protoporphyrinogen IX biosynthetic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of protoporphyrinogen IX. [GOC:go_curators]

Protoporphyrinogen IX biosynthesis is a crucial metabolic pathway responsible for the synthesis of heme, a vital prosthetic group found in hemoglobin, myoglobin, cytochromes, and other heme proteins. Heme plays a critical role in oxygen transport, electron transport, and cellular respiration. The biosynthesis of protoporphyrinogen IX involves a series of enzymatic reactions that convert the amino acid glycine and succinyl CoA to protoporphyrinogen IX.

The pathway begins with the condensation of glycine and succinyl CoA to form α-amino-β-ketoadipate. This reaction is catalyzed by the enzyme δ-aminolevulinate synthase (ALAS). α-amino-β-ketoadipate is then decarboxylated to δ-aminolevulinate (ALA) by the enzyme α-amino-β-ketoadipate decarboxylase. Two molecules of ALA condense to form porphobilinogen (PBG) in a reaction catalyzed by the enzyme porphobilinogen synthase (hydroxymethylbilane synthase). Four molecules of PBG then assemble into a linear tetrapyrrole known as protoporphyrinogen IX through a series of enzymatic steps.

The biosynthesis of protoporphyrinogen IX is tightly regulated to ensure adequate heme production while preventing the accumulation of toxic intermediates. The first committed step in the pathway, catalyzed by ALAS, is subject to feedback inhibition by heme. This regulation ensures that heme synthesis is only initiated when necessary. In addition, the enzyme ferrochelatase, which catalyzes the final step in heme synthesis, is also regulated by heme levels.

Defects in protoporphyrinogen IX biosynthesis can lead to a variety of human diseases known as porphyrias. These disorders result from the accumulation of porphyrin precursors in erythrocytes, body fluids, and tissues. Symptoms of porphyrias can vary depending on the specific enzyme deficiency and the amount of porphyrin precursors accumulated. Some common symptoms include photosensitivity, abdominal pain, neurological disorders, and skin lesions.

The protoporphyrinogen IX biosynthetic pathway is a complex and tightly regulated process that is essential for life. It is a fascinating example of how metabolic pathways are integrated into cellular function and how defects in these pathways can lead to human disease. '
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Proteins (5)

Compounds (11)