Differential effects of flavonoids on bovine kidney low molecular mass protein tyrosine phosphatase.
Among the structurally related flavonoids tested on the bovine kidney low molecular weight protein tyrosine phosphatase (LMrPTP) activity, quercetin activated by about 2.6-fold the p-nitrophenyl-phosphate (p-NPP)-directed reaction, in contrast to morin that acted as a competitive inhibitor, with Ki values of 87, 73 and 50 microM for p-NPP, FMN, and tyrosine-phosphate, respectively. Other related flavonoids, such as rutin, kaempferol, catechin, narigin, phloretin and taxifolin did not significantly affect the LMrPTP activity. The positions of the hydroxyl groups in the structures of the flavonoids were important for their distinct effects on LMrPTP activity. The hydroxyl groups at C3' and C4' and the presence of a double bond at C2 and C3 were essential for the activating effect of quercetin. The absence of the 3'-OH (kaempferol), absence of the double bond (taxifolin) and the presence of the sugar rutinose at the 3-OH (rutin) suppressed the effect of quercetin. The C2'- and C4'-hydroxyl groups, the presence of the double bond, and a C4-ketone group were important requirements for the inhibitory effects of morin.
Miranda
Márcio A
MA
Departamento de Bioquimica, Instituto de Biologia, UNICAMP 13083-970 Campinas, São Paulo, Brazil.
Okamoto
André K
AK
Ferreira
Carmen V
CV
Silva
Thelma L
TL
Granjeiro
José M
JM
Aoyama
Hiroshi
H
D000818:Animals; D002417:Cattle; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry*; D044948:Flavonols / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D008956:Models, Chemical; D008970:Molecular Weight; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry*; D011794:Quercetin / Q000031:analogs & derivatives / Q000737:chemistry
D004791:Enzyme Inhibitors; D005419:Flavonoids; D044948:Flavonols; D011794:Quercetin; C003377:taxifolin; D017027:Protein Tyrosine Phosphatases