The Experts below are selected from a list of 243 Experts worldwide ranked by ideXlab platform
Nicola S. Carter - One of the best experts on this subject based on the ideXlab platform.
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Purine and pyrimidine metabolism in Leishmania.
Advances in Experimental Medicine and Biology, 2020Co-Authors: Nicola S. Carter, Phillip A Yates, Cassandra S. Arendt, Jan M. Boitz, Buddy UllmanAbstract:Purines and pyrimidines are indispensable to all life, performing many vital functions for cells: ATP serves as the universal currency of cellular energy, cAMP and cGMP are key second messenger molecules, Purine and pyrimidine nucleotides are precursors for activated forms of both carbohydrates and lipids, nucleotide derivatives of vitamins are essential cofactors in metabolic processes, and nucleoside triphosphates are the immediate precursors for DNA and RNA synthesis. Unlike their mammalian and insect hosts, Leishmania lack the metabolic machinery to make Purine nudeotides de novo and must rely on their host for preformed Purines. The obligatory nature of Purine salvage offers, therefore, a plethora of potential targets for drug targeting, and the pathway has consequently been the focus of considerable scientific investigation. In contrast, Leishmania are prototrophic for pyrimidines and also express a small complement of pyrimidine salvage enzymes. Because the pyrimidine nucleotide biosynthetic pathways of Leishmania and humans are similar, pyrimidine metabolism in Leishmania has generally been considered less amenable to therapeutic manipulation than the Purine salvage pathway. However, evidence garnered from a variety of parasitic protozoa suggests that the selective inhibition of pyrimidine biosynthetic enzymes offers a rational therapeutic paradigm. In this chapter, we present an overview of the Purine and pyrimidine pathways in Leishmania, make comparisons to the equivalent pathways in their mammalian host, and explore how these pathways might be amenable to selective therapeutic targeting.
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a role for adenine nucleotides in the sensing mechanism to Purine starvation in leishmania donovani
Molecular Microbiology, 2016Co-Authors: Jessica L Martin, Phillip A Yates, Buddy Ullman, Jan M. Boitz, Dennis R Koop, Audrey L Fulwiler, Maria B Cassera, Nicola S. CarterAbstract:Purine salvage by Leishmania is an obligatory nutritional process that impacts both cell viability and growth. Previously, we have demonstrated that the removal of Purines in culture provokes significant metabolic changes that enable Leishmania to survive prolonged periods of Purine starvation. In order to understand how Leishmania sense and respond to changes in their Purine environment, we have exploited several Purine pathway mutants, some in which adenine and guanine nucleotide metabolism is uncoupled. While wild type parasites grow in any one of a variety of naturally occurring Purines, the proliferation of these Purine pathway mutants requires specific types or combinations of exogenous Purines. By culturing Purine pathway mutants in high levels of extracellular Purines that are either permissive or non-permissive for growth and monitoring for previously defined markers of the adaptive response to Purine starvation, we determined that adaptation arises from a surveillance of intracellular Purine nucleotide pools rather than from a direct sensing of the extracellular Purine content of the environment. Specifically, our data suggest that perturbation of intracellular adenine-containing nucleotide pools provides a crucial signal for inducing the metabolic changes necessary for the long-term survival of Leishmania in a Purine-scarce environment.
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a role for adenine nucleotides in the sensing mechanism to Purine starvation in leishmania donovani
Molecular Microbiology, 2016Co-Authors: Jessica L Martin, Phillip A Yates, Buddy Ullman, Jan M. Boitz, Dennis R Koop, Audrey L Fulwiler, Maria B Cassera, Nicola S. CarterAbstract:Summary Purine salvage by Leishmania is an obligatory nutritional process that impacts both cell viability and growth. Previously, we have demonstrated that the removal of Purines in culture provokes significant metabolic changes that enable Leishmania to survive prolonged periods of Purine starvation. In order to understand how Leishmania sense and respond to changes in their Purine environment, we have exploited several Purine pathway mutants, some in which adenine and guanine nucleotide metabolism is uncoupled. While wild type parasites grow in any one of a variety of naturally occurring Purines, the proliferation of these Purine pathway mutants requires specific types or combinations of exogenous Purines. By culturing Purine pathway mutants in high levels of extracellular Purines that are either permissive or non-permissive for growth and monitoring for previously defined markers of the adaptive response to Purine starvation, we determined that adaptation arises from a surveillance of intracellular Purine nucleotide pools rather than from a direct sensing of the extracellular Purine content of the environment. Specifically, our data suggest that perturbation of intracellular adenine-containing nucleotide pools provides a crucial signal for inducing the metabolic changes necessary for the long-term survival of Leishmania in a Purine-scarce environment. This article is protected by copyright. All rights reserved.
