title: Trapping of phenylacetaldehyde as a key mechanism responsible for naringenin's inhibitory activity in mutagenic 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine formation.
abstract: Chemical model reactions were carried out to investigate the mechanism of inhibition by a citrus flavonoid, naringenin, on the formation of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), the most abundant mutagenic heterocyclic amine found in foods. GC-MS showed that naringenin dose dependently reduced the level of phenylacetaldehyde, a key intermediate on the pathway to the formation of PhIP. Subsequent LC-MS analyses of samples from a wide range of model systems consisting of PhIP precursors, including phenylalanine, glucose, and creatinine, suggested that naringenin scavenged phenylacetaldehyde via adduct formation. An isotope-labeling study showed that the postulated adducts contain fragment(s) of phenylalanine origin. Direct reaction employing phenylacetaldehyde and naringenin further confirmed the capability of naringenin to form adducts with phenylacetaldehyde, thus reducing its availability for PhIP formation. Two of the adducts were subsequently isolated and purified. Their structure was elucidated by one- and two-dimensional NMR spectroscopy as 8- C-( E-phenylethenyl)naringenin (1) and 6- C-( E-phenylethenyl)naringenin (2), respectively, suggesting that C-6 and C-8 are two of the active sites of naringenin in adduct formation. These two adducts were also identified from thermally processed beef models, highlighting phenylacetaldehyde trapping as a key mechanism of naringenin to inhibit PhIP formation.
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong 123456, People's Republic of China.
authors.forename: Ka-Wing
authors.initials: KW
authors.lastname: Cheng
authors.forename: Chi Chun
authors.initials: CC
authors.lastname: Wong
authors.forename: Chi Kong
authors.initials: CK
authors.lastname: Cho
authors.forename: Ivan K
authors.initials: IK
authors.lastname: Chu
authors.forename: Kong Hung
authors.initials: KH
authors.lastname: Sze
authors.forename: Clive
authors.initials: C
authors.lastname: Lo
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Mingfu
authors.initials: M
authors.lastname: Wang
mesh_terms: D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000737:chemistry; D000818:Animals; D002417:Cattle; D044950:Flavanones / Q000494:pharmacology*; D007093:Imidazoles / Q000737:chemistry* / Q000378:metabolism; D013058:Mass Spectrometry; D008460:Meat; D008954:Models, Biological; D015394:Molecular Structure; D016296:Mutagenesis / Q000187:drug effects*
chemical_list: D044950:Flavanones; D007093:Imidazoles; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D000079:Acetaldehyde; C005273:naringenin; C013192:phenylacetaldehyde