Benzo(a)pyrene metabolism (WP696)

Benzene metabolism primarily takes place in the liver, to a variety of products that are transported to the bone marrow where additional metabolism occurs. Several metabolites of benzene are responsible for the toxic effects of benzene including reactive metabolites that covalently bind macromolecules and induce oxidative damage. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP696 CPTAC Assay Portal]
last edited

Authors

Pieter Giesbertz, Thomas, MaintBot, MartijnVanIersel, Christine Chichester, Egonw, Mkutmon, AlexanderPico, and Khanspers

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: benzo(a)pyrene metabolic pathway cellular detoxification pathway xenobiotics biodegradation pathway

Participants

Label Type Compact Identifier
9-hydroxy-benzo[a]pyrene Metabolite None
Benzo[a]pyrene-9-sulfate Metabolite pubchem.compound:149850
CYP3A4 GeneProduct ensembl:ENSG00000160868
AKR1C2 GeneProduct ensembl:ENSG00000151632
AKR1C3 GeneProduct ensembl:ENSG00000196139
7,8-dihydroxy-7,8-dihydro-benzo[a]pyrene Metabolite chemspider:24123
CYP1A1 GeneProduct ensembl:ENSG00000140465
Benzo[a]pyrene-7,8-dione Metabolite pubchem.compound:105020
SULT GeneProduct None
Benzo[a]pyrene Metabolite pubchem.compound:2336
AKR1A1 GeneProduct ensembl:ENSG00000117448
Benzo[a]pyrene-6,12-dione Metabolite None
EPHX1 GeneProduct ensembl:ENSG00000143819
AKR1C4 GeneProduct ensembl:ENSG00000198610
Benzo[a]pyrene radical cation Metabolite None
3-hydroxy-benzo[a]pyrene Metabolite None
7-hydroxy-benzo[a]pyrene Metabolite None
Benzo[a]pyrene-3,6-dione Metabolite None
Benzo[a]pyrene-7-glucuronide Metabolite None
CYP1A1 GeneProduct ensembl:ENSG00000140465
Benzo[a]pyrene-7-sulfate Metabolite pubchem.compound:23703977
AKR1C1 GeneProduct ensembl:ENSG00000187134
CYP1B1 GeneProduct ensembl:ENSG00000138061
Benzo[a]pyrene-9-glucuronide Metabolite None
CYP1B1 GeneProduct ensembl:ENSG00000138061
9,10-epoxy-7,8-dihydroxy-7,8-dihydro-benzo[a]pyrene Metabolite chemspider:46738
6-hydroxy-benzo[a]pyrene Metabolite None
Cytochrome P450 peroxidase GeneProduct None
Glucuronosyltransferase GeneProduct None
7,8-epoxy-benzo[a]pyrene Metabolite None
Benzo[a]pyrene-1,6-dione Metabolite pubchem.compound:18300

References

  1. Malejka-Giganti D, Ritter CL. Peroxidative metabolism of carcinogenic N-arylhydroxamic acids: implications for tumorigenesis. Environ Health Perspect. 1994 Oct;102 Suppl 6(Suppl 6):75–81. PubMed Europe PMC Scholia
  2. Snyder R, Hedli CC. An overview of benzene metabolism. Environ Health Perspect. 1996 Dec;104 Suppl 6(Suppl 6):1165–71. PubMed Europe PMC Scholia
  3. Kisselev P, Schwarz D, Platt K-L, Schunck W-H, Roots I. Epoxidation of benzo[a]pyrene-7,8-dihydrodiol by human CYP1A1 in reconstituted membranes. Effects of charge and nonbilayer phase propensity of the membrane. Eur J Biochem. 2002 Apr;269(7):1799–805. PubMed Europe PMC Scholia
  4. Boysen G, Hecht SS. Analysis of DNA and protein adducts of benzo[a]pyrene in human tissues using structure-specific methods. Mutat Res. 2003 Jan;543(1):17–30. PubMed Europe PMC Scholia
  5. Luch A. Nature and nurture - lessons from chemical carcinogenesis. Nat Rev Cancer. 2005 Feb;5(2):113–25. PubMed Europe PMC Scholia
  6. Jin Y, Penning TM. Aldo-keto reductases and bioactivation/detoxication. Annu Rev Pharmacol Toxicol. 2007;47:263–92. PubMed Europe PMC Scholia
  7. Jiang H, Gelhaus SL, Mangal D, Harvey RG, Blair IA, Penning TM. Metabolism of benzo[a]pyrene in human bronchoalveolar H358 cells using liquid chromatography-mass spectrometry. Chem Res Toxicol. 2007 Sep;20(9):1331–41. PubMed Europe PMC Scholia