Reference/ChemSpider 17215925
type: UnificationXref
id: 17215925
db: ChemSpider

Reference/PubChem-compound 6022
type: UnificationXref
id: 6022
db: PubChem-compound

Doxorubicin-semiquinone
type: SmallMolecule
cellular location: Mitochondrion
entity reference: Doxorubicin-semiquinone

Reference/ChemSpider 937
type: UnificationXref
id: 937
db: ChemSpider

Reference/ChemSpider 8652398
type: UnificationXref
id: 8652398
db: ChemSpider

Compound/PW C040616 Cytoplasm/Stoichiometry/1.0
type: Stoichiometry
physical entity: Doxorubicin-semiquinone
stoichiometric coefficient: 1.0

NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial
type: Protein
cellular location: Endoplasmic Reticulum Membrane
entity reference: NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial

Doxorubicin
type: SmallMolecule
cellular location: Mitochondrion
entity reference: Doxorubicin

Reference/PubChem-compound 439153
type: UnificationXref
id: 439153
db: PubChem-compound

ChemicalStructure/PW C001420
type: ChemicalStructure
structure format: SMILES
structure data: O

Reference/HMDB HMDB0060822
type: UnificationXref
id: HMDB0060822
db: HMDB

Compound/PW C000143 Cytoplasm/Stoichiometry/1.0
type: Stoichiometry
physical entity: NADP
stoichiometric coefficient: 1.0

Doxorubicin
type: SmallMolecule
cellular location: Endoplasmic Reticulum Membrane
entity reference: Doxorubicin

Reference/HMDB HMDB0041884
type: UnificationXref
id: HMDB0041884
db: HMDB

Doxorubicin-semiquinone
type: SmallMolecule
cellular location: Mitochondrial Inner Membrane
entity reference: Doxorubicin-semiquinone

Compound/PW C009432 Extracellular Space/Stoichiometry/1.0
type: Stoichiometry
physical entity: Doxorubicin
stoichiometric coefficient: 1.0

Reference/UniProt Q92887
type: UnificationXref
id: Q92887
db: UniProt

NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial
type: Protein
cellular location: Mitochondrial Inner Membrane
entity reference: NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial

Reference/HMDB HMDB0000538
type: UnificationXref
id: HMDB0000538
db: HMDB

Compound/PW C040616 Endoplasmic Reticulum Membrane/Stoichiometry/1.0
type: Stoichiometry
physical entity: Doxorubicin-semiquinone
stoichiometric coefficient: 1.0

Doxorubicin-semiquinone
type: SmallMoleculeReference
xref: Reference/HMDB HMDB0060822
chemical formula: C27H33NO11
molecular weight: 547.2054
structure: ChemicalStructure/PW C040616

Reference/BioCyc ATP
type: UnificationXref
id: ATP
db: BioCyc

Doxorubicinol deoxaglycone
type: SmallMoleculeReference
xref: Reference/ChemSpider 23935799
xref: Reference/PubChem-compound 45038813
xref: Reference/HMDB HMDB0061206
chemical formula: C21H20O8
molecular weight: 400.1158
structure: ChemicalStructure/PW C040617

Doxorubicine hydroxyaglycone
type: SmallMoleculeReference
xref: Reference/HMDB HMDB0061231
xref: Reference/PubChem-compound 72401
xref: Reference/ChemSpider 65332
chemical formula: C21H18O9
molecular weight: 414.0951
structure: ChemicalStructure/PW C040618

Compound/PW C009432 Cell Membrane/Stoichiometry/1.0
type: Stoichiometry
physical entity: Doxorubicin
stoichiometric coefficient: 1.0

Doxorubicinol hydroxyaglycone
type: SmallMoleculeReference
xref: Reference/PubChem-compound 10476988
xref: Reference/HMDB HMDB0061232
xref: Reference/ChemSpider 8652398
chemical formula: C21H20O9
molecular weight: 416.11072
structure: ChemicalStructure/PW C040619

Compound/PW C001420 Cell Membrane/Stoichiometry/1.0
type: Stoichiometry
physical entity: Water
stoichiometric coefficient: 1.0

Reference/ChEBI CHEBI 15846
type: UnificationXref
id: CHEBI:15846
db: ChEBI

Reference/SMPDB SMP0000650
type: UnificationXref
id: SMP0000650
db: SMPDB

Reference/BioCyc ADP
type: UnificationXref
id: ADP
db: BioCyc

NADH
type: SmallMolecule
cellular location: Mitochondrial Inner Membrane
entity reference: NADH

Reference/UniProt P29474
type: UnificationXref
id: P29474
db: UniProt

Reference/UniProt Q15311
type: UnificationXref
id: Q15311
db: UniProt

Reference/CELL TYPE ONTOLOGY CL 0000182
type: UnificationXref
id: CL:0000182
db: CELL TYPE ONTOLOGY

Reference/CAS 53-59-8
type: UnificationXref
id: 53-59-8
db: CAS

Reference/BRENDA TISSUE ONTOLOGY BTO 0000759
type: UnificationXref
id: BTO:0000759
db: BRENDA TISSUE ONTOLOGY

NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial
type: Protein
cellular location: Endoplasmic Reticulum Membrane
entity reference: NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial

Compound/PW C001104 Cell Membrane/Stoichiometry/1.0
type: Stoichiometry
physical entity: Phosphate
stoichiometric coefficient: 1.0

Reference/KEGG Compound C01661
type: UnificationXref
id: C01661
db: KEGG Compound

Protein/1543 Cytoplasm/Stoichiometry/2.0
type: Stoichiometry
physical entity: NAD(P)H dehydrogenase [quinone] 1
stoichiometric coefficient: 2.0

Reference/ChemSpider 5742
type: UnificationXref
id: 5742
db: ChemSpider

Reference/ChEBI CHEBI 16474
type: UnificationXref
id: CHEBI:16474
db: ChEBI

Solute carrier family 22 member 16
type: Protein
entity reference: Solute carrier family 22 member 16

ReactionCatalysis1902
type: Catalysis
controller: Carbonyl reductase [NADPH] 3
controlled: Reaction2032
control type: ACTIVATION

Reference/ChemSpider 65332
type: UnificationXref
id: 65332
db: ChemSpider

ReactionCatalysis1901
type: Catalysis
controller: Carbonyl reductase [NADPH] 1
controlled: Reaction2032
control type: ACTIVATION

Compound/PW C040619 Cytoplasm/Stoichiometry/1.0
type: Stoichiometry
physical entity: Doxorubicinol hydroxyaglycone
stoichiometric coefficient: 1.0

Reference/UniProt Q86VW1
type: UnificationXref
id: Q86VW1
db: UniProt

Reference/UniProt P16152
type: UnificationXref
id: P16152
db: UniProt

Reference/ChEBI CHEBI 16908
type: UnificationXref
id: CHEBI:16908
db: ChEBI

Carbonyl reductase [NADPH] 1
type: Protein
cellular location: Cytoplasm
entity reference: Carbonyl reductase [NADPH] 1

Compound/PW C001144 Mitochondrial Inner Membrane/Stoichiometry/1.0
type: Stoichiometry
physical entity: NADH
stoichiometric coefficient: 1.0

Reference/HMDB HMDB0061231
type: UnificationXref
id: HMDB0061231
db: HMDB

Phosphate
type: SmallMolecule
cellular location: Cell Membrane
entity reference: Phosphate

Reference/HMDB HMDB0061232
type: UnificationXref
id: HMDB0061232
db: HMDB

ReactionCatalysis1904
type: Catalysis
controller: Alcohol dehydrogenase [NADP(+)]
controlled: Reaction2032
control type: ACTIVATION

Phosphate
type: SmallMoleculeReference
xref: Reference/KEGG Compound C00009
xref: Reference/PubChem-compound 1061
xref: Reference/CAS 14265-44-2
xref: Reference/HMDB HMDB0001429
xref: Reference/BioCyc CPD-8587
xref: Reference/ChEBI CHEBI 18367
xref: Reference/ChemSpider 1032
chemical formula: H3O4P
molecular weight: 97.9769
structure: ChemicalStructure/PW C001104

ReactionCatalysis1903
type: Catalysis
controller: Aldo-keto reductase family 1 member C3
controlled: Reaction2032
control type: ACTIVATION

Reference/HMDB HMDB0015132
type: UnificationXref
id: HMDB0015132
db: HMDB

Compound/PW C001034 Cell Membrane/Stoichiometry/1.0
type: Stoichiometry
physical entity: Adenosine diphosphate
stoichiometric coefficient: 1.0

ReactionCatalysis1906
type: Catalysis
controller: NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial
controlled: 1.14.13.39
control type: ACTIVATION

ReactionCatalysis1908
type: Catalysis
controller: NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial
controlled: 1.14.13.39
control type: ACTIVATION

ReactionCatalysis1907
type: Catalysis
controller: NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial
controlled: 1.14.13.39
control type: ACTIVATION

ReactionCatalysis1909
type: Catalysis
controller: Nitric-oxide synthase, endothelial
controlled: 1.14.13.39
control type: ACTIVATION

NADPH--cytochrome P450 reductase
type: ProteinReference
xref: Reference/UniProt P16435
organism: Homo sapiens

NAD
type: SmallMolecule
cellular location: Mitochondrial Inner Membrane
entity reference: NAD

Xanthine dehydrogenase/oxidase
type: ProteinReference
xref: Reference/UniProt P47989
organism: Homo sapiens

ReactionCatalysis1913
type: Catalysis
controller: NAD(P)H dehydrogenase [quinone] 1
controlled: 1.14.13.39
control type: ACTIVATION

ATP-binding cassette sub-family G member 2
type: Protein
cellular location: Cell Membrane
entity reference: ATP-binding cassette sub-family G member 2

ReactionCatalysis1912
type: Catalysis
controller: Xanthine dehydrogenase/oxidase
controlled: 1.14.13.39
control type: ACTIVATION

NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial
type: ProteinReference
xref: Reference/UniProt O75251
organism: BiologicalState10

NADPH
type: SmallMoleculeReference
xref: Reference/CAS 53-57-6
xref: Reference/HMDB HMDB0000221
xref: Reference/PubChem-compound 22833512
xref: Reference/BioCyc NADPH
xref: Reference/ChemSpider 17215925
xref: Reference/KEGG Compound C00005
xref: Reference/ChEBI CHEBI 16474
chemical formula: C21H30N7O17P3
molecular weight: 745.0911
structure: ChemicalStructure/PW C000146

NADP
type: SmallMoleculeReference
xref: Reference/KEGG Compound C00006
xref: Reference/CAS 53-59-8
xref: Reference/BioCyc NAD(P)
xref: Reference/HMDB HMDB0000217
xref: Reference/ChEBI CHEBI 18009
xref: Reference/PubChem-compound 5886
xref: Reference/ChemSpider 5675
chemical formula: C21H28N7O17P3
molecular weight: 743.07544
structure: ChemicalStructure/PW C000143

Mitochondrion
type: CellularLocationVocabulary
xref: Reference/GENE ONTOLOGY GO 0005739

ReactionCoupledTransportCatalysis87
type: Catalysis
controller: Multidrug resistance-associated protein 1
controlled: ReactionCoupledTransport72
control type: ACTIVATION

ReactionCoupledTransportCatalysis86
type: Catalysis
controller: Multidrug resistance protein 1
controlled: 3.6.3.44
control type: ACTIVATION

ReactionCoupledTransportCatalysis89
type: Catalysis
controller: ATP-binding cassette sub-family G member 2
controlled: ReactionCoupledTransport74
control type: ACTIVATION

ReactionCoupledTransportCatalysis88
type: Catalysis
controller: Canalicular multispecific organic anion transporter 1
controlled: ReactionCoupledTransport73
control type: ACTIVATION

Reference/BioCyc NADPH
type: UnificationXref
id: NADPH
db: BioCyc

Doxorubicin-semiquinone
type: SmallMolecule
cellular location: Cytoplasm
entity reference: Doxorubicin-semiquinone

Multidrug resistance-associated protein 1
type: Protein
cellular location: Cell Membrane
entity reference: Multidrug resistance-associated protein 1

Reference/UniProt O75306
type: UnificationXref
id: O75306
db: UniProt

TransportCatalysis161
type: Catalysis
controller: RalA-binding protein 1
controlled: Transport199
control type: ACTIVATION

TransportCatalysis160
type: Catalysis
controller: ATP-binding cassette sub-family G member 2
controlled: Transport199
control type: ACTIVATION

NADPH--cytochrome P450 reductase
type: Protein
cellular location: Cytoplasm
entity reference: NADPH--cytochrome P450 reductase

Reference/CAS 58-68-4
type: UnificationXref
id: 58-68-4
db: CAS

Reference/PubChem-compound 31703
type: UnificationXref
id: 31703
db: PubChem-compound

Protein/872 Cytoplasm/Stoichiometry/2.0
type: Stoichiometry
physical entity: Nitric oxide synthase, endothelial
stoichiometric coefficient: 2.0

ChemicalStructure/PW C001104
type: ChemicalStructure
structure format: SMILES
structure data: OP(O)(O)=O

Compound/PW C000146 Cytoplasm/Stoichiometry/1.0
type: Stoichiometry
physical entity: NADPH
stoichiometric coefficient: 1.0

Reference/HMDB HMDB0000217
type: UnificationXref
id: HMDB0000217
db: HMDB

Reference/PubChem-compound 45038813
type: UnificationXref
id: 45038813
db: PubChem-compound

Reference/GENE ONTOLOGY GO 0005886
type: UnificationXref
id: GO:0005886
db: GENE ONTOLOGY

Compound/PW C001144 Endoplasmic Reticulum Membrane/Stoichiometry/1.0
type: Stoichiometry
physical entity: NADH
stoichiometric coefficient: 1.0

Compound/PW C009432 Mitochondrion/Stoichiometry/1.0
type: Stoichiometry
physical entity: Doxorubicin
stoichiometric coefficient: 1.0

TransportCatalysis159
type: Catalysis
controller: Canalicular multispecific organic anion transporter 1
controlled: Transport199
control type: ACTIVATION

TransportCatalysis158
type: Catalysis
controller: Multidrug resistance-associated protein 1
controlled: Transport199
control type: ACTIVATION

Doxorubicinol
type: SmallMolecule
cellular location: Cytoplasm
entity reference: Doxorubicinol

TransportCatalysis157
type: Catalysis
controller: Multidrug resistance protein 1
controlled: Transport199
control type: ACTIVATION

TransportCatalysis156
type: Catalysis
controller: Solute carrier family 22 member 16
controlled: Transport198
control type: ACTIVATION

Compound/PW C000721 Mitochondrial Inner Membrane/Stoichiometry/1.0
type: Stoichiometry
physical entity: NAD
stoichiometric coefficient: 1.0

Reference/KEGG Compound C00009
type: UnificationXref
id: C00009
db: KEGG Compound

NADH
type: SmallMolecule
cellular location: Endoplasmic Reticulum Membrane
entity reference: NADH

Reference/KEGG Compound C00008
type: UnificationXref
id: C00008
db: KEGG Compound

Reference/KEGG Compound C00006
type: UnificationXref
id: C00006
db: KEGG Compound

Doxorubicinol
type: SmallMoleculeReference
xref: Reference/PubChem-compound 83970
xref: Reference/CAS 54193-28-1
xref: Reference/HMDB HMDB0041884
xref: Reference/ChemSpider 75768
chemical formula: C27H31NO11
molecular weight: 545.1897
structure: ChemicalStructure/PW C022645

Reference/ChEBI CHEBI 18009
type: UnificationXref
id: CHEBI:18009
db: ChEBI

Reference/KEGG Compound C00001
type: UnificationXref
id: C00001
db: KEGG Compound

Reference/HMDB HMDB0001429
type: UnificationXref
id: HMDB0001429
db: HMDB

Compound/PW C000414 Cell Membrane/Stoichiometry/1.0
type: Stoichiometry
physical entity: Adenosine triphosphate
stoichiometric coefficient: 1.0

Reference/KEGG Compound C00005
type: UnificationXref
id: C00005
db: KEGG Compound

Reference/KEGG Compound C00004
type: UnificationXref
id: C00004
db: KEGG Compound

Reference/ChEBI CHEBI 18367
type: UnificationXref
id: CHEBI:18367
db: ChEBI

NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial
type: ProteinReference
xref: Reference/UniProt O75306
organism: BiologicalState10

Reference/KEGG Compound C00003
type: UnificationXref
id: C00003
db: KEGG Compound

Reference/ChemSpider 1032
type: UnificationXref
id: 1032
db: ChemSpider

NADP
type: SmallMolecule
cellular location: Cytoplasm
entity reference: NADP

Liver
type: TissueVocabulary
xref: Reference/BRENDA TISSUE ONTOLOGY BTO 0000759

Reference/KEGG Compound C00002
type: UnificationXref
id: C00002
db: KEGG Compound

ChemicalStructure/PW C000143
type: ChemicalStructure
structure format: SMILES

Aldo-keto reductase family 1 member C3
type: ProteinReference
xref: Reference/UniProt P42330
organism: Homo sapiens

Reference/HMDB HMDB0000221
type: UnificationXref
id: HMDB0000221
db: HMDB

Compound/PW C040618 Cytoplasm/Stoichiometry/1.0
type: Stoichiometry
physical entity: Doxorubicine hydroxyaglycone
stoichiometric coefficient: 1.0

ChemicalStructure/PW C000146
type: ChemicalStructure
structure format: SMILES

Mitochondrial Inner Membrane
type: CellularLocationVocabulary
xref: Reference/GENE ONTOLOGY GO 0005743

