Epigallocatechin-3-gallate is an inhibitor of Na+,K+-ATPase by favoring the E1 conformation

Abstract Four catechins, epigallocatechin-3-gallate, epigallocatechin, epicatechin-3-gallate, and epicatechin, inhibited activity of the Na + ,K + -ATPase. The two galloyl-type catechins were more potent inhibitors, with IC 50 values of about 1 μM, than were the other two catechins. Inhibition by epigallocatechin-3-gallate was noncompetitive with respect to ATP. Epigallocatechin-3-gallate reduced the affinity of vanadate, shifted the equilibrium of E 1 P and E 2 P toward E 1 P, and reduced the rate of the E 1 P to E 2 P transition. Epigallocatechin-3-gallate potently inhibited membrane-embedded P-type ATPases (gastric H + ,K + -ATPase and sarcoplasmic reticulum Ca 2+ -ATPase) as well as the Na + ,K + -ATPase, whereas soluble ATPases (bacterial F 1 -ATPase and myosin ATPase) were weakly inhibited. Solubilization of the Na + ,K + -ATPase with a nonionic detergent reduced sensitivity to epigallocatechin-3-gallate with an elevation of IC 50 to 10 μM. These results suggest that epigallocatechin-3-gallate exerts its inhibitory effect through interaction with plasma membrane phospholipid.