Cofactors

There are no Cofactors for this Enzyme

Reaction Mechanism

uroporphyrinogen decarboxylase By Reference

Uroporphyrinogen decarboxylase (HemE) catalyses the fifth step in heme biosynthesis by converting uroporphyrinogen III to coproporphyrinogen III by decarboxylating the four acetate side chains of the substrate.




The first step in the proposed mechanism is a proton transfer from an acid (Arg37) to the C2 centre of ring D. Computational studies suggest that this first step is rate limiting. The next step is the decarboxylation of the acetate moiety. The final catalytic step in the overall mechanism is regeneration of the protonated Arg37 residue by transfer of a proton from the substrate's --C₂H₂-- group to its neutral guanidino group with concurrent proton transfer from the guanidinium group of Arg50 to the C3′ centre of the substrate.

Catalytic Residues

AA	Uniprot	Uniprot Resid	PDB	PDB Resid
Arg	P06132	50	1uro	50
Arg	P06132	37	1uro	37
Arg	P06132	41	1uro	41
Asp	P06132	86	1uro	86
Tyr	P06132	164	1uro	164
View Reaction Mechanisms in M-CSA

Reaction Parameters

• Kinetic Parameters

  Organism	KM Value [mM]	Substrate	Comment
  Saccharomyces cerevisiae	0.000006	uroporphyrinogen III
  Euglena gracilis	0.00005	uroporphyrinogen III
  Homo sapiens	0.00005	5-COOH-porphyrinogen III
  Bos taurus	0.00042	6-COOH-porphyrinogen I
  Gallus gallus	0.0013	7-COOH-porphyrinogen

  View all in Brenda
• Temperature

  Organism	Temperature Range	Comment
  Rattus norvegicus	0 - 70	activity increases with temperature up to 47°C, decreases at 53°C
  Neohelice granulata	0 - 70	activity increases with temperature up to 47°C, decreases at 53°C

• pH

  Organism	pH Range	Comment
  Homo sapiens	5 - 8	in 0.2 M KH2PO4, 0.1 mM dithiothreitol
  Oryctolagus cuniculus	5.3 - 8	pH 5.3: about 60% of maximal activity, pH 8.0: about 65% of maximal activity
  Rattus norvegicus	6 - 8
  Gallus gallus	6 - 7.4	pH 6.0: about 55% of maximal activity, pH 7.4: about 50% of maximal activity, uroporphyrinogen III
  Cereibacter sphaeroides	6.2 - 7.7	pH 6.2: about 25% of maximal activity, pH 7.7: about 70% of maximal activity

  View all in Brenda

Associated Proteins

Citations

• A porphodimethene chemical inhibitor of uroporphyrinogen decarboxylase.
• Re: Porphyria Cutanea Tarda in a Patient with Myelofibrosis.
• Targeting uroporphyrinogen decarboxylase for head and neck cancer treatment
• Hepatoerythropoietic Porphyria Caused by a Novel Homoallelic Mutation in Uroporphyrinogen Decarboxylase Gene in Egyptian Patients.
• A Case Report of Porphyria Cutanea Tarda with Hepatitis-C Virus Co-infection.
• Structural aspects of enzymes involved in prokaryotic Gram-positive heme biosynthesis.
• Development and validation of metabolic models for predicting survival and immune status of hepatocellular carcinoma patients.
• Improved biosynthesis of heme in Bacillus subtilis through metabolic engineering assisted fed-batch fermentation.
• Uroporphyrinogen decarboxylase: optimizing radiotherapy for head and neck cancer.
• Thiol redox sensitivity of two key enzymes of heme biosynthesis and pentose phosphate pathways: uroporphyrinogen decarboxylase and transketolase.
• Applications of the Whole-Cell System in the Efficient Biosynthesis of Heme.