What would be the impact on metabolism if the F1F0 ATP synthase required six protons moving through the a-subunit per ATP released?
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Answer:
Mitochondrial proton F0F1-ATPase/ATP synthase synthesizes ATP during oxidative phosphorylation. In this study, we examined the effects of several groups of polyphenolic phytochemicals on the activity of the enzyme.
Resveratrol, a stilbene phytoalexin that is present in grapes and red wine, concentration-dependently inhibited the enzymatic activity of both rat brain and liver F0F1-ATPase/ATP synthase (IC50 of 12–28 μm).
Screening of other polyphenolic phytochemicals using rat brain F0F1-ATPase activity resulted in the following ranking potency (IC50 in parenthesis): piceatannol (8 μm)>resveratrol (19 μm)=(−)epigallocatechin gallate (17 μm)>(−)epicatechin gallate, curcumin (45 μm)>genistein=biochanin A=quercetin=kaempferol=morin (55–65 μm)>phloretin=apigenin=daidzein (approx. 100 μm). Genistin, quercitrin, phloridzin, (+)catechin, (+)epicatechin, (−)epicatechin and (−)epigallocatechin had little effect at similar concentrations. Tannic acid, theaflavins (tea extract) and grape seed proanthocyanidin extract (GSPE) had IC50 values of 5, 20 and 30 μg ml−1, respectively. Several monophenolic antioxidants and non-phenolic compounds were ineffective at concentrations of 210 μm or higher.
The inhibition of F0F1-ATPase by resveratrol and genistein was non-competitive in nature.
The effects of polyphenolic phytochemicals were additive.
Both resveratrol and genistein had little effect on the Na+/K+-ATPase activity of porcine cerebral cortex, whereas quercetin had similar inhibitory potency as for F0F1-ATPase.
In conclusion, the ATP synthase is a target for dietary phytochemicals. This pharmacological property of these phytochemicals should be included in the examination of their health benefits as well as potential cytotoxicity.
Keywords: Phytoestrogens, F0F1-ATPase/ATP synthase, Na+/K+-ATPase, flavonoids, mitochondria, resveratrol, genistein, catechins, tea