Uroporphyrinogen III decarboxylase

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Uroporphyrinogen III decarboxylase (UROD) is an enzyme in the body’s heme biosynthesis pathway. Heme is the iron-containing component of blood and many other proteins.

What it does
UROD removes four carboxyl groups from uroporphyrinogen III, turning it into coproporphyrinogen III. It works as a homodimer, meaning two identical subunits come together to do the job, and it does not need any helper cofactors to function.

Where the gene is
In humans, the UROD gene encodes this enzyme. It is located on chromosome 1p34.1. The enzyme is very similar in many animals, including mice.

Why it matters
Mutations in UROD can cause disorders such as familial porphyria cutanea tarda and hepatoerythropoietic porphyria. More than 65 disease-causing mutations have been identified.

How the reaction works
At low substrate levels, UROD removes the carboxyl groups in a specific, ordered sequence from the D, A, B, and C rings. At higher substrate or enzyme levels, the process can proceed in a less ordered, random way.

Unusual features and mechanism
UROD is unusual because it can perform decarboxylation without any cofactors. A proposed mechanism involves a substrate being protonated by an arginine residue in the enzyme.

How efficient is it
The uncatalyzed reaction is extremely slow. UROD makes the reaction happen about a billion billion times faster, one of the largest catalytic improvements known for any enzyme.

Structural references
UROD forms a stable dimer in solution, and high-resolution structures have been solved for human and tobacco versions of the enzyme. The structure is also represented by a known entry in structural databases.