Flavonoids enzyme inhibition

Effects of Allelochemlcals on ATPases. Several flavonoid compounds inhibit ATPase activity that is associated with mineral absorption. Phloretin and quercetin (100 pM) inhibited the plasma membrane ATPase Isolated from oat roots (33). The naphthoquinone juglone was inhibitory also. However, neither ferulic acid nor salicylic acid inhibited the ATPase. Additional research has shown that even at 10 mM salicylic acid inhibits ATPase activity only 10-15% (49). This lack of activity by salicylic acid was substantiated with the plasma membrane ATPase Isolated from Neurospora crassa (50) however, the flavonols fisetln, morin, myricetin, quercetin, and rutin were inhibitory to the Neurospora ATPase. Flavonoids inhibited the transport ATPases of several animal systems also (51-53). Thus, it appears that flavonoids but not phenolic acids might affect mineral transport by inhibiting ATPase enzymes. 

The ability of flavonoids (quercetin and rutin) to react with superoxide has been shown in both aqueous and aprotic media [59,94]. Then, the inhibitory activity of flavonoids in various enzymatic and nonenzymatic superoxide-producing systems has been studied. It was found that flavonoids may inhibit superoxide production by xanthine oxidase by both the scavenging of superoxide and the inhibition of enzyme activity, with the ratio of these two mechanisms depending on the structures of flavonoids (Table 29.4). As seen from Table 29.4, the data obtained by different authors may significantly differ. For example, in recent work [107] it was found that rutin was ineffective in the inhibition of xanthine oxidase that contradicts the previous results [108,109], The origins of such big differences are unknown. 

Flavonoids, as food components or potential drugs, interact with a wide range of proteins by distinct mechanisms weak and rather unspecific binding of tannins to proline-rich or histi-dine-rich random coils leading to protein precipitation, specific enzyme inhibition, and... 

Selected naturally occurring flavonoids have been shown to inhibit three reverse transcriptases (RT) (avian myeloblastosis RT, Rous-associated virus-2 RT, and Moloney murine leukemia virus, or MMLV, RT) when poly(rA)oligo(dT) 12-18 or rabbit globin mRNA was used as a template. Amentoflavone, scutellarein, and quercetin were the most active compounds, and their effect was concentration dependent. The enzymes exhibited differential sensitivity to the inhibitory effects of the flavonoids. These flavonoids also inhibited rabbit globin mRNA-directed MMLV RT-catalyzed... 

Inhibition by 7-hydroxyflavone was competitive with respect to the substrate androstenedione. Flavonoids of the 5,7-dihydroxyflavone series could bind to the active site human cytochrome P-450 aromatase with affinity. The flavonoid kaempferol inhibited aromatase enzyme activity competitively in a human Glyoxalase cell culture system. Such results suggest that diets rich in these compounds could contribute to the control of estrogen-dependent conditions, such as breast cancer. 

Schubert, S.Y., Lansky, E.P., and Neeman, I., Antioxidant and eicosanoid enzyme inhibition properties of pomegranate seed oil and fermented juice flavonoids, J. Ethnopharmacol., 66, 11, 1999. 

Since both cyclooxygenase and lipoxygenase catalyze stereospecific free radical peroxidations of arachidonic acid at their active sites, it is widely believed that the dual COX and LOX inhibition activities of flavonoids derive from their non-selective free radical scavenging or iron chelating functions rather than specific enzyme inhibition. However, Laughton et al. 

Most microorganisms possess only a single KAR, and several authors have pointed out these enzymes are therefore potentially good targets for drug discovery. It is consequently surprising that potent inhibitors of this enzyme class have not been reported so far. Tasdemir et alJ have identified several flavonoids that inhibit the... 

The antioxidant actions of flavonoids appear to be involved in their observed antithrombotic action [50-52]. The antithrombotic and vasoprotective actions of quercetin, rutin, and other flavonoids have been attributed to their ability to bind to platelet membranes and scavenge free radicals [50]. In this manner, flavonoids restore the biosynthesis and action of endothelial prostacyclin and endothelialderived relaxing factor (EDRF), both of which are known to be inhibited by free radicals [50, 53, 54]. However, some flavonoids may inhibit arachidonic acid metabolism and platelet function by flavonoid-enzyme interactions rather than by antioxidant effects [55]. In addition to their antiaggregatory effects, flavonoids appear to increase vasodilation by inducing vascular smooth muscle relaxation, which may be mediated by inhibition of protein kinase C, PDFs, or by decreased cellular uptake of calcium [56]. 

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