Porphobilinogen

Basic Info

Common NamePorphobilinogen(F05313)
2D Structure
Description

Porphobilinogen is a pyrrole involved in porphyrin metabolism. It consists of a pyrrole ring with acetyl, propionyl, and aminomethyl side chains; It is a key monopyrrolic intermediate in porphyrin, chlorophyll and vitamin B12 biosynthesis. Porphobilinogen is generated by the enzyme ALA dehydratase by combining two molecules of dALA together, and converted into hydroxymethyl bilane by the enzyme porphobilinogen deaminase. 4 molecules of porphobilinogen are condensed to form one molecule of uroporphyrinogen III, which is then converted successively to coproporphyrinogen III, protoporphyrin IX, and heme. Porphobilinogen is produced in excess and excreted in the urine in acute intermittent porphyria and several other porphyrias.

FRCD IDF05313
CAS Number487-90-1
PubChem CID1021
FormulaC10H14N2O4
IUPAC Name

3-[5-(aminomethyl)-4-(carboxymethyl)-1H-pyrrol-3-yl]propanoic acid

InChI Key

QSHWIQZFGQKFMA-UHFFFAOYSA-N

InChI

InChI=1S/C10H14N2O4/c11-4-8-7(3-10(15)16)6(5-12-8)1-2-9(13)14/h5,12H,1-4,11H2,(H,13,14)(H,15,16)

Canonical SMILES

C1=C(C(=C(N1)CN)CC(=O)O)CCC(=O)O

Isomeric SMILES

C1=C(C(=C(N1)CN)CC(=O)O)CCC(=O)O

WikipediaPorphobilinogen
Synonyms
        
            3-[5-(AMINOMETHYL)-4-(CARBOXYMETHYL)-1H-PYRROL-3-YL]PROPANOIC ACID
        
            porphobilinogen
        
            487-90-1
        
            UNII-74KHC72QXK
        
            1H-Pyrrole-3-propanoic acid, 5-(aminomethyl)-4-(carboxymethyl)-
        
            2-aminomethylpyrrol-3-acetic acid 4-propionic acid
        
            74KHC72QXK
        
            PBG
        
            CHEBI:17381
        
            5-(Aminomethyl)-4-(carboxymethyl)-1H-pyrrole-3-propanoic acid
Classifies
                

                  
                    Animal Toxin
Update DateNov 13, 2018 17:07

Chemical Taxonomy

KingdomOrganic compounds
SuperclassOrganic nitrogen compounds
ClassOrganonitrogen compounds
SubclassAmines
Intermediate Tree NodesNot available
Direct ParentAralkylamines
Alternative Parents
Molecular FrameworkAromatic heteromonocyclic compounds
SubstituentsAralkylamine - Dicarboxylic acid or derivatives - Substituted pyrrole - Heteroaromatic compound - Pyrrole - Amino acid - Amino acid or derivatives - Carboxylic acid derivative - Azacycle - Carboxylic acid - Organoheterocyclic compound - Organopnictogen compound - Primary amine - Organooxygen compound - Primary aliphatic amine - Organic oxygen compound - Hydrocarbon derivative - Carbonyl group - Organic oxide - Aromatic heteromonocyclic compound
DescriptionThis compound belongs to the class of organic compounds known as aralkylamines. These are alkylamines in which the alkyl group is substituted at one carbon atom by an aromatic hydrocarbyl group.

Properties

Property NameProperty Value
Molecular Weight226.232
Hydrogen Bond Donor Count4
Hydrogen Bond Acceptor Count5
Rotatable Bond Count6
Complexity270
Monoisotopic Mass226.095
Exact Mass226.095
XLogP-3.5
Formal Charge0
Heavy Atom Count16
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