Buddy Ullman - One of the best experts on this subject based on the ideXlab platform.
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Purine and pyrimidine metabolism in Leishmania.
Advances in Experimental Medicine and Biology, 2020Co-Authors: Nicola S. Carter, Phillip A Yates, Cassandra S. Arendt, Jan M. Boitz, Buddy UllmanAbstract:Purines and pyrimidines are indispensable to all life, performing many vital functions for cells: ATP serves as the universal currency of cellular energy, cAMP and cGMP are key second messenger molecules, Purine and pyrimidine nucleotides are precursors for activated forms of both carbohydrates and lipids, nucleotide derivatives of vitamins are essential cofactors in metabolic processes, and nucleoside triphosphates are the immediate precursors for DNA and RNA synthesis. Unlike their mammalian and insect hosts, Leishmania lack the metabolic machinery to make Purine nudeotides de novo and must rely on their host for preformed Purines. The obligatory nature of Purine salvage offers, therefore, a plethora of potential targets for drug targeting, and the pathway has consequently been the focus of considerable scientific investigation. In contrast, Leishmania are prototrophic for pyrimidines and also express a small complement of pyrimidine salvage enzymes. Because the pyrimidine nucleotide biosynthetic pathways of Leishmania and humans are similar, pyrimidine metabolism in Leishmania has generally been considered less amenable to therapeutic manipulation than the Purine salvage pathway. However, evidence garnered from a variety of parasitic protozoa suggests that the selective inhibition of pyrimidine biosynthetic enzymes offers a rational therapeutic paradigm. In this chapter, we present an overview of the Purine and pyrimidine pathways in Leishmania, make comparisons to the equivalent pathways in their mammalian host, and explore how these pathways might be amenable to selective therapeutic targeting.
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a role for adenine nucleotides in the sensing mechanism to Purine starvation in leishmania donovani
Molecular Microbiology, 2016Co-Authors: Jessica L Martin, Phillip A Yates, Buddy Ullman, Jan M. Boitz, Dennis R Koop, Audrey L Fulwiler, Maria B Cassera, Nicola S. CarterAbstract:Purine salvage by Leishmania is an obligatory nutritional process that impacts both cell viability and growth. Previously, we have demonstrated that the removal of Purines in culture provokes significant metabolic changes that enable Leishmania to survive prolonged periods of Purine starvation. In order to understand how Leishmania sense and respond to changes in their Purine environment, we have exploited several Purine pathway mutants, some in which adenine and guanine nucleotide metabolism is uncoupled. While wild type parasites grow in any one of a variety of naturally occurring Purines, the proliferation of these Purine pathway mutants requires specific types or combinations of exogenous Purines. By culturing Purine pathway mutants in high levels of extracellular Purines that are either permissive or non-permissive for growth and monitoring for previously defined markers of the adaptive response to Purine starvation, we determined that adaptation arises from a surveillance of intracellular Purine nucleotide pools rather than from a direct sensing of the extracellular Purine content of the environment. Specifically, our data suggest that perturbation of intracellular adenine-containing nucleotide pools provides a crucial signal for inducing the metabolic changes necessary for the long-term survival of Leishmania in a Purine-scarce environment.
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a role for adenine nucleotides in the sensing mechanism to Purine starvation in leishmania donovani
Molecular Microbiology, 2016Co-Authors: Jessica L Martin, Phillip A Yates, Buddy Ullman, Jan M. Boitz, Dennis R Koop, Audrey L Fulwiler, Maria B Cassera, Nicola S. CarterAbstract:Summary Purine salvage by Leishmania is an obligatory nutritional process that impacts both cell viability and growth. Previously, we have demonstrated that the removal of Purines in culture provokes significant metabolic changes that enable Leishmania to survive prolonged periods of Purine starvation. In order to understand how Leishmania sense and respond to changes in their Purine environment, we have exploited several Purine pathway mutants, some in which adenine and guanine nucleotide metabolism is uncoupled. While wild type parasites grow in any one of a variety of naturally occurring Purines, the proliferation of these Purine pathway mutants requires specific types or combinations of exogenous Purines. By culturing Purine pathway mutants in high levels of extracellular Purines that are either permissive or non-permissive for growth and monitoring for previously defined markers of the adaptive response to Purine starvation, we determined that adaptation arises from a surveillance of intracellular Purine nucleotide pools rather than from a direct sensing of the extracellular Purine content of the environment. Specifically, our data suggest that perturbation of intracellular adenine-containing nucleotide pools provides a crucial signal for inducing the metabolic changes necessary for the long-term survival of Leishmania in a Purine-scarce environment. This article is protected by copyright. All rights reserved.
