Uroporphyrinogen III synthase

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  Uroporphyrinogen III synthase structure

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  Crystal structure of Uroporphyrinogen III synthase

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  Heme synthesis pathway

Uroporphyrinogen III Synthase

Uroporphyrinogen III synthase is an enzyme that plays a crucial role in the biosynthesis of heme and chlorophyll. It catalyzes the conversion of hydroxymethylbilane to uroporphyrinogen III, a key intermediate in the pathway leading to the production of these essential biological pigments.

Function

Uroporphyrinogen III synthase is responsible for the cyclization and rearrangement of hydroxymethylbilane, a linear tetrapyrrole, into uroporphyrinogen III, a cyclic tetrapyrrole. This reaction is a critical step in the porphyrin biosynthesis pathway, which ultimately leads to the formation of heme and chlorophyll. The enzyme ensures the correct asymmetric arrangement of the pyrrole rings, which is essential for the biological function of the final products.

Mechanism

The enzyme operates by facilitating the closure of the linear tetrapyrrole chain into a macrocyclic structure. This involves the formation of a covalent bond between the terminal pyrrole rings, followed by a rearrangement that results in the inversion of one of the pyrrole rings. This inversion is crucial for the production of uroporphyrinogen III rather than the symmetric uroporphyrinogen I, which is not used in heme biosynthesis.

Clinical Significance

Deficiency or malfunction of uroporphyrinogen III synthase can lead to a group of disorders known as porphyrias. One such disorder is congenital erythropoietic porphyria (CEP), also known as Gunther's disease. CEP is characterized by the accumulation of porphyrins in the body, leading to symptoms such as photosensitivity, hemolytic anemia, and red-colored urine. The condition arises due to the accumulation of uroporphyrinogen I, which is formed when the enzyme is deficient or inactive.

Related Enzymes

Uroporphyrinogen III synthase is part of a larger family of enzymes involved in porphyrin metabolism. Other key enzymes in this pathway include:

• Porphobilinogen deaminase
• Uroporphyrinogen decarboxylase
• Coproporphyrinogen oxidase
• Protoporphyrinogen oxidase

Each of these enzymes plays a specific role in the stepwise conversion of simple precursors into complex porphyrin structures.

Related Pages

• Heme biosynthesis
• Porphyrin
• Congenital erythropoietic porphyria
• Porphyria