Uroporphyrinogen III decarboxylase (uroporphyrinogen decarboxylase, or UROD) is an
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
() that in humans is encoded by the ''UROD''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Function
Uroporphyrinogen III decarboxylase is a homodimeric enzyme () that catalyzes the fifth step in
heme
Heme (American English), or haem (Commonwealth English, both pronounced /Help:IPA/English, hi:m/ ), is a ring-shaped iron-containing molecule that commonly serves as a Ligand (biochemistry), ligand of various proteins, more notably as a Prostheti ...
biosynthesis, which corresponds to the elimination of
carboxyl groups from the four
acetate
An acetate is a salt formed by the combination of acetic acid with a base (e.g. alkaline, earthy, metallic, nonmetallic, or radical base). "Acetate" also describes the conjugate base or ion (specifically, the negatively charged ion called ...
side chains of
uroporphyrinogen III to yield
coproporphyrinogen III:
:
uroporphyrinogen III coproporphyrinogen III + 4 CO
2
Clinical significance
Mutations and deficiency in this enzyme are known to cause familial
porphyria cutanea tarda and
hepatoerythropoietic porphyria.
At least 65 disease-causing mutations in this gene have been discovered.
Mechanism
At low substrate concentrations, the reaction is believed to follow an ordered route, with the sequential removal of CO
2 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
arginine
Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...
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, i.e. catalytic proficiency, is the largest for any enzyme known, 6 x 10
24 M
−1.
References
Further reading
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External links
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EC 4.1.1