Protoporphyrin IX (T3D4440)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (1)XML
Targets (1)
Record Information
Version2.0
Creation Date2014-08-29 06:51:17 UTC
Update Date2018-03-21 17:46:21 UTC
Accession NumberT3D4440
Identification
Common NameProtoporphyrin IX
ClassSmall Molecule
DescriptionProtoporphyrins are tetrapyrroles containing 4 methyl, 2 propionic, and 2 vinyl side chains. Protoporphyrin is produced by oxidation of the methylene bridge of protoporphyrinogen. Protoporphyrin IX is the only naturally occurring isomer; it is an intermediate in heme biosynthesis, combining with ferrous iron to form protoheme IX, the heme prosthetic group of hemoglobin. Protoporphyrin IX is created by the enzyme protoporphyrinogen oxidase. The enzyme ferrochelatase converts it into heme. Protoporphyrin IX naturally occurs in small amounts in feces. Protoporphyrin IX is also responsible for the brown pigment (ooporphyrin) of birds' eggs. Protoporphyrin IX is used as a branch point in the biosynthetic pathway leading to heme (by insertion of iron) and chlorophylls (by insertion of Mg and further side-chain transformation). Protoporphyrin IX can be used to treat liver disorders, mainly as the sodium salt. Under certain conditions, protoporphyrin IX can act as a neurotoxin, a phototoxin, and a metabotoxin. A neurotoxin causes damage to nerve cells and nerve tissues. A phototoxin causes cell damage upon exposure to light. 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, and hereditary coproporphyria (HCP). In particular, it 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).
Compound Type
  • Animal Toxin
  • Drug
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
3,3'-(3,7,12,17-Tetramethyl-8,13-divinyl-21H,23H-porphine-2,18-diyl)-bis-propionate
3,3'-(3,7,12,17-Tetramethyl-8,13-divinyl-21H,23H-porphine-2,18-diyl)-bis-propionic acid
3,3'-(3,7,12,17-Tetramethyl-8,13-divinylporphine-2,18-diyl)di
Kammerer'S prophyrin
Ooporphyrin
Porphyrinogen IX
PpIX
Protoporphyrin
Protoporphyrin-IX
Chemical FormulaC34H34N4O4
Average Molecular Mass562.658 g/mol
Monoisotopic Mass562.258 g/mol
CAS Registry Number553-12-8
IUPAC Name3-[20-(2-carboxyethyl)-9,14-diethenyl-5,10,15,19-tetramethyl-21,22,23,24-tetraazapentacyclo[16.2.1.1^{3,6}.1^{8,11}.1^{13,16}]tetracosa-1(21),2,4,6,8(23),9,11,13,15,17,19-undecaen-4-yl]propanoic acid
Traditional Name3-[20-(2-carboxyethyl)-9,14-diethenyl-5,10,15,19-tetramethyl-21,22,23,24-tetraazapentacyclo[16.2.1.1^{3,6}.1^{8,11}.1^{13,16}]tetracosa-1(21),2,4,6,8(23),9,11,13,15,17,19-undecaen-4-yl]propanoic acid
SMILES[H]\C-1=C2\N\C(=C([H])/C3=N/C(=C([H])\C4=C(C)C(CCC(O)=O)=C(N4)\C([H])=C4/N=C-1C(C)=C4CCC(O)=O)/C(C=C)=C3C)C(C=C)=C2C
InChI IdentifierInChI=1S/C34H34N4O4/c1-7-21-17(3)25-13-26-19(5)23(9-11-33(39)40)31(37-26)16-32-24(10-12-34(41)42)20(6)28(38-32)15-30-22(8-2)18(4)27(36-30)14-29(21)35-25/h7-8,13-16,35,38H,1-2,9-12H2,3-6H3,(H,39,40)(H,41,42)/b25-13-,26-13-,27-14-,28-15-,29-14-,30-15-,31-16-,32-16-
InChI KeyInChIKey=KSFOVUSSGSKXFI-UJJXFSCMSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as porphyrins. Porphyrins 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 ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Membrane
  • Mitochondria
Biofluid LocationsNot Available
Tissue Locations
  • Adipose Tissue
  • Adrenal Medulla
  • Bladder
  • Erythrocyte
  • Fibroblasts
  • Gastrointestinal Tract
  • Intestine
  • Kidney
  • Liver
  • Lymphocyte
  • Platelet
  • Skin
  • Spleen
  • Stratum Corneum
  • T-Lymphocyte
  • Testes
  • Thyroid Gland
  • Urinary Bladder
Pathways
NameSMPDB LinkKEGG Link
Porphyrin MetabolismSMP00024 map00860
Porphyria Variegata (PV)SMP00346 Not Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point300°C
Boiling PointNot Available
Solubility0.169 mg/mL at 25°C
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.022 g/LALOGPS
logP4.4ALOGPS
logP6.78ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)3.68ChemAxon
pKa (Strongest Basic)4.96ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area131.96 ŲChemAxon
Rotatable Bond Count8ChemAxon
Refractivity163.81 m³·mol⁻¹ChemAxon