Reference/CAS 53-57-6
type: UnificationXref
id: 53-57-6
db: CAS

Compound/PW C040617 Cytoplasm/Stoichiometry/1.0
type: Stoichiometry
physical entity: Doxorubicinol deoxaglycone
stoichiometric coefficient: 1.0

NAD
type: SmallMoleculeReference
xref: Reference/ChEBI CHEBI 15846
xref: Reference/HMDB HMDB0000902
xref: Reference/CAS 53-84-9
xref: Reference/KEGG Compound C00003
xref: Reference/PubChem-compound 5893
xref: Reference/BioCyc NAD
xref: Reference/ChemSpider 5682
chemical formula: C21H27N7O14P2
molecular weight: 663.10913
structure: ChemicalStructure/PW C000721

ATP-binding cassette sub-family G member 2
type: Protein
entity reference: ATP-binding cassette sub-family G member 2

Reference/HMDB HMDB0000902
type: UnificationXref
id: HMDB0000902
db: HMDB

Extracellular Space
type: CellularLocationVocabulary
xref: Reference/GENE ONTOLOGY GO 0005615

Alcohol dehydrogenase [NADP(+)]
type: ProteinReference
xref: Reference/UniProt P14550
organism: Homo sapiens

Reference/UniProt P47989
type: UnificationXref
id: P47989
db: UniProt

NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial
type: Protein
cellular location: Mitochondrial Inner Membrane
entity reference: NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial

Reference/BioCyc NAD(P)
type: UnificationXref
id: NAD(P)
db: BioCyc

NADH
type: SmallMoleculeReference
xref: Reference/HMDB HMDB0001487
xref: Reference/CAS 58-68-4
xref: Reference/PubChem-compound 439153
xref: Reference/BioCyc NADH
xref: Reference/ChemSpider 388299
xref: Reference/KEGG Compound C00004
xref: Reference/ChEBI CHEBI 16908
chemical formula: C21H29N7O14P2
molecular weight: 665.12476
structure: ChemicalStructure/PW C001144

Aldo-keto reductase family 1 member C3
type: Protein
cellular location: Cytoplasm
entity reference: Aldo-keto reductase family 1 member C3

Reference/PubChem-compound 5957
type: UnificationXref
id: 5957
db: PubChem-compound

BiologicalState53
type: BioSource
cell type: Hepatocyte
xref: Reference/TAXONOMY 9606
name: Homo sapiens, Liver, Hepatocyte
tissue: Liver

Reference/GENE ONTOLOGY GO 0005743
type: UnificationXref
id: GO:0005743
db: GENE ONTOLOGY

Hepatocyte
type: CellVocabulary
xref: Reference/CELL TYPE ONTOLOGY CL 0000182

Reference/PubChem-compound 10476988
type: UnificationXref
id: 10476988
db: PubChem-compound

Doxorubicin
type: SmallMolecule
cellular location: Cytoplasm
entity reference: Doxorubicin

Solute carrier family 22 member 16
type: ProteinReference
xref: Reference/UniProt Q86VW1

Reference/CAS 56-65-5
type: UnificationXref
id: 56-65-5
db: CAS

Reference/CAS 53-84-9
type: UnificationXref
id: 53-84-9
db: CAS

Reference/UniProt P08183
type: UnificationXref
id: P08183
db: UniProt

1.14.13.39
type: BiochemicalReaction
participant stoichiometry: Compound/PW C001144 Mitochondrial Inner Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C040616 Cytoplasm/Stoichiometry/1.0
participant stoichiometry: Compound/PW C009432 Mitochondrial Inner Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C040616 Mitochondrial Inner Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C009432 Endoplasmic Reticulum Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C000721 Endoplasmic Reticulum Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C000721 Cytoplasm/Stoichiometry/1.0
participant stoichiometry: Compound/PW C001144 Endoplasmic Reticulum Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C001144 Cytoplasm/Stoichiometry/1.0
participant stoichiometry: Compound/PW C040616 Endoplasmic Reticulum Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C000721 Mitochondrial Inner Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C009432 Cytoplasm/Stoichiometry/1.0
right: Doxorubicin-semiquinone
right: NAD
spontaneous: false
EC number: 1.14.13.39
left: NADH
left: Doxorubicin
name: Doxorubicin + NADH → Doxorubicin-semiquinone + NAD
conversion direction: LEFT_TO_RIGHT

Reaction2035
type: BiochemicalReaction
participant stoichiometry: Compound/PW C040617 Cytoplasm/Stoichiometry/1.0
participant stoichiometry: Compound/PW C009432 Cytoplasm/Stoichiometry/1.0
right: Doxorubicinol deoxaglycone
spontaneous: false
left: Doxorubicin
name: Doxorubicin → Doxorubicinol deoxaglycone
conversion direction: LEFT_TO_RIGHT

Reaction2032
type: BiochemicalReaction
participant stoichiometry: Compound/PW C000146 Cytoplasm/Stoichiometry/1.0
participant stoichiometry: Compound/PW C022645 Cytoplasm/Stoichiometry/1.0
participant stoichiometry: Compound/PW C000143 Cytoplasm/Stoichiometry/1.0
participant stoichiometry: Compound/PW C009432 Cytoplasm/Stoichiometry/1.0
right: Doxorubicinol
right: NADP
spontaneous: false
left: Doxorubicin
left: NADPH
name: Doxorubicin + NADPH → Doxorubicinol + NADP
conversion direction: LEFT_TO_RIGHT

Reference/GENE ONTOLOGY GO 0005739
type: UnificationXref
id: GO:0005739
db: GENE ONTOLOGY

Compound/PW C009432 Endoplasmic Reticulum Membrane/Stoichiometry/1.0
type: Stoichiometry
physical entity: Doxorubicin
stoichiometric coefficient: 1.0

NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial
type: ProteinReference
xref: Reference/UniProt O75489
organism: BiologicalState10

