UROS
label: UniProt:P10746 UROS

GNT1
label: UGT1
label: UGT1A1
label: UniProt:P22309 UGT1A1

COX10
label: UniProt:Q12887 COX10

COX15
label: UniProt:Q7KZN9 COX15

The heme ring is cleaved by heme oxygenase
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005789
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005789
type: GO_0004392
BFO_0000050: Heme degradation
directly activates: Biliverdin is reduced to bilirubin
directly activates: Catalysis2980

ALAS condenses SUCC-CoA and Gly to form dALA
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005759
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005759
type: GO_0003870
BFO_0000050: Heme biosynthesis
directly activates: ALA is transported from the mitochondrial matrix to the cytosol
label: Succinyl CoA and glycine condense to form 5-aminolevulinate (ALA)

ALA is transported from the mitochondrial matrix to the cytosol
type: GO_0003674
BFO_0000050: Heme biosynthesis
directly activates: ALAD condenses 2 dALAs to form PBG
directly activates: Catalysis2970
label: Mitochondrial dALA translocates to cytosol

ALAD binds to Pb2+
type: GO_0003674
BFO_0000050: Heme biosynthesis
label: ALAD octamer associates with Pb++, forming a catalytically inactive complex

ALAD condenses 2 dALAs to form PBG
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0004655
BFO_0000050: Heme biosynthesis
directly activates: 4 PBGs bind to form HMB
directly activates: Catalysis2971
label: Two molecules of ALA condense to form porphobilinogen (PBG)

4 PBGs bind to form HMB
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0004418
BFO_0000050: Heme biosynthesis
directly activates: Conversion of HMB to uroporphyrinogen III
directly activates: HMBL spontaneously transforms to URO1
directly activates: Catalysis2972
label: Four PBGs combine through deamination to form hydroxymethylbilane (HMB)

Conversion of HMB to uroporphyrinogen III
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: enabled by
  some values from: UROS
type: Restriction
  on property: enabled by
  some values from: UROS
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0004852
BFO_0000050: Heme biosynthesis
directly activates: UROD decarboxylates URO3 to COPRO3
directly activates: Catalysis2973
label: UROS transforms HMB to URO3

HMBL spontaneously transforms to URO1
type: GO_0003674
BFO_0000050: Heme biosynthesis
directly activates: UROD decarboxylates URO1 to COPRO1
directly activates: Catalysis2974
label: Spontaneous conversion of HMBL to uroporphyrinogen I (URO1)

UROD decarboxylates URO3 to COPRO3
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0004853
BFO_0000050: Heme biosynthesis
directly activates: Cytosolic COPRO3 translocates to mitochondrial intermembrane space
label: Uroporphyrinogen III is decarboxylated to form coproporphyrinogen III

UROD decarboxylates URO1 to COPRO1
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0004853
BFO_0000050: Heme biosynthesis
label: Uroporphyrinogen I is decarboxylated to form coproporphyrinogen I

Cytosolic COPRO3 translocates to mitochondrial intermembrane space
type: GO_0003674
BFO_0000050: Heme biosynthesis
directly activates: CPO transforms COPRO3 to PPGEN9
directly activates: Catalysis2975
label: Translocation of coproporphyrinogen III from the cytosol to the mitochondrial intermembrane space

CPO transforms COPRO3 to PPGEN9
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005758
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005758
type: GO_0004109
BFO_0000050: Heme biosynthesis
directly activates: Oxidation of protoporphyrinogen IX to protoporphyrin IX
directly activates: Catalysis2976
label: Conversion of coproporphyrinogen III to protoporphyrinogen IX

Oxidation of protoporphyrinogen IX to protoporphyrin IX
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005758
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005758
type: GO_0004729
BFO_0000050: Heme biosynthesis
directly activates: Mitochondrial intermembrane PRIN9 translocates to mitochondrial matrix
label: PPO oxidises PPGEN9 to PRIN9

Mitochondrial intermembrane PRIN9 translocates to mitochondrial matrix
type: GO_0003674
BFO_0000050: Heme biosynthesis
directly activates: FECH binds Fe2+ to PRIN9 to form heme
directly activates: Catalysis2977
directly activates: Control488
label: Protoporphyrin IX is transported from the mitochondrial intermembrane space into the mitochondrial matrix

FECH binds Fe2+ to PRIN9 to form heme
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005759
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005759
type: GO_0004325
BFO_0000050: Heme biosynthesis
directly activates: COX10 transforms heme to heme O
directly activates: Catalysis2978
label: Ferrous iron is inserted into protoporphyrin IX to form heme

COX10 transforms heme to heme O
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005743
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005743
type: Restriction
  on property: enabled by
  some values from: COX10
type: Restriction
  on property: enabled by
  some values from: COX10
type: GO_0008495
BFO_0000050: Heme biosynthesis
directly activates: COX15 transforms heme O to heme A
directly activates: Catalysis2979

COX15 transforms heme O to heme A
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005743
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005743
type: Restriction
  on property: enabled by
  some values from: COX15
type: Restriction
  on property: enabled by
  some values from: COX15
type: GO_0016627
BFO_0000050: Heme biosynthesis

Biliverdin is reduced to bilirubin
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005829
type: GO_0004074
BFO_0000050: Heme degradation
directly activates: Bilirubin translocates from the cytosol to the ER lumen

Bilirubin translocates from the cytosol to the ER lumen
type: GO_0003674
BFO_0000050: Heme degradation
directly activates: Bilirubin forms a monoglucuronide
directly activates: Catalysis2981

Bilirubin forms a monoglucuronide
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005789
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005789
type: Restriction
  on property: enabled by
  some values from: GNT1
type: Restriction
  on property: enabled by
  some values from: GNT1
type: GO_0006789
type: GO_0015020
BFO_0000050: Heme degradation
directly activates: Bilirubin monoglucuronide is conjugated to bilirubin diglucuronide
directly activates: Catalysis2982
label: bilirubin + UDP-glucuronic acid => bilirubin monoglucuronide + UDP

Bilirubin monoglucuronide is conjugated to bilirubin diglucuronide
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005789
type: Restriction
  on property: BFO_0000066
  some values from: GO_0005789
type: GO_0015020
BFO_0000050: Heme degradation
label: bilirubin monoglucuronide + UDP-glucuronic acid => bilirubin diglucuronide + UDP

Metabolism of porphyrins
type: GO_0008150
label: Porphyrin metabolism

Heme biosynthesis
type: GO_0008150
BFO_0000050: Metabolism of porphyrins

Heme degradation
type: GO_0008150
BFO_0000050: Metabolism of porphyrins