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Oxidation, Uroporphyrinogen leads to Accumulation, Highly carboxylated porphyrins
Key Event Relationship Overview
AOPs Referencing Relationship
Life Stage Applicability
Key Event Relationship Description
When the normal heme biosynthesis pathway is disrupted, heme precursors are oxidized to highly stable porphyrins, which accumulate in the liver, kidneys, spleen, skin and blood; porphyrin excretion in urine and feces is also elevated. The pattern of porphyrin accumulation is indicative of which enzyme in the heme pathway is predominately affected. Chemical induced porphyria often involves the inhibition of uroporphyrinogen decarboxylase (UROD), which leads to the accumulation of uroporphyrin and hepta- and hexacarboxylic acid porphyrins (highly carboxylated porphyrins).
Evidence Collection Strategy
Evidence Supporting this KER
Each of the four acetic acid substituents of porphyrinogen is decarboxylated in sequence with the consequent formation of hepta-, hexa-, and pentacarboxylic porphyrinogens as intermediates. Oxidation of these intermediates results in their corresponding, highly stable porphyrins, which accumulate.
Uncertainties and Inconsistencies
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
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