Polarizability66.03 ųChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0uxu-1000290000-e22236fe3cca8eed1ecf2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00di-6000094000-b9c12952e100c5144cab2017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS ("Protoporphyrin IX,1TMS,#1" TMS) - 70eV, PositiveNot Available2021-10-14View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_4) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_1) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_3) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_4) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_5) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_6) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_4) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_2_1) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_2_2) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_2_3) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_2_4) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_2_5) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_2_6) - 70eV, PositiveNot Available2021-10-15View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0000090000-5d5be53410134c5719ab2017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00kb-1000590000-2d4157b9f73534d95a9c2017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4l-1000910000-07524a9291a1921dfafc2017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0000090000-5df26c1cfb9a0b16a91a2017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0296-1000190000-2d4bcb49201fc10adc092017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4l-9000230000-064fb944a966d08c06bf2017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0000090000-87c1740ecd1a28f4a2d92021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03xu-0000590000-99160b987bb7e62ab3622021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00di-0000900000-f2d9118441a9c8c47d792021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03dj-0000090000-d428ac6dc2fc4794cc412021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0j4j-0000090000-2b065966ec57bb97d5112021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0uk9-1000970000-b435817e4dc349e65ab32021-09-23View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, H2O, predicted)Not Available2022-08-21View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityNot Available
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesThis is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.
Minimum Risk LevelNot Available
Health EffectsChronically high levels of porophyrins are associated with porphyrias such as Porphyria variegate, Acute Intermittent Porphyria and Hereditary Coproporphyria (HCP).
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB02285
HMDB IDHMDB00241
PubChem Compound IDNot Available
ChEMBL IDCHEMBL1325592
ChemSpider ID10469486
KEGG IDC02191
UniProt IDNot Available
OMIM ID
ChEBI ID15430
BioCyc IDPROTOPORPHYRIN_IX
CTD IDNot Available
Stitch IDNot Available
PDB IDPP9
ACToR IDNot Available
Wikipedia LinkProtoporphyrin IX
References
Synthesis Reference

Elaine A. Best, Charles Lee Hershberger, Christopher Carl Frye, “Methods of reducing the levels of protoporphyrin IX in recombinant hemoglobin preparations.” U.S. Patent US6136565, issued April, 1998.

MSDSLink
General References
  1. Messmann H, Knuchel R, Baumler W, Holstege A, Scholmerich J: Endoscopic fluorescence detection of dysplasia in patients with Barrett's esophagus, ulcerative colitis, or adenomatous polyps after 5-aminolevulinic acid-induced protoporphyrin IX sensitization. Gastrointest Endosc. 1999 Jan;49(1):97-101. [9869731 ]
  2. Stankiewicz A, Lutz W, Krajewska B, Szulc B: [Plasma indicators of iron metabolism in persons occupationally exposed to organic solvents with normal and increased levels of protoporphyrin IX in erythrocytes]. Pol Tyg Lek. 1986 Jul 7;41(27):851-4. [3763462 ]
  3. Stankiewicz A: [Erythrocyte protoporphyrin IX in occupational exposure to asbestos]. Med Pr. 1984;35(5):351-4. [6530952 ]
