Uroporphyrinogen decarboxylase

Uroporphyrinogen Decarboxylase

Uroporphyrinogen decarboxylase (UROD) is an enzyme that plays a crucial role in the heme biosynthesis pathway. It catalyzes the conversion of uroporphyrinogen III to coproporphyrinogen III by decarboxylating the four acetate groups to methyl groups. This step is essential for the production of heme, which is a vital component of hemoglobin, myoglobin, and various cytochromes.

Structure

Uroporphyrinogen decarboxylase is a homodimeric enzyme, meaning it consists of two identical subunits. Each subunit contains a binding site for the substrate, uroporphyrinogen III. The enzyme's active site is highly conserved and is responsible for the decarboxylation reaction.

Function

The primary function of UROD is to facilitate the conversion of uroporphyrinogen III to coproporphyrinogen III. This reaction involves the removal of four carboxyl groups as carbon dioxide, resulting in the formation of coproporphyrinogen III, which is then further processed in the heme biosynthesis pathway.

Clinical Significance

Deficiency or dysfunction of uroporphyrinogen decarboxylase is associated with a condition known as Porphyria cutanea tarda (PCT). PCT is the most common type of porphyria and is characterized by photosensitivity, skin fragility, and blistering. It is often triggered by factors such as alcohol consumption, liver disease, and exposure to certain chemicals.

Genetic Aspects

The UROD gene, located on chromosome 1, encodes the uroporphyrinogen decarboxylase enzyme. Mutations in this gene can lead to reduced enzyme activity and are implicated in familial cases of porphyria cutanea tarda. Genetic testing can identify mutations in the UROD gene, aiding in the diagnosis and management of the condition.

Biochemical Pathway

Uroporphyrinogen decarboxylase is part of the heme biosynthesis pathway, which involves several enzymatic steps:

1. ALA Synthase: Converts glycine and succinyl-CoA to δ-aminolevulinic acid (ALA). 2. ALA Dehydratase: Converts ALA to porphobilinogen. 3. Porphobilinogen Deaminase: Converts porphobilinogen to hydroxymethylbilane. 4. Uroporphyrinogen III Synthase: Converts hydroxymethylbilane to uroporphyrinogen III. 5. Uroporphyrinogen Decarboxylase: Converts uroporphyrinogen III to coproporphyrinogen III. 6. Coproporphyrinogen Oxidase: Converts coproporphyrinogen III to protoporphyrinogen IX. 7. Protoporphyrinogen Oxidase: Converts protoporphyrinogen IX to protoporphyrin IX. 8. Ferrochelatase: Inserts iron into protoporphyrin IX to form heme.

Also see

• Heme synthesis
• Porphyria
• Enzyme
• Metabolic pathway