Reference/GENE ONTOLOGY GO 0005615
type: UnificationXref
id: GO:0005615
db: GENE ONTOLOGY

Adenosine diphosphate
type: SmallMoleculeReference
xref: Reference/KEGG Compound C00008
xref: Reference/PubChem-compound 6022
xref: Reference/ChemSpider 5800
xref: Reference/CAS 58-64-0
xref: Reference/BioCyc ADP
xref: Reference/ChEBI CHEBI 16761
xref: Reference/HMDB HMDB0001341
chemical formula: C10H15N5O10P2
molecular weight: 427.02942
structure: ChemicalStructure/PW C001034

Reference/GENE ONTOLOGY GO 0005737
type: UnificationXref
id: GO:0005737
db: GENE ONTOLOGY

Reference/PathWhiz PW000626
type: UnificationXref
id: PW000626
db: PathWhiz

Doxorubicin
type: SmallMoleculeReference
xref: Reference/PubChem-compound 31703
xref: Reference/ChemSpider 29400
xref: Reference/CAS 23214-92-8
xref: Reference/ChEBI CHEBI 28748
xref: Reference/KEGG Compound C01661
xref: Reference/HMDB HMDB0015132
chemical formula: C27H29NO11
molecular weight: 543.1741
structure: ChemicalStructure/PW C009432

Reaction2036
type: BiochemicalReaction
participant stoichiometry: Compound/PW C040618 Cytoplasm/Stoichiometry/1.0
participant stoichiometry: Compound/PW C009432 Cytoplasm/Stoichiometry/1.0
right: Doxorubicine hydroxyaglycone
spontaneous: false
left: Doxorubicin
name: Doxorubicin → Doxorubicine hydroxyaglycone
conversion direction: LEFT_TO_RIGHT

Reaction2037
type: BiochemicalReaction
participant stoichiometry: Compound/PW C040618 Cytoplasm/Stoichiometry/1.0
participant stoichiometry: Compound/PW C040619 Cytoplasm/Stoichiometry/1.0
right: Doxorubicinol hydroxyaglycone
spontaneous: false
left: Doxorubicine hydroxyaglycone
name: Doxorubicine hydroxyaglycone → Doxorubicinol hydroxyaglycone
conversion direction: LEFT_TO_RIGHT

Transport198
type: Transport
participant stoichiometry: Compound/PW C009432 Extracellular Space/Stoichiometry/1.0
participant stoichiometry: Compound/PW C009432 Cytoplasm/Stoichiometry/1.0
right: Doxorubicin
spontaneous: false
left: Doxorubicin
name: Doxorubicin (→) Transport: Homo sapiens, Extracellular Space to Homo sapiens, Cell, Cytoplasm
conversion direction: LEFT_TO_RIGHT

Transport199
type: Transport
participant stoichiometry: Compound/PW C009432 Extracellular Space/Stoichiometry/1.0
participant stoichiometry: Compound/PW C009432 Cytoplasm/Stoichiometry/1.0
right: Doxorubicin
spontaneous: false
left: Doxorubicin
name: Doxorubicin (→) Transport: Homo sapiens, Cell, Cytoplasm to Homo sapiens, Extracellular Space
conversion direction: LEFT_TO_RIGHT

Endoplasmic Reticulum Membrane
type: CellularLocationVocabulary
xref: Reference/GENE ONTOLOGY GO 0005789

NADH
type: SmallMolecule
cellular location: Cytoplasm
entity reference: NADH

ChemicalStructure/PW C000721
type: ChemicalStructure
structure format: SMILES

Reference/BioCyc CPD-8587
type: UnificationXref
id: CPD-8587
db: BioCyc

Multidrug resistance-associated protein 1
type: Protein
entity reference: Multidrug resistance-associated protein 1

Compound/PW C009432 Cytoplasm/Stoichiometry/1.0
type: Stoichiometry
physical entity: Doxorubicin
stoichiometric coefficient: 1.0

Reference/ChemSpider 5682
type: UnificationXref
id: 5682
db: ChemSpider

ChemicalStructure/PW C001144
type: ChemicalStructure
structure format: SMILES

Nitric-oxide synthase, endothelial
type: Complex
component stoichiometry: Protein/872 Cytoplasm/Stoichiometry/2.0
cellular location: Cytoplasm
component: Nitric oxide synthase, endothelial

Adenosine triphosphate
type: SmallMolecule
cellular location: Cell Membrane
entity reference: Adenosine triphosphate

Reference/ChemSpider 75768
type: UnificationXref
id: 75768
db: ChemSpider

Reference/HMDB HMDB0001341
type: UnificationXref
id: HMDB0001341
db: HMDB

Carbonyl reductase [NADPH] 3
type: ProteinReference
xref: Reference/UniProt O75828
organism: Homo sapiens

Reference/CAS 23214-92-8
type: UnificationXref
id: 23214-92-8
db: CAS

Carbonyl reductase [NADPH] 1
type: ProteinReference
xref: Reference/UniProt P16152
organism: Homo sapiens

Canalicular multispecific organic anion transporter 1
type: Protein
entity reference: Canalicular multispecific organic anion transporter 1

Reference/ChemSpider 5675
type: UnificationXref
id: 5675
db: ChemSpider

RalA-binding protein 1
type: Protein
entity reference: RalA-binding protein 1

Water
type: SmallMolecule
cellular location: Cell Membrane
entity reference: Water

NAD(P)H dehydrogenase [quinone] 1
type: Protein
cellular location: Cytoplasm
entity reference: NAD(P)H dehydrogenase [quinone] 1

ChemicalStructure/PW C001034
type: ChemicalStructure
structure format: SMILES

ReactionCoupledTransport74
type: TransportWithBiochemicalReaction
participant stoichiometry: Compound/PW C001104 Cell Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C000414 Cell Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C001034 Cell Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C009432 Cell Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C001420 Cell Membrane/Stoichiometry/1.0
right: Phosphate
right: Adenosine diphosphate
right: Doxorubicin
spontaneous: false
left: Doxorubicin
left: Water
left: Adenosine triphosphate
name: Adenosine triphosphate + Doxorubicin + Water → Adenosine diphosphate + Doxorubicin + Phosphate
conversion direction: LEFT_TO_RIGHT

