PARTICIPANT STOICHIOMETRY re5 9
type: Stoichiometry
physical entity: m-chlorohippurate
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re5 6
type: Stoichiometry
physical entity: m-chlorobenzoate
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re5 7
type: Stoichiometry
physical entity: glycine
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re5 8
type: Stoichiometry
physical entity: H2O
stoichiometric coefficient: 1.0

erythrohydrobupropion
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

CATALYSIS
type: Catalysis
controlled: STATE_TRANSITION_LEFT__NADPH-_O2-_bupropion-RIGHT__H2O-_hydroxybupropion-_NADP_PLUS_-_re2
controller: Cytochrome P450 2B6

PARTICIPANT STOICHIOMETRY re4 10
type: Stoichiometry
physical entity: bupropion
stoichiometric coefficient: 1.0

eco ECO:0000304 4
type: UnificationXref
id: ECO:0000304
db: eco

PARTICIPANT STOICHIOMETRY re4 11
type: Stoichiometry
physical entity: m-chlorobenzoate
stoichiometric coefficient: 1.0

threohydrobupropion
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

PTHR24300:SF153
type: RelationshipXref
id: PTHR24300:SF153
db: PANTHER Family
relationship type: By Homology

STATE_TRANSITION
type: InteractionVocabulary

STATE_TRANSITION
type: RelationshipTypeVocabulary

m-chlorobenzoate
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

STATE_TRANSITION_LEFT__bupropion-RIGHT__m_chlorobenzoate-_re4
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re4 11
participant stoichiometry: PARTICIPANT STOICHIOMETRY re4 10
left: bupropion
interaction type: STATE_TRANSITION
right: m-chlorobenzoate

H2O
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

hydroxybupropion
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

NADPH
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

STATE_TRANSITION_LEFT__NADPH-_O2-_bupropion-RIGHT__H2O-_hydroxybupropion-_NADP_PLUS_-_re2
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re2 19
participant stoichiometry: PARTICIPANT STOICHIOMETRY re2 18
participant stoichiometry: PARTICIPANT STOICHIOMETRY re2 16
participant stoichiometry: PARTICIPANT STOICHIOMETRY re2 15
participant stoichiometry: PARTICIPANT STOICHIOMETRY re2 14
participant stoichiometry: PARTICIPANT STOICHIOMETRY re2 17
left: O2
left: NADPH
left: bupropion
interaction type: STATE_TRANSITION
right: H2O
right: hydroxybupropion
right: NADP+

m-chlorohippurate
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

PANTHER Pathway P05729 1
type: UnificationXref
id: P05729
db: PANTHER Pathway

PARTICIPANT STOICHIOMETRY re2 19
type: Stoichiometry
physical entity: NADP+
stoichiometric coefficient: 1.0

STATE_TRANSITION_LEFT__bupropion-RIGHT__erythrohydrobupropion-_re3
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re3 13
participant stoichiometry: PARTICIPANT STOICHIOMETRY re3 12
left: bupropion
interaction type: STATE_TRANSITION
right: erythrohydrobupropion

Cytochrome P450 2B6
type: ProteinReference
xref: uniprot P20813 2
xref: PTHR24300:SF153
organism: Homo sapiens

TAS
type: EvidenceCodeVocabulary
xref: eco ECO:0000304 4

Homo sapiens
type: BioSource
xref: ncbitaxon 9606 3

By Homology
type: RelationshipTypeVocabulary

PARTICIPANT STOICHIOMETRY re2 17
type: Stoichiometry
physical entity: H2O
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re2 18
type: Stoichiometry
physical entity: hydroxybupropion
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re2 15
type: Stoichiometry
physical entity: O2
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re2 16
type: Stoichiometry
physical entity: bupropion
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re2 14
type: Stoichiometry
physical entity: NADPH
stoichiometric coefficient: 1.0

ncbitaxon 9606 3
type: UnificationXref
id: 9606
db: ncbitaxon

Cytochrome P450 2B6
type: Protein
entity reference: Cytochrome P450 2B6
comment: SPECIES_TYPE=PROTEIN

STATE_TRANSITION_LEFT__m_chlorobenzoate-_glycine-RIGHT__H2O-_m_chlorohippurate-_re5
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re5 7
participant stoichiometry: PARTICIPANT STOICHIOMETRY re5 6
participant stoichiometry: PARTICIPANT STOICHIOMETRY re5 9
participant stoichiometry: PARTICIPANT STOICHIOMETRY re5 8
left: glycine
left: m-chlorobenzoate
interaction type: STATE_TRANSITION
right: H2O
right: m-chlorohippurate

