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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2018-03-02 22:28:25 UTC
HMDB IDHMDB0001261
Secondary Accession Numbers
  • HMDB01261
Metabolite Identification
Common NameCoproporphyrinogen III
DescriptionCoproporphyrinogen III is a porphyrin metabolite arising from heme synthesis. Porphyrins are pigments found in both animal and plant life. Coproporphyrinogen III is a tetrapyrrole dead-end product resulting from the spontaneous oxidation of the methylene bridges of coproporphyrinogen arising from heme synthesis. It is secreted in feces and urine. Coproporphyrinogen III is biosynthesized from the tetrapyrrole hydroxymethylbilane, which is converted by the action of uroporphyrinogen III synthase to uroporphyrinogen III. Uroporphyrinogen III is subsequently converted into coproporphyrinogen III through a series of four decarboxylations. Increased levels of coproporphyrinogens can indicate congenital erythropoietic porphyria or sideroblastic anemia, which are inherited disorders. Porphyria is a pathological state characterized by abnormalities of porphyrin metabolism and results in the excretion of large quantities of porphyrins in the urine and in extreme sensitivity to light. A large number of factors are capable of increasing porphyrin excretion, owing to different and multiple causes and etiologies: (1) the main site of the chronic hepatic porphyria disease process concentrates on the liver, (2) a functional and morphologic liver injury is almost regularly associated with this chronic porphyria, and (3) the toxic form due to occupational and environmental exposure takes mainly a subclinical course. Hepatic factors include disturbance in coproporphyrinogen metabolism, which results from inhibition of coproporphyrinogen oxidase as well as from the rapid loss and diminished utilization of coproporphyrinogen in the hepatocytes. This may also explain why coproporphyrin, its autoxidation product, predominates physiologically in the urine. Decreased biliary excretion of coproporphyrin leading to a compensatory urinary excretion. Therefore, the coproporphyrin ring isomer ratio (1:III) becomes a sensitive index for impaired liver function, intrahepatic cholestasis, and disturbed activity of hepatic uroporphyrinogen decarboxylase. In itself, secondary coproporphyrinuria is not associated with porphyria symptoms of a hepatologic-gastroenterologic, neurologic, or dermatologic order, even though coproporphyrinuria can occur with such symptoms (PMID: 3327428 ). Under certain conditions, coproporphyrinogen III can act as a phototoxin, a neurotoxin, and a metabotoxin. A phototoxin leads to cell damage upon exposure to light. A neurotoxin causes damage to nerve cells and nerve tissues. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of porphyrins are associated with porphyrias such as porphyria variegate, acute intermittent porphyria, hereditary coproporphyria (HCP), congenital erythropoietic porphyria, and sideroblastic anemia. In particular, coproporphyrinogen III is accumulated and excreted excessively in the feces in acute intermittent porphyria, protoporphyria, and variegate porphyria. There are several types of porphyrias (most are inherited). Hepatic porphyrias are characterized by acute neurological attacks (seizures, psychosis, extreme back and abdominal pain, and an acute polyneuropathy), while the erythropoietic forms present with skin problems (usually a light-sensitive blistering rash and increased hair growth). The neurotoxicity of porphyrins may be due to their selective interactions with tubulin, which disrupt microtubule formation and cause neural malformations (PMID: 3441503 ).
