Hemesynthesis defects and porphyrias (WP5169)

Homo sapiens

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Defects in the heme biosynthesis in a hepatocyte can result in specific metabolic disorders called porphyrias. These diseases can be split into two categories, namely acute porphyrias and non-acute porphyrias. Acute hepatic porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), and Doss porphyria (ALADP) are all part of the acute-hepatic porphyrias. This type is often associated with an overproduction of neurotoxic porphyrins and porphyrin precursors. The non-acute porphyrias include, porphyria cutanea tarda, erythropoietic porphyria, and congenital erythropoietic porphyria. These diseases are instead characterised by photosensitivity of the skin and in severe cases liver damage, caused by porphyrins. Another type of porphyria are the X-linked protoporphyria diseases, which are a result of a gain of function mutation in the 5-aminolevulinic acid synthase 2 gene. This causes an accumulation of protoporphyrin IX. The disease present in the patient is determined by what enzyme is affected in the heme biosynthesis pathway. This pathway has been constructed using chapter 33 of the book; Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases (first edition), by N.Blau et al (ISBN 3642403360 (978-3642403361)).

Authors

Julia Johnsson , Denise Slenter , and Eric Weitz

Activity

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Organisms

Homo sapiens

Communities

Inherited Metabolic Disorders (IMD) Pathways Rare Diseases

Annotations

Disease Ontology

sideroblastic anemia 1 acute porphyria erythropoietic protoporphyria inherited metabolic disorder cutaneous porphyria porphyria cutanea tarda porphyria hepatoerythropoietic porphyria acute intermittent porphyria

Pathway Ontology

inborn error of metabolism pathway erythropoietic porphyria pathway pathway porphyria pathway acute intermittent porphyria pathway hepatic porphyria pathway disease pathway heme biosynthetic pathway

Cell Type Ontology

hepatocyte

Participants
Query Drugst.One

Label Type Compact URI Comment
Pentacarboxyl porphyrinogen III Metabolite hmdb:HMDB0001957 Alternative name: Pentacarboxyporphyrinogen III
Protoporphyrin IX Metabolite chebi:57306
Uroporphyrinogen III Metabolite chebi:15437
Coproporphyrinogen I Metabolite chebi:28607
Protoporphyrinogen IX Metabolite chebi:15435
Protoheme Metabolite chebi:26355 Alternative name: Heme
delta-aminolevulinic acid Metabolite chebi:17549
Glycine Metabolite hmdb:HMDB0000123 Alternative name: Glycine
Porphobilinogen Metabolite chebi:17381
hydroxymethylbilane Metabolite chebi:57845
Uroporphyrinogen I Metabolite chebi:28766
succinyl-CoA Metabolite chebi:15380
Heptacarboxylporphyrin III Metabolite hmdb:HMDB0001956 Alternative name: Heptacarboxyporphyrinogen III
Pentacarboxylporphyrin I Metabolite hmdb:HMDB0000789 Alternative name: Pentacarboxyporphyrinogen I
Hexacarboxylporphyrin III Metabolite hmdb:HMDB0001952 Alternative name: Hexacarboxyporphyrinogen III
Hexacarboxylporphyrin I Metabolite hmdb:HMDB0000743 Alternative name: Hexacarboxyporphyrinogen I
Heptaporphyrin Metabolite chebi:89912 Alternative name: Heptacarboxyporphyrinogen I
Coproporphyrinogen III Metabolite chebi:15439
PPOX GeneProduct ncbigene:5498 Alternative name:Proto-Oxidase
HMBS GeneProduct ncbigene:3145 Alternative name: PBG-Deaminase
ALAS1 GeneProduct ncbigene:211 Alternative name: ALA-Synthase
ALAD GeneProduct ncbigene:210 Alternative name: ALA-Dehydratase
ALAS2 GeneProduct ncbigene:212 Alternative name: ALA-Synthase
UROS GeneProduct ncbigene:7390 Alternative name: UR0-111-synthase
UROD GeneProduct ncbigene:7389 Alternative name: URO-Decarboxylase
CPOX GeneProduct ncbigene:1371 Alternative name: Copro-Oxidase
FECH GeneProduct ncbigene:2235 Alternative name: Ferrocnelatase

References

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