Uroporphyrinogen III decarboxylase

Uroporphyrinogen decarboxylase, also known as UROD, is an is_associated_with::enzyme that in humans is encoded by the UROD is_associated_with::gene.

Function
This gene encodes the fifth enzyme of the is_associated_with::heme biosynthetic pathway. This enzyme is responsible for catalyzing the conversion of is_associated_with::uroporphyrinogen to coproporphyrinogen through the removal of four carboxymethyl side chains.

Uroporphyrinogen III decarboxylase (UroD) is a homodimeric enzyme that catalyzes the fifth step in is_associated_with::heme biosynthesis: the elimination of is_associated_with::carboxyl groups from the four is_associated_with::acetate side chains of is_associated_with::uroporphyrinogen III to yield is_associated_with::coproporphyrinogen III.

Clinical significance
Mutations and deficiency in this enzyme are known to cause familial is_associated_with::porphyria cutanea tarda and is_associated_with::hepatoerythropoietic porphyria.

Mechanism
At low substrate concentrations, the reaction is believed to follow an ordered route, with the sequential removal of CO2 from the D, A, B, and C rings, whereas at higher substrate/enzyme levels a random route seems to be operative. The enzyme functions as a dimer in solution, and both the enzymes from human and tobacco have been crystallized and solved at good resolutions.

UroD is regarded as an unusual decarboxylase, since it performs decarboxylations without the intervention of any cofactors, unlike the vast majority of decarboxylases. Its mechanism has recently been proposed to proceed through substrate protonation by an is_associated_with::arginine residue. A 2008 report demonstrated that the uncatalyzed rate for UroD's reaction is 10−19 s−1, so at pH 10 the rate acceleration of UroD relative to the uncatalyzed rate, catalytic proficiency, is the largest for any enzyme known, 6 x 1024 M−1.