ReactionCoupledTransport73
type: TransportWithBiochemicalReaction
participant stoichiometry: Compound/PW C001104 Cell Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C000414 Cell Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C001034 Cell Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C009432 Cell Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C001420 Cell Membrane/Stoichiometry/1.0
right: Phosphate
right: Adenosine diphosphate
right: Doxorubicin
spontaneous: false
left: Doxorubicin
left: Water
left: Adenosine triphosphate
name: Adenosine triphosphate + Doxorubicin + Water → Adenosine diphosphate + Doxorubicin + Phosphate
conversion direction: LEFT_TO_RIGHT

Compound/PW C040616 Mitochondrial Inner Membrane/Stoichiometry/1.0
type: Stoichiometry
physical entity: Doxorubicin-semiquinone
stoichiometric coefficient: 1.0

Multidrug resistance protein 1
type: Protein
cellular location: Cell Membrane
entity reference: Multidrug resistance protein 1

Protein/176 Cytoplasm/Stoichiometry/2.0
type: Stoichiometry
physical entity: Xanthine dehydrogenase/oxidase
stoichiometric coefficient: 2.0

NAD
type: SmallMolecule
cellular location: Endoplasmic Reticulum Membrane
entity reference: NAD

Reference/CAS 54193-28-1
type: UnificationXref
id: 54193-28-1
db: CAS

Cytoplasm
type: CellularLocationVocabulary
xref: Reference/GENE ONTOLOGY GO 0005737

Compound/PW C001144 Cytoplasm/Stoichiometry/1.0
type: Stoichiometry
physical entity: NADH
stoichiometric coefficient: 1.0

ChemicalStructure/PW C009432
type: ChemicalStructure
structure format: SMILES

NADPH
type: SmallMolecule
cellular location: Cytoplasm
entity reference: NADPH

ReactionCoupledTransport72
type: TransportWithBiochemicalReaction
participant stoichiometry: Compound/PW C001104 Cell Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C000414 Cell Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C001034 Cell Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C009432 Cell Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C001420 Cell Membrane/Stoichiometry/1.0
right: Phosphate
right: Adenosine diphosphate
right: Doxorubicin
spontaneous: false
left: Doxorubicin
left: Water
left: Adenosine triphosphate
name: Adenosine triphosphate + Doxorubicin + Water → Adenosine diphosphate + Doxorubicin + Phosphate
conversion direction: LEFT_TO_RIGHT

3.6.3.44
type: TransportWithBiochemicalReaction
participant stoichiometry: Compound/PW C001104 Cell Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C000414 Cell Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C001034 Cell Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C009432 Cell Membrane/Stoichiometry/1.0
participant stoichiometry: Compound/PW C001420 Cell Membrane/Stoichiometry/1.0
right: Phosphate
right: Adenosine diphosphate
right: Doxorubicin
spontaneous: false
EC number: 3.6.3.44
left: Doxorubicin
left: Water
left: Adenosine triphosphate
name: Adenosine triphosphate + Doxorubicin + Water → Adenosine diphosphate + Doxorubicin + Phosphate
conversion direction: LEFT_TO_RIGHT

Reference/ChEBI CHEBI 15422
type: UnificationXref
id: CHEBI:15422
db: ChEBI

Nitric oxide synthase, endothelial
type: Protein
cellular location: Cytoplasm
entity reference: Nitric oxide synthase, endothelial

Compound/PW C022645 Cytoplasm/Stoichiometry/1.0
type: Stoichiometry
physical entity: Doxorubicinol
stoichiometric coefficient: 1.0

Homo sapiens
type: BioSource
xref: Reference/TAXONOMY 9606

Multidrug resistance protein 1
type: Protein
entity reference: Multidrug resistance protein 1

Reference/ChemSpider 388299
type: UnificationXref
id: 388299
db: ChemSpider

Reference/CAS 7732-18-5
type: UnificationXref
id: 7732-18-5
db: CAS

NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial
type: Protein
cellular location: Endoplasmic Reticulum Membrane
entity reference: NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial

Reference/UniProt O75489
type: UnificationXref
id: O75489
db: UniProt

Reference/HMDB HMDB0001487
type: UnificationXref
id: HMDB0001487
db: HMDB

Reference/UniProt P16435
type: UnificationXref
id: P16435
db: UniProt

Reference/GENE ONTOLOGY GO 0005789
type: UnificationXref
id: GO:0005789
db: GENE ONTOLOGY

Reference/ChEBI CHEBI 28748
type: UnificationXref
id: CHEBI:28748
db: ChEBI

Doxorubicin
type: SmallMolecule
cellular location: Mitochondrial Inner Membrane
entity reference: Doxorubicin

Xanthine dehydrogenase/oxidase
type: Complex
component stoichiometry: Protein/176 Cytoplasm/Stoichiometry/2.0
cellular location: Cytoplasm
component: Xanthine dehydrogenase/oxidase

ATP-binding cassette sub-family G member 2
type: ProteinReference
xref: Reference/UniProt Q9UNQ0

Adenosine triphosphate
type: SmallMoleculeReference
xref: Reference/ChEBI CHEBI 15422
xref: Reference/PubChem-compound 5957
xref: Reference/HMDB HMDB0000538
xref: Reference/CAS 56-65-5
xref: Reference/ChemSpider 5742
xref: Reference/BioCyc ATP
xref: Reference/KEGG Compound C00002
chemical formula: C10H16N5O13P3
molecular weight: 506.99576
structure: ChemicalStructure/PW C000414

Reference/PubChem-compound 83970
type: UnificationXref
id: 83970
db: PubChem-compound

BiologicalState10
type: BioSource
xref: Reference/TAXONOMY 9606
name: Homo sapiens, Liver
tissue: Liver

