Flavanone

About: Flavanone is a research topic. Over the lifetime, 1965 publications have been published within this topic receiving 54729 citations. The topic is also known as: flavanones.

Isolation of potential cancer chemopreventive agents from Eriodictyon californicum.

Abstract: Activity-based fractionation of Eriodictyon californicum resulted in the isolation of 12 flavonoids that inhibit the metabolism of the carcinogen benzo[a]pyrene by hamster embryo cells in tissue culture. One was identified as a new flavanone, 3'-methyl-4'-isobutyryleriodictoyol [1], on the basis of spectroscopic analysis and alkaline hydrolysis. The seven other active flavanones were identified as eriodictyol [2], homoeriodictyol [3], 5,4'-dihydroxy-6,7-dimethoxyflavanone [4], pinocembrin [5], sakuranetin [6], 5,7,4'-trihydroxy-6,3'-dimethoxyflavanone [7], and naringenin 4'-methyl ether [8]. Four active flavones were also isolated: cirsimaritin [9], chrysoeriol [10], hispidulin [11], and chrysin [12]. The high inhibition of benzo[a]pyrene metabolism and the activation of benzo[a]pyrene to ultimate carcinogenic DNA-binding metabolites by cirsimaritin and chrysoeriol at a concentration of only 10 micrograms/ml indicates that these flavones warrant further investigation in vivo as potential chemopreventive agents.

Identification of strictly conserved histidine and arginine residues as part of the active site in Petunia hybrida flavanone 3beta-hydroxylase.

Abstract: Flavanone 3β-hydroxylase, involved in the biosynthesis of flavonoids, catechins, and anthocyanidins, is a non-heme iron enzyme, dependent on Fe2+, molecular oxygen, 2-oxoglutarate, and ascorbate, the typical cofactors of the class of 2-oxoglutarate-dependent dioxygenases. Sequence alignment analysis of various 2-oxoglutarate-dependent dioxygenases and related enzymes revealed eight amino acid residues that seem to be strictly conserved within this group of enzymes. Among these residues, two histidines (His220 and His278) and one aspartic acid (Asp222) were identified as part of the putative iron-binding site and an arginine residue (Arg288) as part of the 2-oxoglutarate binding site, by site-directed mutagenesis and functional analysis of the mutated recombinant enzyme. The mutant genes were expressed in Escherichia coli to give soluble proteins whose molecular masses were in excellent agreement with the wild-type enzyme. Four out of nine mutant enzymes, [Gln78]FHT, [Gln121]FHT, [Gln264]FHT and [Gln266]FHT, were enzymatically active with activities reduced to 26–57%, implying that the mutated amino acid residues are not essential for catalysis. Replacement of His220 by glutamine and Asp222 by asparagine remarkably reduced the catalytic activity to about 0.15% and 0.4%, respectively. The [Gln220]FHT and [Asn222]FHT enzymes showed a slightly increased Km value with respect to iron binding, as compared to the wild-type enzyme. The most drastic effect on the reaction rate of flavanone 3β-hydroxylase was achieved by mutating His278 to glutamine. The mutant had no detectable enzyme activity, indicating that His278 was essential for the catalytic reaction. The observed protection of purified enzyme from inactivation by diethylpyrocarbonate after the addition of cofactors provided further independent confirmation for the involvement of histidine residues in the active site. The substitution of Arg288 by lysine or glutamine induced a precipitous decrease in catalytic activity and a fivefold and 160-fold increase in the Michaelis constants for 2-oxoglutarate, respectively. In addition, the enzymatic activities of the latter two mutant enzymes showed a strong pH dependence in the weakly acidic as well as in the neutral pH range, unlike the wild-type enzyme. These results clearly indicate that Arg288 probably contributes to the specific binding of 2-oxoglutarate at the active site of the enzyme, most likely by providing a positive charge, properly located in order to interact with the (5-carboxyl function of 2-oxoglutarate. Furthermore, we conclude that His220, His278 and Asp222 constitute three of the possible ligands for iron binding in the active site of flavanone 3β-hydroxylase.

Concentration and Solubility of Flavanones in Orange Beverages Affect Their Bioavailability in Humans

Abstract: Orange juice is a very rich source of dietary flavanones. The effect of flavanone concentration and solubility of orange beverages on their bioavailability has been studied in a crossover study with 10 healthy volunteers. Five different beverages with different flavanone concentrations were evaluated. Commercial orange juices (29.2-70.3 mg of flavanones/100 mL) were compared with experimental orange beverages in which the flavanone concentration was enhanced (110.2 mg/100 mL). Hesperetin and naringenin glucuronides and sulfates were detected and quantified in plasma and urine. The study shows that the solubility of the flavanones, and particularly that of hesperidin, in the juice is a key factor for the bioavailability as flavanone excretion and the C(max) in plasma correlate well with the soluble flavanone concentration in the juice, whereas it has no correlation with the total flavanone intake. In addition, a large interindividual variation was observed, this being consistent for each individual after the intake of the different beverages, suggesting that flavanone bioavailability is also dependent on the occurrence of specific microbiota that is able to remove the rutinosides from the juice glycosides, which results in aglycones that are then absorbed from the gut.