ADMET

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.5300
Human Intestinal AbsorptionHIA+0.6694
Caco-2 PermeabilityCaco2-0.7613
P-glycoprotein SubstrateSubstrate0.6005
P-glycoprotein InhibitorNon-inhibitor0.9798
Non-inhibitor0.9936
Renal Organic Cation TransporterNon-inhibitor0.8196
Distribution
Subcellular localizationMitochondria0.5782
Metabolism
CYP450 2C9 SubstrateNon-substrate0.9040
CYP450 2D6 SubstrateNon-substrate0.7938
CYP450 3A4 SubstrateNon-substrate0.7691
CYP450 1A2 InhibitorNon-inhibitor0.8127
CYP450 2C9 InhibitorNon-inhibitor0.9560
CYP450 2D6 InhibitorNon-inhibitor0.9395
CYP450 2C19 InhibitorNon-inhibitor0.9390
CYP450 3A4 InhibitorNon-inhibitor0.9709
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.9959
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.9522
Non-inhibitor0.9012
AMES ToxicityNon AMES toxic0.8901
CarcinogensNon-carcinogens0.9420
Fish ToxicityHigh FHMT0.7521
Tetrahymena Pyriformis ToxicityHigh TPT0.8882
Honey Bee ToxicityLow HBT0.8338
BiodegradationNot ready biodegradable0.7077
Acute Oral ToxicityIII0.5914
Carcinogenicity (Three-class)Non-required0.6957
Model Value Unit
Absorption
Aqueous solubility-2.0731LogS
Caco-2 Permeability-0.2135LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity2.0559LD50, mol/kg
Fish Toxicity2.1552pLC50, mg/L
Tetrahymena Pyriformis Toxicity0.0241pIGC50, ug/L

References

TitleJournalDatePubmed ID
Effects of bisphenol A on chlorophyll synthesis in soybean seedlings.Environ Sci Pollut Res Int2015 Apr25352395
Effects of Lead Exposure and Genetic Polymorphisms on ALAD and GPx Activities in Brazilian Battery Workers.J Toxicol Environ Health A201526275098
Evaluation of toxic metals and essential elements in children with learning disabilities from a rural area of southern Brazil.Int J Environ Res Public Health2014 Oct 1725329533
Experimental manipulation of dietary lead levels in great tit nestlings: limited effects on growth, physiology and survival.Ecotoxicology2014 Jul24700183
Biochemical parameters of pregnant rats and their offspring exposed to different doses of inorganic mercury in drinking water.Food Chem Toxicol2012 Jul22580302
Delayed biochemical changes induced by mercury intoxication are prevented by zincpre-exposure.Ecotoxicol Environ Saf2011 Mar21183220
Inhibition of hepatic δ-aminolevulinate dehydratase activity induced by mercuric chloride is potentiated by N-acetylcysteine in vitro.Food Chem Toxicol2011 Jan21056077
[Acute intermittent porphyria and inappropriate ADH syndrome].Rev Esp Anestesiol Reanim2010 May20527347
Anaemia and abdominal pain due to occupational lead poisoning.Haematologica2007 Feb17405745
Effects of individual and combined exposure to sodium arsenite and sodium fluoride on tissue oxidative stress, arsenic and fluoride levels in male mice.Chem Biol Interact2006 Aug 2516828073
Therapeutic value of Hippophae rhamnoides L. against subchronic arsenic toxicity in mice.J Med Food2005 Fall16176147
2,3-Dimercapto-1-propanol does not alter the porphobilinogen synthase inhibition but decreases the mercury content in liver and kidney of suckling rats exposed to HgCl2.Basic Clin Pharmacol Toxicol2005 Apr15755313
Pro-oxidant and antioxidant factors in acute intermittent porphyria: familystudies.J Inherit Metab Dis200415159656
Possible role of metal redistribution, hepatotoxicity and oxidative stress in chelating agents induced hepatic and renal metallothionein in rats.Food Chem Toxicol2001 Oct11524141
The effect of zinc supplementation on the effects of lead on the rat testis.Reprod Toxicol1998 Sep-Oct9763245
The magnitude of lead toxicity in broiler chickens.Vet Hum Toxicol1995 Feb7709582
Lead-dithiocarbamate interaction. Effect on ALAD activity in isolated rat hepatocytes.Biol Trace Elem Res1989 Jul-Sep2484608
Effects of perinatal treatment with lead and disulfiram on ALAD activity in blood, liver and kidney and urinary ALA excretion in rats.Pharmacol Toxicol1989 Apr2748540
Increased lead uptake and inhibition of ALAD-activity in isolated rat hepatocytes incubated with lead-diethyldithiocarbamate complex.Chem Biol Interact19882844423
Measurement of enzymes in environmental intoxications.Ann Clin Lab Sci1977 May-Jun324345

Targets

Target Details

Delta-aminolevulinic acid dehydratase

General Function:
Zinc ion binding
Specific Function:
Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen.
Gene Name:
ALAD
Uniprot ID:
P13716
Molecular Weight:
36294.485 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 ]