The Experts below are selected from a list of 9 Experts worldwide ranked by ideXlab platform

Socrates E. Papapoulos - One of the best experts on this subject based on the ideXlab platform.

  • farnesyl pyrophosphate synthase is the molecular target of nitrogen containing bisphosphonates
    Biochemical and Biophysical Research Communications, 1999
    Co-Authors: E Van Beek, Louis H Cohen, Elsbet J Pieterman, Clemens W.g.m. Löwik, Socrates E. Papapoulos
    Abstract:

    Bisphosphonates (Bps), inhibitors of osteoclastic bone resorption, are used in the treatment of skeletal disorders. Recent evidence indicated that farnesyl pyrophosphate (FPP) synthase and/or isopentenyl pyrophosphate (IPP) isomerase is the intracellular target(s) of bisphosphonate action. To examine which enzyme is specifically affected, we determined the effect of different Bps on incorporation of [14C]mevalonate (MVA), [14C]IPP, and [14C]dimethylallyl pyrophosphate (DMAPP) into polyisoprenyl pyrophosphates in a homogenate of bovine brain. HPLC analysis revealed that the three intermediates were incorporated into FPP and geranylgeranyl pyrophosphate (GGPP). In contrast to clodronate, the nitrogen-containing Bps (NBps), alendronate, risedronate, olpadronate, and ibandronate, completely blocked FPP and GGPP formation and induced in incubations with [14C]MVA a 3- to 5-fold increase in incorporation of label into IPP and/or DMAPP. Using a method that could distinguish DMAPP from IPP on basis of their difference in stability in acid, we found that none of the NBps affected the conversion of [14C]IPP into DMAPP, catalyzed by IPP isomerase, excluding this enzyme as target of NBp action. On the basis of these and our previous findings, we conclude that none of the enzymes up- or downstream of FPP synthase are affected by NBps, and FPP synthase is, therefore, the exclusive molecular target of NBp action. Chemicals/CAS: Carbon Radioisotopes; Carbon-Carbon Double Bond Isomerases, EC 5.3.3.-; Dimethylallyltranstransferase, EC 2.5.1.1; Diphosphonates; Enzyme Inhibitors; indolepropanol phosphate, 40716-80-1; Indoles; isopentenyldiphosphate delta-isomerase, EC 5.3.3.2; Mevalonic Acid, 150-97-0

Zhezhi Wang - One of the best experts on this subject based on the ideXlab platform.

  • Putative unigenes related to the biosynthesis of hyperforin, hypericin, and melatonin.
    2012
    Co-Authors: Ying Wang, Wenping Hua, Yuan Zhang, Zhezhi Wang
    Abstract:

    NU, number of unigenes; MNCG, maximum number of coding genes. MAT, Dimethylallyltranstransferase; Hyp-1, Hypericum perforatum phenolic oxidative coupling protein; MAT, Dimethylallyltranstransferase; DXS, 1-D-deoxyxylulose 5-phosphate synthase; DXR, 1-deoxy-D-xylulose 5-phosphate reductoisomerase; CMS, 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase; CMK, 4-(cytidine 5′-diphospho)-2-C-methyl-D- erythritol kinase; MCS, 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase; HDS, (E)-4-hydroxy-3- methylbut-2-enyl-diphosphate synthase; IDS, isopentenyl-diphosphate:NAD(P)+ oxidoreductase; IPI, isopentenylpyrophosphate isomerase; GPPS, geranylgeranyl pyrophosphate synthase; AS, anthranilate synthase; PAT, phosphoribosylanthranilate transferase; PAI, phosphoribosylanthranilate isomerase; IGPS, indole-3-glycerol phosphate synthase; TSA, Tryptophan synthase alpha chain; TSB, Tryptophan synthase beta chain; TDC, tryptophan decarboxylase; TPH, tryptophan hydroxylase.

  • Putative biosynthesis pathways for hypericin (A), hyperforin (B), and melatonin (C) in Hypericum perforatum.
    2012
    Co-Authors: Ying Wang, Wenping Hua, Yuan Zhang, Zhezhi Wang
    Abstract:

    Dashed box within (B) occurs in animals. Hyp-1, Hypericum perforatum phenolic oxidative coupling protein; MEP pathway, non-mevalonate pathway; MAT, Dimethylallyltranstransferase; AS I, anthranilate synthase I; AS II, anthranilate synthase II; PAT, phosphoribosylanthranilate transferase; PAI, phosphoribosylanthranilate isomerase; IGPS, indole-3-glycerol phosphate synthase; TSA, Tryptophan synthase alpha chain; TSB, Tryptophan synthase beta chain; TDC, tryptophan decarboxylase; TPH, tryptophan hydroxylase; ORCA3, octadecanoid-derivative responsive Catharanthus AP2-domain protein 3; DXS, 1-D-deoxyxylulose 5-phosphate synthase; DXR, 1-deoxy-D-xylulose 5-phosphate reductoisomerase; CMS, 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase; CMK, 4-(cytidine 5′-diphospho)-2-C-methyl-D-erythritol kinase; MCS, 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase; HDS, (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase; IDS, isopentenyl-diphosphate:NAD(P)+ oxidoreductase; IPI, isopentenylpyrophosphate isomerase; GPPS, geranylgeranyl pyrophosphate synthase; DMAPP, dimethylallyl diphosphate; IPP, isopentenyl diphosphate; GPP, geranyl diphosphate; MEP, 2-C-methyl-Derythritol-4-phosphate; CDP-ME, 4-(cytidine-5′-diphospho)-2-C-methyl-Derythritol; CDP-MEP, 2-phospho-4-(cytidine-5′-diphospho)-2-C- methyl-Derythritol; Me-cPP, 2-C-methyl-D-erythritol-2,4, cyclodiphosphate; HMBPP, 1-hydroxy-2-methyl- 2-(E)-butenyl 4-diphosphate.

E Van Beek - One of the best experts on this subject based on the ideXlab platform.

  • farnesyl pyrophosphate synthase is the molecular target of nitrogen containing bisphosphonates
    Biochemical and Biophysical Research Communications, 1999
    Co-Authors: E Van Beek, Louis H Cohen, Elsbet J Pieterman, Clemens W.g.m. Löwik, Socrates E. Papapoulos
    Abstract:

    Bisphosphonates (Bps), inhibitors of osteoclastic bone resorption, are used in the treatment of skeletal disorders. Recent evidence indicated that farnesyl pyrophosphate (FPP) synthase and/or isopentenyl pyrophosphate (IPP) isomerase is the intracellular target(s) of bisphosphonate action. To examine which enzyme is specifically affected, we determined the effect of different Bps on incorporation of [14C]mevalonate (MVA), [14C]IPP, and [14C]dimethylallyl pyrophosphate (DMAPP) into polyisoprenyl pyrophosphates in a homogenate of bovine brain. HPLC analysis revealed that the three intermediates were incorporated into FPP and geranylgeranyl pyrophosphate (GGPP). In contrast to clodronate, the nitrogen-containing Bps (NBps), alendronate, risedronate, olpadronate, and ibandronate, completely blocked FPP and GGPP formation and induced in incubations with [14C]MVA a 3- to 5-fold increase in incorporation of label into IPP and/or DMAPP. Using a method that could distinguish DMAPP from IPP on basis of their difference in stability in acid, we found that none of the NBps affected the conversion of [14C]IPP into DMAPP, catalyzed by IPP isomerase, excluding this enzyme as target of NBp action. On the basis of these and our previous findings, we conclude that none of the enzymes up- or downstream of FPP synthase are affected by NBps, and FPP synthase is, therefore, the exclusive molecular target of NBp action. Chemicals/CAS: Carbon Radioisotopes; Carbon-Carbon Double Bond Isomerases, EC 5.3.3.-; Dimethylallyltranstransferase, EC 2.5.1.1; Diphosphonates; Enzyme Inhibitors; indolepropanol phosphate, 40716-80-1; Indoles; isopentenyldiphosphate delta-isomerase, EC 5.3.3.2; Mevalonic Acid, 150-97-0

Ying Wang - One of the best experts on this subject based on the ideXlab platform.

  • Putative unigenes related to the biosynthesis of hyperforin, hypericin, and melatonin.
    2012
    Co-Authors: Ying Wang, Wenping Hua, Yuan Zhang, Zhezhi Wang
    Abstract:

    NU, number of unigenes; MNCG, maximum number of coding genes. MAT, Dimethylallyltranstransferase; Hyp-1, Hypericum perforatum phenolic oxidative coupling protein; MAT, Dimethylallyltranstransferase; DXS, 1-D-deoxyxylulose 5-phosphate synthase; DXR, 1-deoxy-D-xylulose 5-phosphate reductoisomerase; CMS, 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase; CMK, 4-(cytidine 5′-diphospho)-2-C-methyl-D- erythritol kinase; MCS, 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase; HDS, (E)-4-hydroxy-3- methylbut-2-enyl-diphosphate synthase; IDS, isopentenyl-diphosphate:NAD(P)+ oxidoreductase; IPI, isopentenylpyrophosphate isomerase; GPPS, geranylgeranyl pyrophosphate synthase; AS, anthranilate synthase; PAT, phosphoribosylanthranilate transferase; PAI, phosphoribosylanthranilate isomerase; IGPS, indole-3-glycerol phosphate synthase; TSA, Tryptophan synthase alpha chain; TSB, Tryptophan synthase beta chain; TDC, tryptophan decarboxylase; TPH, tryptophan hydroxylase.

