they have been analyzed and quantitated. These data showed considerable interindividual variability in the amount of each metabolite produced. Cotinine is the primary metabolite of nicotine and is found in the urine of s…

STATE_TRANSITION_LEFT__trans_3_QUOTE_SINGLE_hydroxycotinine-_UDP_D_glucuronate-RIGHT__UDP-_trans_3_QUOTE_SINGLE_hydroxycotinine_O_glucuronide-_re35
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re35 33
participant stoichiometry: PARTICIPANT STOICHIOMETRY re35 32
participant stoichiometry: PARTICIPANT STOICHIOMETRY re35 34
participant stoichiometry: PARTICIPANT STOICHIOMETRY re35 31
left: trans-3'-hydroxycotinine
left: UDP-D-glucuronate
interaction type: STATE_TRANSITION
right: trans-3'-hydroxycotinine O-glucuronide
right: UDP

CATALYSIS
type: Catalysis
controlled: STATE_TRANSITION_LEFT__nicotine-_UDP_D_glucuronate-RIGHT__UDP-_nicotine_glucuronide-_re6
controller: UGT1A4

PARTICIPANT STOICHIOMETRY re1 89
type: Stoichiometry
physical entity: nicotine
stoichiometric coefficient: 1.0

uniprot P20853 29
type: UnificationXref
id: P20853
db: uniprot

UGT2B7
type: ProteinReference
xref: P05980
standard name: UDP glycosyltransferase 2, member B7
comment: ENTITY_REFERENCE_ID_DESC=Nicotine_degradation.PROTEIN.GENERIC.UGT2B7
comment: ENTITY_REFERENCE_PROTEIN_TYPE=GENERIC
comment: ENTITY_REFERENCE_NOTES= Long Name: UDP glycosyltransferase 2, member B7 Synonym: uridine diphosphate glycosyltransferase 2, member B7 Accession: P05980
member entity reference: UDP-glucuronosyltransferase 2B7

AOX1
type: Protein
comment: SPECIES_TYPE=PROTEIN

PARTICIPANT STOICHIOMETRY re1 88
type: Stoichiometry
physical entity: NADPH
stoichiometric coefficient: 1.0

uniprot H2QUD4 19
type: UnificationXref
id: H2QUD4
db: uniprot

ncbitaxon 9598 12
type: UnificationXref
id: 9598
db: ncbitaxon

STATE_TRANSITION_LEFT__trans_3_QUOTE_SINGLE_hydroxycotinine-RIGHT__trans_3_QUOTE_SINGLE_hydroxycotinine_N_glucuronide-_re34
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re34 36
participant stoichiometry: PARTICIPANT STOICHIOMETRY re34 35
left: trans-3'-hydroxycotinine
interaction type: STATE_TRANSITION
right: trans-3'-hydroxycotinine N-glucuronide

FMO3
type: ProteinReference
xref: P05979
standard name: Flavin-containing monooxygenase
comment: ENTITY_REFERENCE_PROTEIN_TYPE=GENERIC
comment: ENTITY_REFERENCE_ID_DESC=Nicotine_degradation.PROTEIN.GENERIC.FMO3
comment: ENTITY_REFERENCE_NOTES= Long Name: Flavin-containing monooxygenase Synonym: Dimethylaniline N-oxidase,Dimethylaniline monooxygenase (N-oxide-forming) Accession: P05979
member entity reference: Dimethylaniline monooxygenase [N-oxide-forming] 3
member entity reference: Dimethylaniline monooxygenase [N-oxide-forming]

CATALYSIS
type: Catalysis
controlled: STATE_TRANSITION_LEFT__trans_3_QUOTE_SINGLE_hydroxycotinine-_UDP_D_glucuronate-RIGHT__UDP-_trans_3_QUOTE_SINGLE_hydroxycotinine_O_glucuronide-_re35
controller: UGT2B7