Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to uroporphyria:
Hepatic uroporphyria is a disorder where the disturbance of heme biosynthesis results in accumulation and excretion of uroporphyrin, heptacarboxyl- and hexacarboxyl porphyrin: collectively referred to as highly carboxylated porphyrins (HCPs). The disorder is due to a homozygous mutation in uroporphy...
Gespeichert in:
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| Weitere Verfasser: | , , |
| Format: | Elektronisch E-Book |
| Sprache: | English |
| Veröffentlicht: |
Paris
OECD Publishing
2019
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| Schriftenreihe: | OECD Series on Adverse Outcome Pathways
no.15 |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Zusammenfassung: | Hepatic uroporphyria is a disorder where the disturbance of heme biosynthesis results in accumulation and excretion of uroporphyrin, heptacarboxyl- and hexacarboxyl porphyrin: collectively referred to as highly carboxylated porphyrins (HCPs). The disorder is due to a homozygous mutation in uroporphyrinogen decarboxylase (UROD), an enzyme involved in the heme biosynthesis pathway, or may be chemically induced, which involves the inhibition of UROD. This AOP describes the linkages leading to chemically induced porphyria through the activation of the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor. AHR activation leads to the induction of cytochrome P450 1A2, a phase I metabolising enzyme, which in turn results in excessive oxidation of uroporphyrinogen. This oxidation produces a UROD inhibitor, preventing the conversion of uroporphyrinogen to coprouroporphyrinogen and increasing the synthesis of the UROD inhibitor in a positive feedback loop. The accumulation of uroporphyrinogen leads to its preferential oxidation and accumulation of HCP in various organs (Uroporphyria). |
| Beschreibung: | 1 Online-Ressource (78 p.) |
| DOI: | 10.1787/fde13d2c-en |
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| 520 | |a Hepatic uroporphyria is a disorder where the disturbance of heme biosynthesis results in accumulation and excretion of uroporphyrin, heptacarboxyl- and hexacarboxyl porphyrin: collectively referred to as highly carboxylated porphyrins (HCPs). The disorder is due to a homozygous mutation in uroporphyrinogen decarboxylase (UROD), an enzyme involved in the heme biosynthesis pathway, or may be chemically induced, which involves the inhibition of UROD. This AOP describes the linkages leading to chemically induced porphyria through the activation of the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor. AHR activation leads to the induction of cytochrome P450 1A2, a phase I metabolising enzyme, which in turn results in excessive oxidation of uroporphyrinogen. This oxidation produces a UROD inhibitor, preventing the conversion of uroporphyrinogen to coprouroporphyrinogen and increasing the synthesis of the UROD inhibitor in a positive feedback loop. The accumulation of uroporphyrinogen leads to its preferential oxidation and accumulation of HCP in various organs (Uroporphyria). | ||
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| spelling | Farhat, Amani VerfasserIn aut Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to uroporphyria Amani, Farhat ... [et al] Paris OECD Publishing 2019 1 Online-Ressource (78 p.) Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier OECD Series on Adverse Outcome Pathways no.15 Hepatic uroporphyria is a disorder where the disturbance of heme biosynthesis results in accumulation and excretion of uroporphyrin, heptacarboxyl- and hexacarboxyl porphyrin: collectively referred to as highly carboxylated porphyrins (HCPs). The disorder is due to a homozygous mutation in uroporphyrinogen decarboxylase (UROD), an enzyme involved in the heme biosynthesis pathway, or may be chemically induced, which involves the inhibition of UROD. This AOP describes the linkages leading to chemically induced porphyria through the activation of the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor. AHR activation leads to the induction of cytochrome P450 1A2, a phase I metabolising enzyme, which in turn results in excessive oxidation of uroporphyrinogen. This oxidation produces a UROD inhibitor, preventing the conversion of uroporphyrinogen to coprouroporphyrinogen and increasing the synthesis of the UROD inhibitor in a positive feedback loop. The accumulation of uroporphyrinogen leads to its preferential oxidation and accumulation of HCP in various organs (Uroporphyria). Environment Social Issues/Migration/Health Manning, Gillian MitwirkendeR ctb O'Brien, Jason MitwirkendeR ctb Kennedy, Sean W... MitwirkendeR ctb FWS01 ZDB-13-SOC FWS_PDA_SOC https://doi.org/10.1787/fde13d2c-en Volltext |
| spellingShingle | Farhat, Amani Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to uroporphyria Environment Social Issues/Migration/Health |
| title | Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to uroporphyria |
| title_auth | Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to uroporphyria |
| title_exact_search | Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to uroporphyria |
| title_full | Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to uroporphyria Amani, Farhat ... [et al] |
| title_fullStr | Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to uroporphyria Amani, Farhat ... [et al] |
| title_full_unstemmed | Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to uroporphyria Amani, Farhat ... [et al] |
| title_short | Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to uroporphyria |
| title_sort | adverse outcome pathway on aryl hydrocarbon receptor activation leading to uroporphyria |
| topic | Environment Social Issues/Migration/Health |
| topic_facet | Environment Social Issues/Migration/Health |
| url | https://doi.org/10.1787/fde13d2c-en |
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