Jan M. Boitz - One of the best experts on this subject based on the ideXlab platform.
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Purine and pyrimidine metabolism in Leishmania.
Advances in Experimental Medicine and Biology, 2020Co-Authors: Nicola S. Carter, Phillip A Yates, Cassandra S. Arendt, Jan M. Boitz, Buddy UllmanAbstract:Purines and pyrimidines are indispensable to all life, performing many vital functions for cells: ATP serves as the universal currency of cellular energy, cAMP and cGMP are key second messenger molecules, Purine and pyrimidine nucleotides are precursors for activated forms of both carbohydrates and lipids, nucleotide derivatives of vitamins are essential cofactors in metabolic processes, and nucleoside triphosphates are the immediate precursors for DNA and RNA synthesis. Unlike their mammalian and insect hosts, Leishmania lack the metabolic machinery to make Purine nudeotides de novo and must rely on their host for preformed Purines. The obligatory nature of Purine salvage offers, therefore, a plethora of potential targets for drug targeting, and the pathway has consequently been the focus of considerable scientific investigation. In contrast, Leishmania are prototrophic for pyrimidines and also express a small complement of pyrimidine salvage enzymes. Because the pyrimidine nucleotide biosynthetic pathways of Leishmania and humans are similar, pyrimidine metabolism in Leishmania has generally been considered less amenable to therapeutic manipulation than the Purine salvage pathway. However, evidence garnered from a variety of parasitic protozoa suggests that the selective inhibition of pyrimidine biosynthetic enzymes offers a rational therapeutic paradigm. In this chapter, we present an overview of the Purine and pyrimidine pathways in Leishmania, make comparisons to the equivalent pathways in their mammalian host, and explore how these pathways might be amenable to selective therapeutic targeting.
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a role for adenine nucleotides in the sensing mechanism to Purine starvation in leishmania donovani
Molecular Microbiology, 2016Co-Authors: Jessica L Martin, Phillip A Yates, Buddy Ullman, Jan M. Boitz, Dennis R Koop, Audrey L Fulwiler, Maria B Cassera, Nicola S. CarterAbstract:Purine salvage by Leishmania is an obligatory nutritional process that impacts both cell viability and growth. Previously, we have demonstrated that the removal of Purines in culture provokes significant metabolic changes that enable Leishmania to survive prolonged periods of Purine starvation. In order to understand how Leishmania sense and respond to changes in their Purine environment, we have exploited several Purine pathway mutants, some in which adenine and guanine nucleotide metabolism is uncoupled. While wild type parasites grow in any one of a variety of naturally occurring Purines, the proliferation of these Purine pathway mutants requires specific types or combinations of exogenous Purines. By culturing Purine pathway mutants in high levels of extracellular Purines that are either permissive or non-permissive for growth and monitoring for previously defined markers of the adaptive response to Purine starvation, we determined that adaptation arises from a surveillance of intracellular Purine nucleotide pools rather than from a direct sensing of the extracellular Purine content of the environment. Specifically, our data suggest that perturbation of intracellular adenine-containing nucleotide pools provides a crucial signal for inducing the metabolic changes necessary for the long-term survival of Leishmania in a Purine-scarce environment.
