WordNet

any of the enzymes that hydrolize the carboxyl group

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/05/01 04:28:27」(JST)

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Uroporphyrinogen decarboxylase, also known as UROD, is an enzyme that in humans is encoded by the UROD gene.^[1]

Function

This gene encodes the fifth enzyme of the heme biosynthetic pathway. This enzyme is responsible for catalyzing the conversion of uroporphyrinogen to coproporphyrinogen through the removal of four carboxymethyl side chains.^[1]

Uroporphyrinogen III decarboxylase (UroD) is a homodimeric enzyme (EC 4.1.1.37, PDB 1URO) that catalyzes the fifth step in heme biosynthesis: the elimination of carboxyl groups from the four acetate side chains of uroporphyrinogen III to yield coproporphyrinogen III.

Clinical significance

Mutations and deficiency in this enzyme are known to cause familial porphyria cutanea tarda and hepatoerythropoietic porphyria.^[1]

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.

The reaction catalyzed by UroD

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 residue.^[2] 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.^[3]

Proposed reaction mechanism of uroporphyrinogen III decarboxyklase

References

^ ^a ^b ^c "Entrez Gene: UROD uroporphyrinogen decarboxylase".
^ Silva PJ, Ramos MJ. Density-functional study of mechanisms for the cofactor-free decarboxylation performed by uroporphyrinogen III decarboxylase. J Phys Chem B 2005;109:18195-200. doi:10.1021/jp051792s.
^ Lewis CA, Wolfenden R (November 2008). "Uroporphyrinogen decarboxylation as a benchmark for the catalytic proficiency of enzymes". Proc. Natl. Acad. Sci. U.S.A. 105 (45): 17328–33. doi:10.1073/pnas.0809838105. PMC 2582308. PMID 18988736.

UpToDate Contents

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1. Porphyria cutanea tarda and hepatoerythropoietic porphyria: Clinical manifestations and diagnosis
2. Porphyria cutanea tarda and hepatoerythropoietic porphyria: Management and prognosis
3. ポルフィリン症：概要 porphyrias an overview
4. 先天性骨髄性ポルフィリン症 congenital erythropoietic porphyria
5. 偽ポルフィリン症 pseudoporphyria

English Journal

Porphyria cutanea tarda in a child following multi-agent chemotherapy.

Lapresto L, Nyanda H, Knapp CF, Sopkovich J, Nelson CG.AbstractPorphyria cutanea tarda (PCT) is a blistering skin disorder that occurs most commonly in middle-aged individuals. It is caused by decreased uroporphyrinogen decarboxylase (UROD) activity, which results in elevated levels of uroporphyrinogen. Occurrence remains very rare in children with some sources quoting as few as 50 reports of childhood cases.1 The literature reports occasional cases of PCT onset with various drugs, including barbiturates, estrogens, griseofulvin, rifampicin, sulfonamides, imatinib, methotrexate, tamoxifen, and cyclophosphamide, however its incidence in childhood is uncommon.2-6 We present a case of new-onset PCT in an eight year-old following treatment of pre-B cell acute lymphoblastic leukemia with multi-agent chemotherapy.<BR /><BR /> <EM>J Drugs Dermatol.</EM> 2014;13(4):489-491.
Journal of drugs in dermatology : JDD.J Drugs Dermatol.2014 Apr 1;13(4):489-91.
Porphyria cutanea tarda (PCT) is a blistering skin disorder that occurs most commonly in middle-aged individuals. It is caused by decreased uroporphyrinogen decarboxylase (UROD) activity, which results in elevated levels of uroporphyrinogen. Occurrence remains very rare in children with some sources
PMID 24719070

Hepatitis C- and HIV-induced porphyria cutanea tarda.

Quansah R, Cooper CJ, Said S, Bizet J, Paez D, Hernandez GT.Author information Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX, U.S.A.AbstractPatient: Male, 47 Final Diagnosis: Porphyria cutanea tarda Symptoms: Chills • cough dry • thumb swelling Medication: - Clinical Procedure: - Specialty: Metabolic Disorders and Diabetics.
The American journal of case reports.Am J Case Rep.2014 Jan 21;15:35-40. doi: 10.12659/AJCR.889955. eCollection 2014.
Patient: Male, 47 Final Diagnosis: Porphyria cutanea tarda Symptoms: Chills • cough dry • thumb swelling Medication: - Clinical Procedure: - Specialty: Metabolic Disorders and Diabetics.OBJECTIVE: Challenging differential diagnosis.BACKGROUND: Porphyria cutanea tarda (PCT) is the most common typ
PMID 24470839

A porphodimethene chemical inhibitor of uroporphyrinogen decarboxylase.

