Reactome | CYP3A4,5 oxidise AFB1 to AFXBO

CYP3A4,5 oxidise AFB1 to AFXBO

Stable Identifier

R-HSA-213175

Type

Reaction

Species

Homo sapiens

Compartment

endoplasmic reticulum membrane, endoplasmic reticulum lumen

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Aflatoxins are produced by the fungal molds Aspergillus flavus and Aspergillus parasiticus. Dietary contamination accounts for adverse health problems including liver cancer therby classifying aflatoxins as Group 1 carcinogens in humans. The B1 form of aflatoxin (AFB1) is especially carcinogenic in a number of species including humans.
AFB1 requires microsomal oxidation to produce epoxides which are the cause of their toxic and carcinogenic effects. In humans, both CYP3A4 and CYP3A5 are able to produce epoxide stereoisomers of AFB1, the most potent being aflatoxin B1 exo-8,9-oxide (AFXBO) (Gallagher et al. 1996).

Literature References

PubMed ID	Title	Journal	Year
8975785	The kinetics of aflatoxin B1 oxidation by human cDNA-expressed and human liver microsomal cytochromes P450 1A2 and 3A4 Eaton, DL, Stapleton, PL, Kunze, KL, Gallagher, EP	Toxicol. Appl. Pharmacol.	1996
15454734	Increased levels of aflatoxin-albumin adducts are associated with CYP3A5 polymorphisms in The Gambia, West Africa Kirk, G, Mendy, M, Hustert, E, Whittle, HC, Pedersen, B, Brockmöller, J, Wild, CP, Wojnowski, L, Turner, PC	Pharmacogenetics	2004