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a role for adenine nucleotides in the sensing mechanism to Purine starvation in leishmania donovani
Molecular Microbiology, 2016Co-Authors: Jessica L Martin, Phillip A Yates, Buddy Ullman, Jan M. Boitz, Dennis R Koop, Audrey L Fulwiler, Maria B Cassera, Nicola S. CarterAbstract:Summary Purine salvage by Leishmania is an obligatory nutritional process that impacts both cell viability and growth. Previously, we have demonstrated that the removal of Purines in culture provokes significant metabolic changes that enable Leishmania to survive prolonged periods of Purine starvation. In order to understand how Leishmania sense and respond to changes in their Purine environment, we have exploited several Purine pathway mutants, some in which adenine and guanine nucleotide metabolism is uncoupled. While wild type parasites grow in any one of a variety of naturally occurring Purines, the proliferation of these Purine pathway mutants requires specific types or combinations of exogenous Purines. By culturing Purine pathway mutants in high levels of extracellular Purines that are either permissive or non-permissive for growth and monitoring for previously defined markers of the adaptive response to Purine starvation, we determined that adaptation arises from a surveillance of intracellular Purine nucleotide pools rather than from a direct sensing of the extracellular Purine content of the environment. Specifically, our data suggest that perturbation of intracellular adenine-containing nucleotide pools provides a crucial signal for inducing the metabolic changes necessary for the long-term survival of Leishmania in a Purine-scarce environment. This article is protected by copyright. All rights reserved.
Phillip A Yates - One of the best experts on this subject based on the ideXlab platform.
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Purine and pyrimidine metabolism in Leishmania.
Advances in Experimental Medicine and Biology, 2020Co-Authors: Nicola S. Carter, Phillip A Yates, Cassandra S. Arendt, Jan M. Boitz, Buddy UllmanAbstract:Purines and pyrimidines are indispensable to all life, performing many vital functions for cells: ATP serves as the universal currency of cellular energy, cAMP and cGMP are key second messenger molecules, Purine and pyrimidine nucleotides are precursors for activated forms of both carbohydrates and lipids, nucleotide derivatives of vitamins are essential cofactors in metabolic processes, and nucleoside triphosphates are the immediate precursors for DNA and RNA synthesis. Unlike their mammalian and insect hosts, Leishmania lack the metabolic machinery to make Purine nudeotides de novo and must rely on their host for preformed Purines. The obligatory nature of Purine salvage offers, therefore, a plethora of potential targets for drug targeting, and the pathway has consequently been the focus of considerable scientific investigation. In contrast, Leishmania are prototrophic for pyrimidines and also express a small complement of pyrimidine salvage enzymes. Because the pyrimidine nucleotide biosynthetic pathways of Leishmania and humans are similar, pyrimidine metabolism in Leishmania has generally been considered less amenable to therapeutic manipulation than the Purine salvage pathway. However, evidence garnered from a variety of parasitic protozoa suggests that the selective inhibition of pyrimidine biosynthetic enzymes offers a rational therapeutic paradigm. In this chapter, we present an overview of the Purine and pyrimidine pathways in Leishmania, make comparisons to the equivalent pathways in their mammalian host, and explore how these pathways might be amenable to selective therapeutic targeting.
-
a role for adenine nucleotides in the sensing mechanism to Purine starvation in leishmania donovani
Molecular Microbiology, 2016Co-Authors: Jessica L Martin, Phillip A Yates, Buddy Ullman, Jan M. Boitz, Dennis R Koop, Audrey L Fulwiler, Maria B Cassera, Nicola S. CarterAbstract:Purine salvage by Leishmania is an obligatory nutritional process that impacts both cell viability and growth. Previously, we have demonstrated that the removal of Purines in culture provokes significant metabolic changes that enable Leishmania to survive prolonged periods of Purine starvation. In order to understand how Leishmania sense and respond to changes in their Purine environment, we have exploited several Purine pathway mutants, some in which adenine and guanine nucleotide metabolism is uncoupled. While wild type parasites grow in any one of a variety of naturally occurring Purines, the proliferation of these Purine pathway mutants requires specific types or combinations of exogenous Purines. By culturing Purine pathway mutants in high levels of extracellular Purines that are either permissive or non-permissive for growth and monitoring for previously defined markers of the adaptive response to Purine starvation, we determined that adaptation arises from a surveillance of intracellular Purine nucleotide pools rather than from a direct sensing of the extracellular Purine content of the environment. Specifically, our data suggest that perturbation of intracellular adenine-containing nucleotide pools provides a crucial signal for inducing the metabolic changes necessary for the long-term survival of Leishmania in a Purine-scarce environment.