Yip KW1, Zhang Z2, Sakemura-Nakatsugawa N1, Huang JW3, Vu NM2, Chiang YK3, Lin CL3, Kwan JY1, Yue S1, Jitkova Y1, To T1, Zahedi P1, Pai EF4, Schimmer AD5, Lovell JF6, Sessler JL2, Liu FF7.Author information 1Ontario Cancer Institute/Campbell Family Cancer Research Institute, University Health Network (UHN), Toronto, Ontario, Canada.2Department of Chemistry, Institute for Cellular and Molecular Biology, the University of Texas at Austin, Austin, Texas, United States of America.3Biomedical Technology and Device Research Labs, Industrial Technology Research Institute, Hsin-chu, Taiwan.4Ontario Cancer Institute/Campbell Family Cancer Research Institute, University Health Network (UHN), Toronto, Ontario, Canada ; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada ; Department of Biochemistry, University of Toronto, Ontario, Canada ; Department of Molecular Genetics; University of Toronto, Ontario, Canada.5Ontario Cancer Institute/Campbell Family Cancer Research Institute, University Health Network (UHN), Toronto, Ontario, Canada ; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.6Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York, United States of America.7Ontario Cancer Institute/Campbell Family Cancer Research Institute, University Health Network (UHN), Toronto, Ontario, Canada ; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada ; Department of Radiation Oncology, Princess Margaret Cancer Centre, UHN, Toronto, Ontario, Canada ; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.AbstractUroporphyrinogen decarboxylase (UROD) catalyzes the conversion of uroporphyrinogen to coproporphyrinogen during heme biosynthesis. This enzyme was recently identified as a potential anticancer target; its inhibition leads to an increase in reactive oxygen species, likely mediated by the Fenton reaction, thereby decreasing cancer cell viability and working in cooperation with radiation and/or cisplatin. Because there is no known chemical UROD inhibitor suitable for use in translational studies, we aimed to design, synthesize, and characterize such a compound. Initial in silico-based design and docking analyses identified a potential porphyrin analogue that was subsequently synthesized. This species, a porphodimethene (named PI-16), was found to inhibit UROD in an enzymatic assay (IC50 = 9.9 µM), but did not affect porphobilinogen deaminase (at 62.5 µM), thereby exhibiting specificity. In cellular assays, PI-16 reduced the viability of FaDu and ME-180 cancer cells with half maximal effective concentrations of 22.7 µM and 26.9 µM, respectively, and only minimally affected normal oral epithelial (NOE) cells. PI-16 also combined effectively with radiation and cisplatin, with potent synergy being observed in the case of cisplatin in FaDu cells (Chou-Talalay combination index <1). This work presents the first known synthetic UROD inhibitor, and sets the foundation for the design, synthesis, and characterization of higher affinity and more effective UROD inhibitors.
PloS one.PLoS One.2014 Feb 25;9(2):e89889. doi: 10.1371/journal.pone.0089889. eCollection 2014.
Uroporphyrinogen decarboxylase (UROD) catalyzes the conversion of uroporphyrinogen to coproporphyrinogen during heme biosynthesis. This enzyme was recently identified as a potential anticancer target; its inhibition leads to an increase in reactive oxygen species, likely mediated by the Fenton react
PMID 24587102

Japanese Journal

色素関係ウロポルフィリノーゲン脱炭酸酵素(UROD) (広範囲血液・尿化学検査,免疫学的検査(第7版・1)その数値をどう読むか) -- (生化学的検査(1))

近藤雅雄
日本臨床 67(-) (968), 787-789, 2009-12
NAID 40016874615

Interaction of the Molecular Chaperone HtpG with Uroporphyrinogen Decarboxylase in the Cyanobacterium Synechococcus elongatus PCC 7942

SAITO Masakazu,WATANABE Satoru,YOSHIKAWA Hirofumi,NAKAMOTO Hitoshi
Bioscience, biotechnology, and biochemistry 72(5), 1394-1397, 2008-05-23
… Uroporphyrinogen decarboxylase (HemE) is important due to its location at the first branch-point in tetrapyrrole biosynthesis. …
NAID 10027528269

Related Pictures

★リンクテーブル★

リンク元	「ウロポルフィリノーゲン脱炭酸酵素」「UROD」「UROD deficiency」
関連記事	「decarboxylase」「uroporphyrinogen」

「ウロポルフィリノーゲン脱炭酸酵素」

Uroporphyrinogen decarboxylase
	; PDB rendering based on 1jph.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1JPH, 1JPI, 1JPK, 1R3Q, 1R3R, 1R3S, 1R3T, 1R3V, 1R3W, 1R3Y, 1URO, 2Q6Z, 2Q71, 3GVQ, 3GVR, 3GVV, 3GVW, 3GW0, 3GW3
Identifiers
Symbols	UROD ; PCT; UPD
External IDs	OMIM: 613521 MGI: 98916 HomoloGene: 320 ChEMBL: 1681619 GeneCards: UROD Gene
EC number	4.1.1.37
Gene ontology
Molecular function	• uroporphyrinogen decarboxylase activity;
Cellular component	• nucleus; • nucleolus; • cytoplasm; • cytosol; • microtubule cytoskeleton;
Biological process	• porphyrin-containing compound metabolic process; • protoporphyrinogen IX biosynthetic process; • heme biosynthetic process; • small molecule metabolic process;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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