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Record Information
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2020-04-23 20:56:37 UTC
Secondary Accession Numbers
  • HMDB00241
Metabolite Identification
Common NameProtoporphyrin IX
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 ).
3,3'-(3,7,12,17-Tetramethyl-8,13-divinyl-21H,23H-porphine-2,18-diyl)-bis-propionic acidChEBI
3,7,12,17-Tetramethyl-8,13-divinylporphyrin-2,18-dipropanoic acidChEBI
Kammerer's prophyrinChEBI
Porphyrinogen IXChEBI
Chemical FormulaC34H34N4O4
Average Molecular Weight562.6582
Monoisotopic Molecular Weight562.258005596
IUPAC Name3-[20-(2-carboxyethyl)-9,14-diethenyl-5,10,15,19-tetramethyl-21,22,23,24-tetraazapentacyclo[³,⁶.1⁸,¹¹.1¹³,¹⁶]tetracosa-1(21),2,4,6,8(23),9,11,13,15,17,19-undecaen-4-yl]propanoic acid
Traditional Nameprotoporphyrin
CAS Registry Number553-12-8
InChI Identifier
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
Physiological effect

Health effect:


Route of exposure:


Biological location:


Naturally occurring process:


Indirect biological role:

Biological role:

Industrial application:

Physical Properties
Experimental Properties
Melting Point300 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.17 mg/mL at 25 °CNot Available
LogPNot AvailableNot Available
Predicted Properties
Water Solubility0.022 g/LALOGPS
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
Polarizability65.97 ųChemAxon
Number of Rings5ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon


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
MSMass Spectrum (Electron Ionization)splash10-0uxu-1000290000-e22236fe3cca8eed1ecf2021-09-05View Spectrum


Spectrum TypeDescriptionSplash KeyDeposition DateView
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-0000090000-87c1740ecd1a28f4a2d92021-09-06View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03xu-0000590000-99160b987bb7e62ab3622021-09-06View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00di-0000900000-f2d9118441a9c8c47d792021-09-06View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03dj-0000090000-d428ac6dc2fc4794cc412021-09-07View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0j4j-0000090000-2b065966ec57bb97d5112021-09-07View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0uk9-1000970000-b435817e4dc349e65ab32021-09-07View Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane (predicted from logP)
  • Mitochondria
Biospecimen Locations
  • Blood
Tissue Locations
  • Adipose Tissue
  • Adrenal Medulla
  • Bladder
  • Epidermis
  • Erythrocyte
  • Fibroblasts
  • Intestine
  • Kidney
  • Leukocyte
  • Liver
  • Platelet
  • Spleen
  • Testis
  • Thyroid Gland
Normal Concentrations
BloodDetected and Quantified0.66 +/- 0.18 uMAdult (>18 years old)FemaleNormal
    • Geigy Scientific ...
BloodDetected and Quantified0.53 +/- 0.13 uMAdult (>18 years old)MaleNormal
    • Geigy Scientific ...
BloodDetected and Quantified1.09 +/- 0.57 uMNewborn (0-30 days old)BothNormal
    • Geigy Scientific ...
Abnormal Concentrations
BloodDetected and Quantified0-1.244 uMAdult (>18 years old)MaleProtoporphyria, Erythropoietic details
Associated Disorders and Diseases
Disease References
Protoporphyria, Erythropoietic
  1. MAGNUS IA, JARRETT A, PRANKERD TA, RIMINGTON C: Erythropoietic protoporphyria. A new porphyria syndrome with solar urticaria due to protoporphyrinaemia. Lancet. 1961 Aug 26;2(7200):448-51. [PubMed:13765301 ]
Associated OMIM IDs
  • 177000 (Protoporphyria, Erythropoietic)
DrugBank IDDB02285
Phenol Explorer Compound IDNot Available
FooDB IDFDB004277
KNApSAcK IDC00007370
Chemspider ID10469486
KEGG Compound IDC02191
BiGG IDNot Available
Wikipedia LinkProtoporphyrin_IX
METLIN IDNot Available
PubChem CompoundNot Available
PDB IDNot Available
ChEBI ID15430
Food Biomarker OntologyNot Available
MarkerDB IDNot Available
Synthesis ReferenceGames, David E.; Jackson, Anthony H.; Jackson, J. Richard; Belcher, Roderick V.; Smith, Sydney G. Biosynthesis of protoporphyrin-IX from coproporphyrinogen-III. Journal of the Chemical Society, Chemical Communications (1976), (6), 187-8.
Material Safety Data Sheet (MSDS)Download (PDF)
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. [PubMed: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. [PubMed:3763462 ]
  3. Stankiewicz A: [Erythrocyte protoporphyrin IX in occupational exposure to asbestos]. Med Pr. 1984;35(5):351-4. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:10699294 ]
  21. Winkelman JW, Collins GH: Neurotoxicity of tetraphenylporphinesulfonate TPPS4 and its relation to photodynamic therapy. Photochem Photobiol. 1987 Nov;46(5):801-7. [PubMed:3441503 ]


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:
Uniprot ID:
Molecular weight:
General function:
Involved in catalytic activity
Specific function:
Catalyzes the 6-electron oxidation of protoporphyrinogen-IX to form protoporphyrin-IX.
Gene Name:
Uniprot ID:
Molecular weight:
Protoporphyrinogen IX + Oxygen → Protoporphyrin IX + Hydrogen peroxidedetails
Protoporphyrinogen IX + Oxygen → Protoporphyrin IX + Hydrogen peroxidedetails
General function:
Involved in ferrochelatase activity
Specific function:
Catalyzes the ferrous insertion into protoporphyrin IX.
Gene Name:
Uniprot ID:
Molecular weight:
Heme + Hydrogen Ion → Protoporphyrin IX + Fe2+details
Protoporphyrin IX + Fe2+ → Heme + Hydrogen Iondetails
General function:
Involved in oxidoreductase activity
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
Gene Name:
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  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed: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. [PubMed: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. [PubMed:10592235 ]
General function:
Involved in ferrochelatase activity
Specific function:
Catalyzes the ferrous insertion into protoporphyrin IX
Gene Name:
Not Available
Uniprot ID:
Molecular weight:
General function:
Involved in ferrochelatase activity
Specific function:
Catalyzes the ferrous insertion into protoporphyrin IX
Gene Name:
Not Available
Uniprot ID:
Molecular weight:
General function:
Involved in ferrochelatase activity
Specific function:
Catalyzes the ferrous insertion into protoporphyrin IX
Gene Name:
Uniprot ID:
Molecular weight: