The Experts below are selected from a list of 1782 Experts worldwide ranked by ideXlab platform
David F Grant - One of the best experts on this subject based on the ideXlab platform.
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effects of human soluble epoxide hydrolase polymorphisms on Isoprenoid Phosphate hydrolysis
Biochemical and Biophysical Research Communications, 2006Co-Authors: Ahmed Enayetallah, David F GrantAbstract:Soluble epoxide hydrolase (sEH) is highly expressed in human liver and contains a C-terminal epoxide hydrolase activity and an N-terminal phosphatase activity. Endogenous C-terminal hydrolase substrates include arachidonic acid epoxides, however, data are limited regarding possible endogenous substrates for the N-terminal phosphatase. Possible sEH N-terminal substrates include Isoprenoid Phosphate precursors of cholesterol biosynthesis and protein isoprenylation. Here, we report the kinetic analysis for a range of sEH Isoprenoid substrates. We also provide an analysis of the effects of human sEH polymorphisms on Isoprenoid hydrolysis. Interestingly, the Arg287Gln polymorphism recently suggested to be involved in hypercholesterolemia was found to possess a higher Isoprenoid phosphatase activity than the wild type sEH. Consistent with the finding of Isoprenoid Phosphates as substrates for sEH, we identified Isoprenoid-derived N-terminal inhibitors with IC50 values ranging from 0.84 (±0.9) to 55.1 (±30.7) μM. Finally, we evaluated the effects of the different Isoprenoid compounds on the C-terminal hydrolase activity.
Ahmed Enayetallah - One of the best experts on this subject based on the ideXlab platform.
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effects of human soluble epoxide hydrolase polymorphisms on Isoprenoid Phosphate hydrolysis
Biochemical and Biophysical Research Communications, 2006Co-Authors: Ahmed Enayetallah, David F GrantAbstract:Soluble epoxide hydrolase (sEH) is highly expressed in human liver and contains a C-terminal epoxide hydrolase activity and an N-terminal phosphatase activity. Endogenous C-terminal hydrolase substrates include arachidonic acid epoxides, however, data are limited regarding possible endogenous substrates for the N-terminal phosphatase. Possible sEH N-terminal substrates include Isoprenoid Phosphate precursors of cholesterol biosynthesis and protein isoprenylation. Here, we report the kinetic analysis for a range of sEH Isoprenoid substrates. We also provide an analysis of the effects of human sEH polymorphisms on Isoprenoid hydrolysis. Interestingly, the Arg287Gln polymorphism recently suggested to be involved in hypercholesterolemia was found to possess a higher Isoprenoid phosphatase activity than the wild type sEH. Consistent with the finding of Isoprenoid Phosphates as substrates for sEH, we identified Isoprenoid-derived N-terminal inhibitors with IC50 values ranging from 0.84 (±0.9) to 55.1 (±30.7) μM. Finally, we evaluated the effects of the different Isoprenoid compounds on the C-terminal hydrolase activity.
Paul C Sternweis - One of the best experts on this subject based on the ideXlab platform.
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the lpp1 and dpp1 gene products account for most of the Isoprenoid Phosphate phosphatase activities in saccharomyces cerevisiae
Journal of Biological Chemistry, 1999Co-Authors: Alexander J Faulkner, Xiaoming Chen, Jeffrey S Rush, Bruce F Horazdovsky, Charles J Waechter, George M Carman, Paul C SternweisAbstract:Abstract Two genes in Saccharomyces cerevisiae, LPP1 and DPP1, with homology to a mammalian phosphatidic acid (PA) phosphatase were identified and disrupted. Neither single nor combined deletions resulted in growth or secretion phenotypes. As observed previously (Toke, D. A., Bennett, W. L., Dillon, D. A., Wu, W.-I., Chen, X., Ostrander, D. B., Oshiro, J., Cremesti, A., Voelker, D. R., Fischl, A. S., and Carman, G. M. (1998) J. Biol. Chem. 273, 3278–3284; Toke, D. A., Bennett, W. L., Oshiro, J., Wu, W.-I., Voelker, D. R., and Carman, G. M. (1998) J. Biol. Chem. 273, 14331–14338), the disruption of DPP1 and LPP1 produced profound losses of Mg2+-independent PA phosphatase activity. The coincident attenuation of hydrolytic activity against diacylglycerol pyroPhosphate prompted an examination of the effects of these disruptions on hydrolysis of Isoprenoid pyroPhosphates. Disruption of either LPP1 or DPP1 caused respective decreases of about 25 and 75% in Mg2+-independent hydrolysis of several Isoprenoid Phosphates by particulate fractions isolated from these cells. The particulate and cytosolic fractions from the double disruption (lpp1Δ dpp1Δ) showed essentially complete loss of Mg2+-independent hydrolytic activity toward dolichyl Phosphate (dolichyl-P), dolichyl pyroPhosphate (dolichyl-P-P), farnesyl pyroPhosphate (farnesyl-P-P), and geranylgeranyl pyroPhosphate (geranylgeranyl-P-P). However, a modest Mg2+-stimulated activity toward PA and dolichyl-P was retained in cytosol fromlpp1Δ dpp1Δ cells. The action of Dpp1p on isoprenyl pyroPhosphates was confirmed by characterization of the hydrolysis of geranylgeranyl-P-P by the purified protein. These results indicate that LPP1 and DPP1 account for most of the hydrolytic activities toward dolichyl-P-P, dolichyl-P, farnesyl-P-P, and geranylgeranyl-P-P but also suggest that yeast contain other enzymes capable of dephosphorylating these essential Isoprenoid intermediates.
Xiaoming Chen - One of the best experts on this subject based on the ideXlab platform.
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the lpp1 and dpp1 gene products account for most of the Isoprenoid Phosphate phosphatase activities in saccharomyces cerevisiae
Journal of Biological Chemistry, 1999Co-Authors: Alexander J Faulkner, Xiaoming Chen, Jeffrey S Rush, Bruce F Horazdovsky, Charles J Waechter, George M Carman, Paul C SternweisAbstract:Abstract Two genes in Saccharomyces cerevisiae, LPP1 and DPP1, with homology to a mammalian phosphatidic acid (PA) phosphatase were identified and disrupted. Neither single nor combined deletions resulted in growth or secretion phenotypes. As observed previously (Toke, D. A., Bennett, W. L., Dillon, D. A., Wu, W.-I., Chen, X., Ostrander, D. B., Oshiro, J., Cremesti, A., Voelker, D. R., Fischl, A. S., and Carman, G. M. (1998) J. Biol. Chem. 273, 3278–3284; Toke, D. A., Bennett, W. L., Oshiro, J., Wu, W.-I., Voelker, D. R., and Carman, G. M. (1998) J. Biol. Chem. 273, 14331–14338), the disruption of DPP1 and LPP1 produced profound losses of Mg2+-independent PA phosphatase activity. The coincident attenuation of hydrolytic activity against diacylglycerol pyroPhosphate prompted an examination of the effects of these disruptions on hydrolysis of Isoprenoid pyroPhosphates. Disruption of either LPP1 or DPP1 caused respective decreases of about 25 and 75% in Mg2+-independent hydrolysis of several Isoprenoid Phosphates by particulate fractions isolated from these cells. The particulate and cytosolic fractions from the double disruption (lpp1Δ dpp1Δ) showed essentially complete loss of Mg2+-independent hydrolytic activity toward dolichyl Phosphate (dolichyl-P), dolichyl pyroPhosphate (dolichyl-P-P), farnesyl pyroPhosphate (farnesyl-P-P), and geranylgeranyl pyroPhosphate (geranylgeranyl-P-P). However, a modest Mg2+-stimulated activity toward PA and dolichyl-P was retained in cytosol fromlpp1Δ dpp1Δ cells. The action of Dpp1p on isoprenyl pyroPhosphates was confirmed by characterization of the hydrolysis of geranylgeranyl-P-P by the purified protein. These results indicate that LPP1 and DPP1 account for most of the hydrolytic activities toward dolichyl-P-P, dolichyl-P, farnesyl-P-P, and geranylgeranyl-P-P but also suggest that yeast contain other enzymes capable of dephosphorylating these essential Isoprenoid intermediates.
Alexander J Faulkner - One of the best experts on this subject based on the ideXlab platform.
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the lpp1 and dpp1 gene products account for most of the Isoprenoid Phosphate phosphatase activities in saccharomyces cerevisiae
Journal of Biological Chemistry, 1999Co-Authors: Alexander J Faulkner, Xiaoming Chen, Jeffrey S Rush, Bruce F Horazdovsky, Charles J Waechter, George M Carman, Paul C SternweisAbstract:Abstract Two genes in Saccharomyces cerevisiae, LPP1 and DPP1, with homology to a mammalian phosphatidic acid (PA) phosphatase were identified and disrupted. Neither single nor combined deletions resulted in growth or secretion phenotypes. As observed previously (Toke, D. A., Bennett, W. L., Dillon, D. A., Wu, W.-I., Chen, X., Ostrander, D. B., Oshiro, J., Cremesti, A., Voelker, D. R., Fischl, A. S., and Carman, G. M. (1998) J. Biol. Chem. 273, 3278–3284; Toke, D. A., Bennett, W. L., Oshiro, J., Wu, W.-I., Voelker, D. R., and Carman, G. M. (1998) J. Biol. Chem. 273, 14331–14338), the disruption of DPP1 and LPP1 produced profound losses of Mg2+-independent PA phosphatase activity. The coincident attenuation of hydrolytic activity against diacylglycerol pyroPhosphate prompted an examination of the effects of these disruptions on hydrolysis of Isoprenoid pyroPhosphates. Disruption of either LPP1 or DPP1 caused respective decreases of about 25 and 75% in Mg2+-independent hydrolysis of several Isoprenoid Phosphates by particulate fractions isolated from these cells. The particulate and cytosolic fractions from the double disruption (lpp1Δ dpp1Δ) showed essentially complete loss of Mg2+-independent hydrolytic activity toward dolichyl Phosphate (dolichyl-P), dolichyl pyroPhosphate (dolichyl-P-P), farnesyl pyroPhosphate (farnesyl-P-P), and geranylgeranyl pyroPhosphate (geranylgeranyl-P-P). However, a modest Mg2+-stimulated activity toward PA and dolichyl-P was retained in cytosol fromlpp1Δ dpp1Δ cells. The action of Dpp1p on isoprenyl pyroPhosphates was confirmed by characterization of the hydrolysis of geranylgeranyl-P-P by the purified protein. These results indicate that LPP1 and DPP1 account for most of the hydrolytic activities toward dolichyl-P-P, dolichyl-P, farnesyl-P-P, and geranylgeranyl-P-P but also suggest that yeast contain other enzymes capable of dephosphorylating these essential Isoprenoid intermediates.
