Biomaterial Database

Aflatoxin B1 epoxidation catalysed by partially purified human liver lipoxygenase. 1997

S K Roy, and A P Kulkarni

Florida Toxicology Research Center, Department of Environmental and Occupational Health, College of Public Health, University of South Florida, Tampa 33612-3805, USA.

(1) This study demonstrates for the first time the human liver lipoxygenase-mediated co-oxidation of aflatoxin B1 to the reactive metabolite, aflatoxin B1-8,9-epoxide, which rapidly hydrolyzes to dihydrodiol and preferentially binds to Tris. (2) The Tris-diol complex formed was quantitated fluorimetrically, based on its characteristic excitation at lambda ex = 395 nm and emission at lambda em = 435 nm. (3) The incubation of partially purified human liver lipoxygenase for 30 min under optimum assay conditions (3.5 mM linoleic acid and 50 microM aflatoxin B1 in Tris buffer at pH 7.2) resulted in the formation of 10.6 +/- 1.7 nmol Tris-diol/mg protein. (4) In addition to linoleic acid, other unsaturated fatty acids namely gamma-linolenic acid, cis-11, 14-eicosadienoic acid and arachidonic acid also supported the lipoxygenase mediated epoxidation of aflatoxin B1. (5) The enzymatic Tris-diol formation was significantly inhibited by all the lipoxygenase inhibitors tested in a concentration-dependent manner. (6) These results strongly suggest that lipoxygenase is capable of aflatoxin B1 metabolism and this may represent yet another pathway for the bioactivation of this hepatocarcinogen in the human liver.

UI	MeSH Term	Description	Entries
D008084	Lipoxygenase	An enzyme of the oxidoreductase class primarily found in PLANTS. It catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives.	Lipoxidase,Linoleate-Oxygen Oxidoreductase,Lipoxygenase-1,Lipoxygenase-2,Linoleate Oxygen Oxidoreductase,Lipoxygenase 1,Lipoxygenase 2,Oxidoreductase, Linoleate-Oxygen
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D009637	Masoprocol	A potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. The compound also inhibits formyltetrahydrofolate synthetase, carboxylesterase, and cyclooxygenase to a lesser extent. It also serves as an antioxidant in fats and oils.	Nordihydroguaiaretic Acid,(R,S)-4,4'-(2,3-Dimethylbutane-1,4-diyl)bispyrocatechol,Actinex,Dihydronorguaiaretic Acid,Nordihydroguaiaretic Acid, (R,S)-Isomer,meso-Nordihydroguaiaretic Acid,Acid, meso-Nordihydroguaiaretic,meso Nordihydroguaiaretic Acid
D002273	Carcinogens	Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.	Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D002384	Catalysis	The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.	Catalyses
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016604	Aflatoxin B1	A potent hepatotoxic and hepatocarcinogenic mycotoxin produced by the Aspergillus flavus group of fungi. It is also mutagenic, teratogenic, and causes immunosuppression in animals. It is found as a contaminant in peanuts, cottonseed meal, corn, and other grains. The mycotoxin requires epoxidation to aflatoxin B1 2,3-oxide for activation. Microsomal monooxygenases biotransform the toxin to the less toxic metabolites aflatoxin M1 and Q1.	Aflatoxin B(1),Aflatoxin B,Aflatoxin B1 Dihydrochloride, (6aR-cis)-Isomer,Aflatoxin B1, (6aR-cis)-Isomer, 14C-Labeled,Aflatoxin B1, (6aR-cis)-Isomer, 2H-Labeled,Aflatoxin B1, (6aR-cis)-Isomer, 3H-Labeled,Aflatoxin B1, cis(+,-)-Isomer,HSDB-3453,NSC-529592,HSDB 3453,HSDB3453,NSC 529592,NSC529592
D016859	Lipoxygenase Inhibitors	Compounds that bind to and inhibit that enzymatic activity of LIPOXYGENASES. Included under this category are inhibitors that are specific for lipoxygenase subtypes and act to reduce the production of LEUKOTRIENES.	5-Lipoxygenase Inhibitor,Lipoxygenase Inhibitor,12-Lipoxygenase Inhibitors,15-Lipoxygenase Inhibitors,5-Lipoxygenase Inhibitors,Arachidonate 12-Lipoxygenase Inhibitors,Arachidonate 15-Lipoxygenase Inhibitors,Arachidonate 5-Lipoxygenase Inhibitors,Inhibitors, Lipoxygenase,12 Lipoxygenase Inhibitors,12-Lipoxygenase Inhibitors, Arachidonate,15 Lipoxygenase Inhibitors,15-Lipoxygenase Inhibitors, Arachidonate,5 Lipoxygenase Inhibitor,5 Lipoxygenase Inhibitors,5-Lipoxygenase Inhibitors, Arachidonate,Arachidonate 12 Lipoxygenase Inhibitors,Arachidonate 15 Lipoxygenase Inhibitors,Arachidonate 5 Lipoxygenase Inhibitors,Inhibitor, 5-Lipoxygenase,Inhibitor, Lipoxygenase,Inhibitors, 12-Lipoxygenase,Inhibitors, 15-Lipoxygenase,Inhibitors, 5-Lipoxygenase,Inhibitors, Arachidonate 12-Lipoxygenase,Inhibitors, Arachidonate 15-Lipoxygenase,Inhibitors, Arachidonate 5-Lipoxygenase