Structure
Thumb
Synonyms
ValueSource
3,8,13,17-Tetramethyl-5,10,15,20,22,24-hexahydroporphyrin-2,7,12,18-tetrapropionic acidChEBI
5,10,15,20,22,24-hexahydro-3,8,13,17-Tetramethyl-21H,23H-porphine-2,7,12,18-tetrapropanoic acidChEBI
COPROPORPHYRIN IIIChEBI
3,8,13,17-Tetramethyl-5,10,15,20,22,24-hexahydroporphyrin-2,7,12,18-tetrapropionateGenerator
5,10,15,20,22,24-hexahydro-3,8,13,17-Tetramethyl-21H,23H-porphine-2,7,12,18-tetrapropanoateGenerator
3,8,13,17-Tetramethyl-5,10,15,20,22,24-hexahydroporphyrin-2,7,12,18-tetrapropanoateHMDB
3,8,13,17-Tetramethyl-5,10,15,20,22,24-hexahydroporphyrin-2,7,12,18-tetrapropanoic acidHMDB
5,10,15,20,22,24-hexahydro-3,8,13,17-Tetramethyl-2,7,12,18-porphinetetrapropionateHMDB
5,10,15,20,22,24-hexahydro-3,8,13,17-Tetramethyl-2,7,12,18-porphinetetrapropionic acidHMDB
CoproporphyrinogenHMDB
Coproporphyrinogen-IIIHMDB
Chemical FormulaC36H44N4O8
Average Molecular Weight660.7566
Monoisotopic Molecular Weight660.315914404
IUPAC Name3-[9,14,20-tris(2-carboxyethyl)-5,10,15,19-tetramethyl-21,22,23,24-tetraazapentacyclo[16.2.1.1^{3,6}.1^{8,11}.1^{13,16}]tetracosa-1(20),3,5,8,10,13,15,18-octaen-4-yl]propanoic acid
Traditional Name3-[9,14,20-tris(2-carboxyethyl)-5,10,15,19-tetramethyl-21,22,23,24-tetraazapentacyclo[16.2.1.1^{3,6}.1^{8,11}.1^{13,16}]tetracosa-1(20),3,5,8,10,13,15,18-octaen-4-yl]propanoic acid
CAS Registry Number2624-63-7
SMILES
CC1=C2CC3=C(C)C(CCC(O)=O)=C(CC4=C(CCC(O)=O)C(C)=C(CC5=C(CCC(O)=O)C(C)=C(CC(N2)=C1CCC(O)=O)N5)N4)N3
InChI Identifier
InChI=1S/C36H44N4O8/c1-17-21(5-9-33(41)42)29-14-27-19(3)22(6-10-34(43)44)30(39-27)15-28-20(4)24(8-12-36(47)48)32(40-28)16-31-23(7-11-35(45)46)18(2)26(38-31)13-25(17)37-29/h37-40H,5-16H2,1-4H3,(H,41,42)(H,43,44)(H,45,46)(H,47,48)
InChI KeyNIUVHXTXUXOFEB-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as porphyrins. These are compounds containing a fundamental skeleton of four pyrrole nuclei united through the alpha-positions by four methine groups to form a macrocyclic structure.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassTetrapyrroles and derivatives
Sub ClassPorphyrins
Direct ParentPorphyrins
Alternative Parents
Substituents
  • Porphyrin
  • Tetracarboxylic acid or derivatives
  • Substituted pyrrole
  • Pyrrole
  • Heteroaromatic compound
  • Carboxylic acid derivative
  • Carboxylic acid
  • Azacycle
  • Carbonyl group
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Indirect biological role:

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.011 g/LALOGPS
logP1.96ALOGPS
logP4.89ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)3.8ChemAxon
Physiological Charge-4ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count8ChemAxon
Polar Surface Area212.36 ŲChemAxon
Rotatable Bond Count12ChemAxon
Refractivity181.86 m³·mol⁻¹ChemAxon
Polarizability72.85 ųChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0uxu-1000029000-41e3094ebb1945eeb049View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-002f-0000049000-0387f74262a47cf81121View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-05mn-0000095000-92704e3251119447de7cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-0000190000-117c439eaa250aa4b3b3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-002f-0000049000-0387f74262a47cf81121View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-05mn-0000095000-92704e3251119447de7cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-0000190000-117c439eaa250aa4b3b3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-052f-0000029000-96c0bca58c9caf08416fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-052g-1000079000-1da57e7f8a138a6c5516View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-052g-7000097000-2c52075e18d7d944ae80View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-052f-0000029000-96c0bca58c9caf08416fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-052g-1000079000-1da57e7f8a138a6c5516View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-052g-7000097000-2c52075e18d7d944ae80View in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biospecimen Locations