  4. Sudworth CD, Stringer MR, Cruse-Sawyer JE, Brown SB: Fluorescence microspectroscopy technique for the study of intracellular protoporphyrin IX dynamics. Appl Spectrosc. 2003 Jun;57(6):682-8. [14658702 ]
  5. Kufner G, Schlegel H, Jager R: A spectrophotometric micromethod for determining erythrocyte protoporphyrin-IX in whole blood or erythrocytes. Clin Chem Lab Med. 2005;43(2):183-91. [15843214 ]
  6. Stankiewicz A: The concentration of protoporphyrin IX in workers occupationally exposed to lead. Mater Med Pol. 1989 Apr-Jun;21(2):100-2. [2488459 ]
  7. Krieg RC, Fickweiler S, Wolfbeis OS, Knuechel R: Cell-type specific protoporphyrin IX metabolism in human bladder cancer in vitro. Photochem Photobiol. 2000 Aug;72(2):226-33. [10946577 ]
  8. Bailey GG, Needham LL: Simultaneous quantification of erythrocyte zinc protoporphyrin and protoporphyrin IX by liquid chromatography. Clin Chem. 1986 Dec;32(12):2137-42. [3779978 ]
  9. Chisolm J Jr, Brown DH: Micro-scale photofluorometric determination of "free erythrocyte pophyrin" (protoporphyrin IX). Clin Chem. 1975 Oct;21(11):1669-82. [1164799 ]
  10. Casas A, Batlle AM, Butler AR, Robertson D, Brown EH, MacRobert A, Riley PA: Comparative effect of ALA derivatives on protoporphyrin IX production in human and rat skin organ cultures. Br J Cancer. 1999 Jul;80(10):1525-32. [10408393 ]
  11. Smits T, Robles CA, van Erp PE, van de Kerkhof PC, Gerritsen MJ: Correlation between macroscopic fluorescence and protoporphyrin IX content in psoriasis and actinic keratosis following application of aminolevulinic acid. J Invest Dermatol. 2005 Oct;125(4):833-9. [16185285 ]
  12. Bartosova J, Hrkal Z: Accumulation of protoporphyrin-IX (PpIX) in leukemic cell lines following induction by 5-aminolevulinic acid (ALA). Comp Biochem Physiol C Toxicol Pharmacol. 2000 Jul;126(3):245-52. [11048674 ]
  13. Sakai T, Takeuchi Y, Ikeya Y, Araki T, Ushio K: [Automated HPLC method for determining zinc protoporphyrin IX and protoporphyrin IX in erythrocytes of workers exposed to lead]. Sangyo Igaku. 1988 Nov;30(6):467-74. [3221502 ]
  14. Stankiewicz A, Lutz W, Szeszko A: [Protoporphyrin IX level in erythrocytes of persons with alcoholic liver cirrhosis]. Pol Tyg Lek. 1985 Jul 15;40(28):787-9. [4059100 ]
  15. Star WM, Aalders MC, Sac A, Sterenborg HJ: Quantitative model calculation of the time-dependent protoporphyrin IX concentration in normal human epidermis after delivery of ALA by passive topical application or lontophoresis. Photochem Photobiol. 2002 Apr;75(4):424-32. [12003134 ]
  16. von Beckerath M, Juzenas P, Ma LW, Iani V, Lofgren L, Moan J: The influence of UV exposure on 5-aminolevulinic acid-induced protoporphyrin IX production in skin. Photochem Photobiol. 2001 Dec;74(6):825-8. [11783939 ]
  17. Gottsch JD, Graham CR Jr, Hairston RJ, Chen CH, Green WR, Stark WJ: Protoporphyrin IX photosensitization of corneal endothelium. Arch Ophthalmol. 1989 Oct;107(10):1497-500. [2803100 ]
  18. Bissonnette R, Zeng H, McLean DI, Korbelik M, Lui H: Oral aminolevulinic acid induces protoporphyrin IX fluorescence in psoriatic plaques and peripheral blood cells. Photochem Photobiol. 2001 Aug;74(2):339-45. [11547574 ]
  19. Rick K, Sroka R, Stepp H, Kriegmair M, Huber RM, Jacob K, Baumgartner R: Pharmacokinetics of 5-aminolevulinic acid-induced protoporphyrin IX in skin and blood. J Photochem Photobiol B. 1997 Oct;40(3):313-9. [9372622 ]
  20. De Rosa FS, Marchetti JM, Thomazini JA, Tedesco AC, Bentley MV: A vehicle for photodynamic therapy of skin cancer: influence of dimethylsulphoxide on 5-aminolevulinic acid in vitro cutaneous permeation and in vivo protoporphyrin IX accumulation determined by confocal microscopy. J Control Release. 2000 Apr 3;65(3):359-66. [10699294 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Ferritin light chain
General Function:
Iron ion binding
Specific Function:
Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role in delivery of iron to cells. Mediates iron uptake in capsule cells of the developing kidney (By similarity).
Gene Name:
FTL
Uniprot ID:
P02792
Molecular Weight:
20019.49 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]