Reference/ChEBI CHEBI 16761
type: UnificationXref
id: CHEBI:16761
db: ChEBI

Doxorubicin-semiquinone
type: SmallMolecule
cellular location: Endoplasmic Reticulum Membrane
entity reference: Doxorubicin-semiquinone

Reaction2073
type: BiochemicalReaction
participant stoichiometry: Compound/PW C040616 Cytoplasm/Stoichiometry/1.0
participant stoichiometry: Compound/PW C009432 Cytoplasm/Stoichiometry/1.0
right: Doxorubicin
spontaneous: false
left: Doxorubicin-semiquinone
name: Doxorubicin-semiquinone → Doxorubicin
conversion direction: LEFT_TO_RIGHT

Doxorubicinol hydroxyaglycone
type: SmallMolecule
cellular location: Cytoplasm
entity reference: Doxorubicinol hydroxyaglycone

Reference/TAXONOMY 9606
type: UnificationXref
id: 9606
db: TAXONOMY

Reference/PubChem-compound 962
type: UnificationXref
id: 962
db: PubChem-compound

Compound/PW C000721 Endoplasmic Reticulum Membrane/Stoichiometry/1.0
type: Stoichiometry
physical entity: NAD
stoichiometric coefficient: 1.0

Canalicular multispecific organic anion transporter 1
type: Protein
cellular location: Cell Membrane
entity reference: Canalicular multispecific organic anion transporter 1

Reference/UniProt O75828
type: UnificationXref
id: O75828
db: UniProt

Reference/ChemSpider 5800
type: UnificationXref
id: 5800
db: ChemSpider

ReactionCatalysis1915
type: Catalysis
controller: NAD(P)H dehydrogenase [quinone] 1
controlled: Reaction2035
control type: ACTIVATION

ReactionCatalysis1914
type: Catalysis
controller: Xanthine dehydrogenase/oxidase
controlled: Reaction2035
control type: ACTIVATION

ReactionCatalysis1916
type: Catalysis
controller: NADPH--cytochrome P450 reductase
controlled: Reaction2035
control type: ACTIVATION

Reference/PubChem-compound 5893
type: UnificationXref
id: 5893
db: PubChem-compound

Compound/PW C009432 Mitochondrial Inner Membrane/Stoichiometry/1.0
type: Stoichiometry
physical entity: Doxorubicin
stoichiometric coefficient: 1.0

Reference/UniProt P14550
type: UnificationXref
id: P14550
db: UniProt

Reference/PubChem-compound 72401
type: UnificationXref
id: 72401
db: PubChem-compound

Reference/HMDB HMDB0002111
type: UnificationXref
id: HMDB0002111
db: HMDB

Cell Membrane
type: CellularLocationVocabulary
xref: Reference/GENE ONTOLOGY GO 0005886

Reference/ChEBI CHEBI 15377
type: UnificationXref
id: CHEBI:15377
db: ChEBI

Doxorubicinol deoxaglycone
type: SmallMolecule
cellular location: Cytoplasm
entity reference: Doxorubicinol deoxaglycone

Multidrug resistance-associated protein 1
type: ProteinReference
xref: Reference/UniProt P33527

NAD(P)H dehydrogenase [quinone] 1
type: Complex
component stoichiometry: Protein/1543 Cytoplasm/Stoichiometry/2.0
cellular location: Cytoplasm
component: NAD(P)H dehydrogenase [quinone] 1

Reference/CAS 14265-44-2
type: UnificationXref
id: 14265-44-2
db: CAS

Reference/CAS 58-64-0
type: UnificationXref
id: 58-64-0
db: CAS

ChemicalStructure/PW C000414
type: ChemicalStructure
structure format: SMILES

Reference/PubChem-compound 5886
type: UnificationXref
id: 5886
db: PubChem-compound

Nitric oxide synthase, endothelial
type: ProteinReference
xref: Reference/UniProt P29474
organism: Homo sapiens

Reference/UniProt O75251
type: UnificationXref
id: O75251
db: UniProt

Alcohol dehydrogenase [NADP(+)]
type: Protein
cellular location: Cytoplasm
entity reference: Alcohol dehydrogenase [NADP(+)]

Reference/HMDB HMDB0061206
type: UnificationXref
id: HMDB0061206
db: HMDB

Transport202
type: Transport
participant stoichiometry: Compound/PW C040616 Cytoplasm/Stoichiometry/1.0
participant stoichiometry: Compound/PW C040616 Mitochondrion/Stoichiometry/1.0
right: Doxorubicin-semiquinone
spontaneous: false
left: Doxorubicin-semiquinone
name: Doxorubicin-semiquinone (↔) Transport: Homo sapiens, Cell, Mitochondrion to Homo sapiens, Cell, Cytoplasm
conversion direction: LEFT_TO_RIGHT

Transport201
type: Transport
participant stoichiometry: Compound/PW C009432 Mitochondrion/Stoichiometry/1.0
participant stoichiometry: Compound/PW C009432 Cytoplasm/Stoichiometry/1.0
right: Doxorubicin
spontaneous: false
left: Doxorubicin
name: Doxorubicin (↔) Transport: Homo sapiens, Cell, Cytoplasm to Homo sapiens, Cell, Mitochondrion
conversion direction: LEFT_TO_RIGHT

NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial
type: Protein
cellular location: Mitochondrial Inner Membrane
entity reference: NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial

Reference/ChemSpider 29400
type: UnificationXref
id: 29400
db: ChemSpider

Reference/ChemSpider 23935799
type: UnificationXref
id: 23935799
db: ChemSpider

RalA-binding protein 1
type: ProteinReference
xref: Reference/UniProt Q15311

Compound/PW C000721 Cytoplasm/Stoichiometry/1.0
type: Stoichiometry
physical entity: NAD
stoichiometric coefficient: 1.0

Canalicular multispecific organic anion transporter 1
type: ProteinReference
xref: Reference/UniProt Q92887