  • Blood
Tissue LocationNot Available
Pathways
NameSMPDB/PathwhizKEGG
Acute Intermittent PorphyriaThumbThumb?image type=greyscaleThumb?image type=simpleNot Available
Congenital Erythropoietic Porphyria (CEP) or Gunther DiseaseThumbThumb?image type=greyscaleThumb?image type=simpleNot Available
Hereditary Coproporphyria (HCP)ThumbThumb?image type=greyscaleThumb?image type=simpleNot Available
Porphyria Variegata (PV)ThumbThumb?image type=greyscaleThumb?image type=simpleNot Available
Porphyrin MetabolismThumbThumb?image type=greyscaleThumb?image type=simpleMap00860
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot Available
Normal
    details
    Abnormal Concentrations
    Not Available
    Associated Disorders and Diseases
    Disease ReferencesNone
    Associated OMIM IDsNone
    DrugBank IDNot Available
    Phenol Explorer Compound IDNot Available
    FoodDB IDFDB022518
    KNApSAcK IDC00007284
    Chemspider ID315
    KEGG Compound IDC03263
    BioCyc IDCOPROPORPHYRINOGEN_III
    BiGG ID41515
    Wikipedia LinkNot Available
    METLIN ID6116
    PubChem Compound321
    PDB IDCP3
    ChEBI ID15439
    References
    Synthesis ReferenceShoolingin-Jordan, Peter M. The biosynthesis of coproporphyrinogen III. Porphyrin Handbook (2003), 12 33-74.
    Material Safety Data Sheet (MSDS)Not Available
    General References
    1. Doss MO: Porphyrinurias and occupational disease. Ann N Y Acad Sci. 1987;514:204-18. [PubMed:3327428 ]
    2. Winkelman JW, Collins GH: Neurotoxicity of tetraphenylporphinesulfonate TPPS4 and its relation to photodynamic therapy. Photochem Photobiol. 1987 Nov;46(5):801-7. [PubMed:3441503 ]

    Enzymes

    General function:
    Involved in uroporphyrinogen decarboxylase activity
    Specific function:
    Catalyzes the decarboxylation of four acetate groups of uroporphyrinogen-III to yield coproporphyrinogen-III.
    Gene Name:
    UROD
    Uniprot ID:
    P06132
    Molecular weight:
    40786.58
    Reactions
    Uroporphyrinogen III → Coproporphyrinogen III + CO(2)details
    Uroporphyrinogen III → Coproporphyrinogen III + Carbon dioxidedetails
    General function:
    Involved in coproporphyrinogen oxidase activity
    Specific function:
    Key enzyme in heme biosynthesis. Catalyzes the oxidative decarboxylation of propionic acid side chains of rings A and B of coproporphyrinogen III.
    Gene Name:
    CPOX
    Uniprot ID:
    P36551
    Molecular weight:
    50151.605
    Reactions
    Coproporphyrinogen III + Oxygen + Hydrogen Ion → Protoporphyrinogen IX + CO(2) + Waterdetails
    Coproporphyrinogen III + Oxygen → Protoporphyrinogen IX + Carbon dioxide + Waterdetails
    General function:
    Involved in uroporphyrinogen-III synthase activity
    Specific function:
    Catalyzes cyclization of the linear tetrapyrrole, hydroxymethylbilane, to the macrocyclic uroporphyrinogen III, the branch point for the various sub-pathways leading to the wide diversity of porphyrins. Porphyrins act as cofactors for a multitude of enzymes that perform a variety of processes within the cell such as methionine synthesis (vitamin B12) or oxygen transport (heme).
    Gene Name:
    UROS
    Uniprot ID:
    P10746
    Molecular weight:
    28627.37
    General function:
    Involved in N-acetyltransferase activity
    Specific function:
    Probable acetyltransferase that binds the 5'-GGACTACAG- 3' sequence of coproporphyrinogen oxidase promoter. Able to activate transcription of a reporter construct in vitro
    Gene Name:
    NAT14
    Uniprot ID:
    Q8WUY8
    Molecular weight:
    21650.2