  • Putative biosynthesis pathways for hypericin (A), hyperforin (B), and melatonin (C) in Hypericum perforatum.
    2012
    Co-Authors: Ying Wang, Wenping Hua, Yuan Zhang, Zhezhi Wang
    Abstract:

    Dashed box within (B) occurs in animals. Hyp-1, Hypericum perforatum phenolic oxidative coupling protein; MEP pathway, non-mevalonate pathway; MAT, Dimethylallyltranstransferase; AS I, anthranilate synthase I; AS II, anthranilate synthase II; PAT, phosphoribosylanthranilate transferase; PAI, phosphoribosylanthranilate isomerase; IGPS, indole-3-glycerol phosphate synthase; TSA, Tryptophan synthase alpha chain; TSB, Tryptophan synthase beta chain; TDC, tryptophan decarboxylase; TPH, tryptophan hydroxylase; ORCA3, octadecanoid-derivative responsive Catharanthus AP2-domain protein 3; DXS, 1-D-deoxyxylulose 5-phosphate synthase; DXR, 1-deoxy-D-xylulose 5-phosphate reductoisomerase; CMS, 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase; CMK, 4-(cytidine 5′-diphospho)-2-C-methyl-D-erythritol kinase; MCS, 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase; HDS, (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase; IDS, isopentenyl-diphosphate:NAD(P)+ oxidoreductase; IPI, isopentenylpyrophosphate isomerase; GPPS, geranylgeranyl pyrophosphate synthase; DMAPP, dimethylallyl diphosphate; IPP, isopentenyl diphosphate; GPP, geranyl diphosphate; MEP, 2-C-methyl-Derythritol-4-phosphate; CDP-ME, 4-(cytidine-5′-diphospho)-2-C-methyl-Derythritol; CDP-MEP, 2-phospho-4-(cytidine-5′-diphospho)-2-C- methyl-Derythritol; Me-cPP, 2-C-methyl-D-erythritol-2,4, cyclodiphosphate; HMBPP, 1-hydroxy-2-methyl- 2-(E)-butenyl 4-diphosphate.

Louis H Cohen - One of the best experts on this subject based on the ideXlab platform.

  • farnesyl pyrophosphate synthase is the molecular target of nitrogen containing bisphosphonates
    Biochemical and Biophysical Research Communications, 1999
    Co-Authors: E Van Beek, Louis H Cohen, Elsbet J Pieterman, Clemens W.g.m. Löwik, Socrates E. Papapoulos
    Abstract:

    Bisphosphonates (Bps), inhibitors of osteoclastic bone resorption, are used in the treatment of skeletal disorders. Recent evidence indicated that farnesyl pyrophosphate (FPP) synthase and/or isopentenyl pyrophosphate (IPP) isomerase is the intracellular target(s) of bisphosphonate action. To examine which enzyme is specifically affected, we determined the effect of different Bps on incorporation of [14C]mevalonate (MVA), [14C]IPP, and [14C]dimethylallyl pyrophosphate (DMAPP) into polyisoprenyl pyrophosphates in a homogenate of bovine brain. HPLC analysis revealed that the three intermediates were incorporated into FPP and geranylgeranyl pyrophosphate (GGPP). In contrast to clodronate, the nitrogen-containing Bps (NBps), alendronate, risedronate, olpadronate, and ibandronate, completely blocked FPP and GGPP formation and induced in incubations with [14C]MVA a 3- to 5-fold increase in incorporation of label into IPP and/or DMAPP. Using a method that could distinguish DMAPP from IPP on basis of their difference in stability in acid, we found that none of the NBps affected the conversion of [14C]IPP into DMAPP, catalyzed by IPP isomerase, excluding this enzyme as target of NBp action. On the basis of these and our previous findings, we conclude that none of the enzymes up- or downstream of FPP synthase are affected by NBps, and FPP synthase is, therefore, the exclusive molecular target of NBp action. Chemicals/CAS: Carbon Radioisotopes; Carbon-Carbon Double Bond Isomerases, EC 5.3.3.-; Dimethylallyltranstransferase, EC 2.5.1.1; Diphosphonates; Enzyme Inhibitors; indolepropanol phosphate, 40716-80-1; Indoles; isopentenyldiphosphate delta-isomerase, EC 5.3.3.2; Mevalonic Acid, 150-97-0