Doxorubicin Metabolism Pathway
type: Pathway
pathway order: PathwayEnzymeReaction/3672
pathway order: PathwayEnzymeReaction/3670
pathway order: PathwayEnzymeReaction/3671
pathway order: PathwayEnzymeReaction/2635
pathway order: PathwayEnzymeReaction/3669
pathway order: PathwayEnzymeReaction/2631
pathway order: PathwayEnzymeReaction/2632
pathway order: PathwayTransport/2704
pathway order: PathwayEnzymeReaction/2633
pathway order: PathwayEnzymeReaction/3667
pathway order: PathwayEnzymeReaction/2634
pathway order: PathwayTransport/2702
pathway order: PathwayEnzymeReaction/3668
pathway order: PathwayTransport/2707
pathway order: PathwayTransport/2708
pathway order: PathwayTransport/2705
pathway order: PathwayTransport/2706
pathway order: PathwayEnzymeReaction/2718
pathway order: PathwayTransport/2611
pathway order: PathwayEnzymeReaction/2624
pathway order: PathwayEnzymeReaction/3658
pathway order: PathwayEnzymeReaction/2625
pathway order: PathwayEnzymeReaction/3659
pathway order: PathwayEnzymeReaction/2626
pathway order: PathwayTransport/2697
pathway order: PathwayEnzymeReaction/2703
pathway order: PathwayEnzymeReaction/2627
pathway order: PathwayEnzymeReaction/2721
pathway order: PathwayEnzymeReaction/3656
pathway order: PathwayEnzymeReaction/2722
pathway order: PathwayEnzymeReaction/3657
pathway component: Transport198
pathway component: Transport199
pathway component: TransportCatalysis161
pathway component: TransportCatalysis160
pathway component: ReactionCatalysis1915
pathway component: ReactionCatalysis1914
pathway component: ReactionCatalysis1916
pathway component: ReactionCatalysis1902
pathway component: ReactionCatalysis1901
pathway component: TransportCatalysis159
pathway component: TransportCatalysis158
pathway component: TransportCatalysis157
pathway component: TransportCatalysis156
pathway component: ReactionCatalysis1904
pathway component: ReactionCatalysis1903
pathway component: ReactionCatalysis1906
pathway component: ReactionCatalysis1908
pathway component: ReactionCatalysis1907
pathway component: ReactionCatalysis1909
pathway component: 1.14.13.39
pathway component: ReactionCoupledTransport74
pathway component: Reaction2035
pathway component: ReactionCoupledTransport73
pathway component: Reaction2032
pathway component: ReactionCatalysis1913
pathway component: Reaction2073
pathway component: ReactionCatalysis1912
pathway component: Transport202
pathway component: ReactionCoupledTransportCatalysis87
pathway component: Transport201
pathway component: ReactionCoupledTransportCatalysis86
pathway component: Reaction2036
pathway component: ReactionCoupledTransport72
pathway component: ReactionCoupledTransportCatalysis89
pathway component: Reaction2037
pathway component: 3.6.3.44
pathway component: ReactionCoupledTransportCatalysis88
xref: Reference/PathWhiz PW000626
xref: Reference/SMPDB SMP0000650
organism: Homo sapiens

Reference/PubChem-compound 22833512
type: UnificationXref
id: 22833512
db: PubChem-compound

Reference/UniProt P42330
type: UnificationXref
id: P42330
db: UniProt

Water
type: SmallMoleculeReference
xref: Reference/PubChem-compound 962
xref: Reference/ChEBI CHEBI 15377
xref: Reference/KEGG Compound C00001
xref: Reference/ChemSpider 937
xref: Reference/HMDB HMDB0002111
xref: Reference/CAS 7732-18-5
chemical formula: H2O
molecular weight: 18.010565
structure: ChemicalStructure/PW C001420

Carbonyl reductase [NADPH] 3
type: Protein
cellular location: Cytoplasm
entity reference: Carbonyl reductase [NADPH] 3

Reference/BioCyc NADH
type: UnificationXref
id: NADH
db: BioCyc

Xanthine dehydrogenase/oxidase
type: Protein
cellular location: Cytoplasm
entity reference: Xanthine dehydrogenase/oxidase

Doxorubicine hydroxyaglycone
type: SmallMolecule
cellular location: Cytoplasm
entity reference: Doxorubicine hydroxyaglycone

Reference/BioCyc NAD
type: UnificationXref
id: NAD
db: BioCyc

Reference/PubChem-compound 1061
type: UnificationXref
id: 1061
db: PubChem-compound

Reference/UniProt Q9UNQ0
type: UnificationXref
id: Q9UNQ0
db: UniProt

NAD(P)H dehydrogenase [quinone] 1
type: ProteinReference
xref: Reference/UniProt P15559
organism: Homo sapiens

Multidrug resistance protein 1
type: ProteinReference
xref: Reference/UniProt P08183

ChemicalStructure/PW C040617
type: ChemicalStructure
structure format: SMILES

ChemicalStructure/PW C040616
type: ChemicalStructure
structure format: SMILES

ChemicalStructure/PW C022645
type: ChemicalStructure
structure format: SMILES

Reference/UniProt P15559
type: UnificationXref
id: P15559
db: UniProt

Reference/UniProt P33527
type: UnificationXref
id: P33527
db: UniProt

ChemicalStructure/PW C040619
type: ChemicalStructure
structure format: SMILES

ChemicalStructure/PW C040618
type: ChemicalStructure
structure format: SMILES

Adenosine diphosphate
type: SmallMolecule
cellular location: Cell Membrane
entity reference: Adenosine diphosphate

Compound/PW C040616 Mitochondrion/Stoichiometry/1.0
type: Stoichiometry
physical entity: Doxorubicin-semiquinone
stoichiometric coefficient: 1.0

Doxorubicin
type: SmallMolecule
cellular location: Cell Membrane
entity reference: Doxorubicin

Doxorubicin
type: SmallMolecule
cellular location: Extracellular Space
entity reference: Doxorubicin

NAD
type: SmallMolecule
cellular location: Cytoplasm
entity reference: NAD