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a role for adenine nucleotides in the sensing mechanism to Purine starvation in leishmania donovani
Molecular Microbiology, 2016Co-Authors: Jessica L Martin, Phillip A Yates, Buddy Ullman, Jan M. Boitz, Dennis R Koop, Audrey L Fulwiler, Maria B Cassera, Nicola S. CarterAbstract:Summary Purine salvage by Leishmania is an obligatory nutritional process that impacts both cell viability and growth. Previously, we have demonstrated that the removal of Purines in culture provokes significant metabolic changes that enable Leishmania to survive prolonged periods of Purine starvation. In order to understand how Leishmania sense and respond to changes in their Purine environment, we have exploited several Purine pathway mutants, some in which adenine and guanine nucleotide metabolism is uncoupled. While wild type parasites grow in any one of a variety of naturally occurring Purines, the proliferation of these Purine pathway mutants requires specific types or combinations of exogenous Purines. By culturing Purine pathway mutants in high levels of extracellular Purines that are either permissive or non-permissive for growth and monitoring for previously defined markers of the adaptive response to Purine starvation, we determined that adaptation arises from a surveillance of intracellular Purine nucleotide pools rather than from a direct sensing of the extracellular Purine content of the environment. Specifically, our data suggest that perturbation of intracellular adenine-containing nucleotide pools provides a crucial signal for inducing the metabolic changes necessary for the long-term survival of Leishmania in a Purine-scarce environment. This article is protected by copyright. All rights reserved.
Jessica L Martin - One of the best experts on this subject based on the ideXlab platform.
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a role for adenine nucleotides in the sensing mechanism to Purine starvation in leishmania donovani
Molecular Microbiology, 2016Co-Authors: Jessica L Martin, Phillip A Yates, Buddy Ullman, Jan M. Boitz, Dennis R Koop, Audrey L Fulwiler, Maria B Cassera, Nicola S. CarterAbstract:Purine salvage by Leishmania is an obligatory nutritional process that impacts both cell viability and growth. Previously, we have demonstrated that the removal of Purines in culture provokes significant metabolic changes that enable Leishmania to survive prolonged periods of Purine starvation. In order to understand how Leishmania sense and respond to changes in their Purine environment, we have exploited several Purine pathway mutants, some in which adenine and guanine nucleotide metabolism is uncoupled. While wild type parasites grow in any one of a variety of naturally occurring Purines, the proliferation of these Purine pathway mutants requires specific types or combinations of exogenous Purines. By culturing Purine pathway mutants in high levels of extracellular Purines that are either permissive or non-permissive for growth and monitoring for previously defined markers of the adaptive response to Purine starvation, we determined that adaptation arises from a surveillance of intracellular Purine nucleotide pools rather than from a direct sensing of the extracellular Purine content of the environment. Specifically, our data suggest that perturbation of intracellular adenine-containing nucleotide pools provides a crucial signal for inducing the metabolic changes necessary for the long-term survival of Leishmania in a Purine-scarce environment.
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a role for adenine nucleotides in the sensing mechanism to Purine starvation in leishmania donovani
Molecular Microbiology, 2016Co-Authors: Jessica L Martin, Phillip A Yates, Buddy Ullman, Jan M. Boitz, Dennis R Koop, Audrey L Fulwiler, Maria B Cassera, Nicola S. CarterAbstract:Summary Purine salvage by Leishmania is an obligatory nutritional process that impacts both cell viability and growth. Previously, we have demonstrated that the removal of Purines in culture provokes significant metabolic changes that enable Leishmania to survive prolonged periods of Purine starvation. In order to understand how Leishmania sense and respond to changes in their Purine environment, we have exploited several Purine pathway mutants, some in which adenine and guanine nucleotide metabolism is uncoupled. While wild type parasites grow in any one of a variety of naturally occurring Purines, the proliferation of these Purine pathway mutants requires specific types or combinations of exogenous Purines. By culturing Purine pathway mutants in high levels of extracellular Purines that are either permissive or non-permissive for growth and monitoring for previously defined markers of the adaptive response to Purine starvation, we determined that adaptation arises from a surveillance of intracellular Purine nucleotide pools rather than from a direct sensing of the extracellular Purine content of the environment. Specifically, our data suggest that perturbation of intracellular adenine-containing nucleotide pools provides a crucial signal for inducing the metabolic changes necessary for the long-term survival of Leishmania in a Purine-scarce environment. This article is protected by copyright. All rights reserved.
