BACKGROUND: Inhibition studies on PON1 as an organophosphate-hydrolyzing and atheroprotective enzyme could be useful in elucidating the function of PON1. This study is aimed at examining the in vitro effects of the flavonoid naringenin on PON1 activity in human serum and purified enzyme. METHODS: The inhibition kinetics of the interaction of naringenin with human PON1 in serum and purified enzyme was determined spectrophotometrically using paraoxon and phenylacetate as the substrates. RESULTS: Naringenin could be introduced as an effective inhibitor on purified human PON1 activity for phenylacetate as the substrate with an IC(50) value of 10 µM. Paraoxonase and arylesterase activities of PON1, in the serum assay, were also inhibited by naringenin with IC(50) values of 37.9 and 34.6 µM, respectively. PON1, according to acompetitive-type inhibition pattern, was inhibited by naringenin with K(i) constant of 14.5 µM for serum paraoxonase activity. The results were compared with a known inhibitor of PON1, 2-hydroxyquinoline. We believe (to our knowledge) that this is the first reported study for kinetic parameters of PON1 inhibition by naringenin. CONCLUSIONS: Lipophilic property appears to be an important feature of the structure in evaluating the inhibitor potential. Comparison of our findings and other authors showed that the induction of PON1 gene by naringenin and its inhibitory effects on the enzyme protein are probably two different mechanisms by which the flavonoid affects PON1. The in vitro data reported in this study could be useful in the development of structure-activity relationship for PON1 inhibition.
BACKGROUND: Inhibition studies on PON1 as an organophosphate-hydrolyzing and atheroprotective enzyme could be useful in elucidating the function of PON1. This study is aimed at examining the in vitro effects of the flavonoidnaringenin on PON1 activity in human serum and purified enzyme. METHODS: The inhibition kinetics of the interaction of naringenin with humanPON1 in serum and purified enzyme was determined spectrophotometrically using paraoxon and phenylacetate as the substrates. RESULTS:Naringenin could be introduced as an effective inhibitor on purified humanPON1 activity for phenylacetate as the substrate with an IC(50) value of 10 µM. Paraoxonase and arylesterase activities of PON1, in the serum assay, were also inhibited by naringenin with IC(50) values of 37.9 and 34.6 µM, respectively. PON1, according to acompetitive-type inhibition pattern, was inhibited by naringenin with K(i) constant of 14.5 µM for serum paraoxonase activity. The results were compared with a known inhibitor of PON1, 2-hydroxyquinoline. We believe (to our knowledge) that this is the first reported study for kinetic parameters of PON1 inhibition by naringenin. CONCLUSIONS: Lipophilic property appears to be an important feature of the structure in evaluating the inhibitor potential. Comparison of our findings and other authors showed that the induction of PON1 gene by naringenin and its inhibitory effects on the enzyme protein are probably two different mechanisms by which the flavonoid affects PON1. The in vitro data reported in this study could be useful in the development of structure-activity relationship for PON1 inhibition.
Authors: Rakesh S Bargota; Mahmoud Akhtar; Keith Biggadike; David Gani; Rudolf K Allemann Journal: Bioorg Med Chem Lett Date: 2003-05-19 Impact factor: 2.823
Authors: Michal Harel; Amir Aharoni; Leonid Gaidukov; Boris Brumshtein; Olga Khersonsky; Ran Meged; Hay Dvir; Raimond B G Ravelli; Andrew McCarthy; Lilly Toker; Israel Silman; Joel L Sussman; Dan S Tawfik Journal: Nat Struct Mol Biol Date: 2004-04-18 Impact factor: 15.369
Authors: Charlotte Schrader; Insa M A Ernst; Heike Sinnecker; Sebastian T Soukup; Sabine E Kulling; Gerald Rimbach Journal: J Cell Mol Med Date: 2012-10 Impact factor: 5.310