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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Effect of myricetin and other flavonoids on the liver plasma membrane Ca2+ pump. Kinetics and structure-function relationships.

Thirty-three different flavonoids were screened for their ability to influence ATP-dependent Ca2+ uptake by rat liver plasma membrane vesicles. Nine of the flavonoids, at a concentration of 100 microM inhibited Ca2+ uptake by more than 20%. The remaining 24 flavonoids exhibited little or no effect. The relative order of potency of the more biologically active flavonoids was myricetin greater than butein greater than phloretin = luteolin greater than eriodictyol = silybin. Myricitrin and phloridzin, the glycosides of myricetin and phloretin, respectively, had no effect. The degree of inhibition caused by myricetin was concentration dependent and was also affected by the preincubation time. After 10 min of preincubation, 52 microM myricetin lowered the initial rate of 45Ca uptake by 50%. The inhibition by myricetin was non-competitive with respect to Mg-ATP and of a mixed type with respect to Ca2+. At a concentration of 100 microM, myricetin had no effect on several plasma membrane enzymes such as 5'-nucleotidase, alkaline phosphatase and a Ca2(+)-activated ATPase but inhibited K(+)-dependent p-nitrophenyl phosphatase by 83%. The ATP-dependent Ca2+ transport systems located on the plasma membrane or endoplasmic reticulum derived from other tissues were also inhibited by myricetin. Analysis of the structure-activity relationship revealed that lipid solubility and polyhydroxylation particularly at positions 5,7,3' and 4' of the flavonoid ring structure enhanced the ability of the flavonoid to inhibit Ca2+ uptake. The results suggest that inhibition of Ca2+ transport activity probably involves the interaction of the phenolic groups of the flavonoid with the Ca2+ transporting protein.[1]

References

  1. Effect of myricetin and other flavonoids on the liver plasma membrane Ca2+ pump. Kinetics and structure-function relationships. Thiyagarajah, P., Kuttan, S.C., Lim, S.C., Teo, T.S., Das, N.P. Biochem. Pharmacol. (1991) [Pubmed]
 
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