O2
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

P05742
type: UnificationXref
id: P05742
db: PANTHER Pathway Component

PARTICIPANT STOICHIOMETRY re3 12
type: Stoichiometry
physical entity: bupropion
stoichiometric coefficient: 1.0

PARTICIPANT STOICHIOMETRY re3 13
type: Stoichiometry
physical entity: erythrohydrobupropion
stoichiometric coefficient: 1.0

bupropion
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

PARTICIPANT STOICHIOMETRY re1 20
type: Stoichiometry
physical entity: bupropion
stoichiometric coefficient: 1.0

STATE_TRANSITION_LEFT__bupropion-RIGHT__threohydrobupropion-_re1
type: BiochemicalReaction
conversion direction: LEFT_TO_RIGHT
xref: STATE TRANSITION
participant stoichiometry: PARTICIPANT STOICHIOMETRY re1 21
participant stoichiometry: PARTICIPANT STOICHIOMETRY re1 20
left: bupropion
interaction type: STATE_TRANSITION
right: threohydrobupropion

NADP+
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

PARTICIPANT STOICHIOMETRY re1 21
type: Stoichiometry
physical entity: threohydrobupropion
stoichiometric coefficient: 1.0

glycine
type: SmallMolecule
comment: SPECIES_TYPE=SIMPLE_MOLECULE

uniprot P20813 2
type: UnificationXref
id: P20813
db: uniprot

Cytochrome P450 2B6
type: ProteinReference
xref: P05742
comment: ENTITY_REFERENCE_PROTEIN_TYPE=GENERIC
comment: ENTITY_REFERENCE_NOTES=Long Name: Cytochrome P450 2B6 Synonym: CYP2B6,Cytochrome P450 2B6/bupropion hydroxylase,cytochrome P450, family 2, subfamily B, polypeptide 6 Accession: P05742
comment: ENTITY_REFERENCE_ID_DESC=Bupropion_degradation.PROTEIN.GENERIC.Cytochrome_br_P450 2B6
member entity reference: Cytochrome P450 2B6

Bupropion_degradation
type: Pathway
pathway component: STATE_TRANSITION_LEFT__bupropion-RIGHT__erythrohydrobupropion-_re3
pathway component: STATE_TRANSITION_LEFT__bupropion-RIGHT__m_chlorobenzoate-_re4
pathway component: STATE_TRANSITION_LEFT__bupropion-RIGHT__threohydrobupropion-_re1
pathway component: STATE_TRANSITION_LEFT__m_chlorobenzoate-_glycine-RIGHT__H2O-_m_chlorohippurate-_re5
pathway component: STATE_TRANSITION_LEFT__NADPH-_O2-_bupropion-RIGHT__H2O-_hydroxybupropion-_NADP_PLUS_-_re2
xref: PANTHER Pathway P05729 1
comment: MODEL_NOTES=Bupropion is a drug in the amino ketone class that was developed for use as an antidepressant. It is marketed as bupropion hydrochloride under the brand name Wellbutrin (GlaxoSmithKline). Its exact mechanism of action as an antidepressant is unknown. Bupropion has also been found to be useful in smoking cessation therapy, particularly in combination with nicotine replacement therapy and behavioral therapy. It is marketed for smoking cessation therapy as bupropion hydrochloride, sustained-release formulation, under the brand name Zyban (GlaxoSmithKline). It can block the reuptake of dopamine and norepinephrine in the brain and may be a brain nicotinic acetylcholine receptor antagonist, suggesting its use in smoking cessation therapy.######In humans given an oral dose of bupropion, radioimmunoassay indicated rapid absorption and appearance of the drug in plasma. Plasma levels fall as the drug is extensively metabolized in the liver. Approximately 80% of a dose of bupropion is excreted as metabolites in urine, with less than 1% excreted as unchanged bupropion. Bupropion is metabolized to basic and acidic metabolites in humans. Major basic metabolites include hydroxybupropion, and the amino alcohol isomers threohydrobupropion and erythrohydrobupropion. Two acidic metabolites, m-chlorobenzoic acid and m-chlorohippuric acid, have also been identified. Differences in bupropion metabolism between humans and animals have been described. Humans given an oral dose of 14C-bupropion excreted relatively more basic metabolites than rats, which excreted predominantly acidic metabolites. Human plasma contained relatively more hydroxybupropion than bupropion, while the opposite was true for rat plasma.######Hydroxybupropion is the main physiologically active metabolite in humans. The involvement of the cytochrome P450 isoform 2B6 in this hydroxylation reaction has been shown. The formation of threohydrobupropion and erythrohydrobupropion involves modification of the amino…