The Experts below are selected from a list of 306 Experts worldwide ranked by ideXlab platform
Tomoyoshi Nozaki - One of the best experts on this subject based on the ideXlab platform.
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Current Therapeutics, Their Problems, and Sulfur-Containing-Amino-Acid Metabolism as a Novel Target against Infections by “Amitochondriate” Protozoan Parasites
Clinical microbiology reviews, 2007Co-Authors: Vahab Ali, Tomoyoshi NozakiAbstract:The “amitochondriate” protozoan parasites of humans Entamoeba histolytica, Giardia intestinalis, and Trichomonas vaginalis share many biochemical features, e.g., energy and Amino Acid metabolism, a spectrum of drugs for their treatment, and the occurrence of drug resistance. These parasites possess metabolic pathways that are divergent from those of their mammalian hosts and are often considered to be good targets for drug development. Sulfur-Containing-Amino-Acid metabolism represents one such divergent metabolic pathway, namely, the cysteine biosynthetic pathway and methionine γ-lyase-mediated catabolism of Sulfur-Containing Amino Acids, which are present in T. vaginalis and E. histolytica but absent in G. intestinalis. These pathways are potentially exploitable for development of drugs against amoebiasis and trichomoniasis. For instance, l-trifluoromethionine, which is catalyzed by methionine γ-lyase and produces a toxic product, is effective against T. vaginalis and E. histolytica parasites in vitro and in vivo and may represent a good lead compound. In this review, we summarize the biology of these microaerophilic parasites, their clinical manifestation and epidemiology of disease, chemotherapeutics, the modes of action of representative drugs, and problems related to these drugs, including drug resistance. We further discuss our approach to exploit unique Sulfur-Containing-Amino-Acid metabolism, focusing on development of drugs against E. histolytica.
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current therapeutics their problems and sulfur containing Amino Acid metabolism as a novel target against infections by amitochondriate protozoan parasites
Clinical Microbiology Reviews, 2007Co-Authors: Vahab Ali, Tomoyoshi NozakiAbstract:The “amitochondriate” protozoan parasites of humans Entamoeba histolytica, Giardia intestinalis, and Trichomonas vaginalis share many biochemical features, e.g., energy and Amino Acid metabolism, a spectrum of drugs for their treatment, and the occurrence of drug resistance. These parasites possess metabolic pathways that are divergent from those of their mammalian hosts and are often considered to be good targets for drug development. Sulfur-Containing-Amino-Acid metabolism represents one such divergent metabolic pathway, namely, the cysteine biosynthetic pathway and methionine γ-lyase-mediated catabolism of Sulfur-Containing Amino Acids, which are present in T. vaginalis and E. histolytica but absent in G. intestinalis. These pathways are potentially exploitable for development of drugs against amoebiasis and trichomoniasis. For instance, l-trifluoromethionine, which is catalyzed by methionine γ-lyase and produces a toxic product, is effective against T. vaginalis and E. histolytica parasites in vitro and in vivo and may represent a good lead compound. In this review, we summarize the biology of these microaerophilic parasites, their clinical manifestation and epidemiology of disease, chemotherapeutics, the modes of action of representative drugs, and problems related to these drugs, including drug resistance. We further discuss our approach to exploit unique Sulfur-Containing-Amino-Acid metabolism, focusing on development of drugs against E. histolytica.
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Sulfur-Containing Amino Acid metabolism in parasitic protozoa
Advances in parasitology, 2005Co-Authors: Tomoyoshi Nozaki, Vahab Ali, Masaharu TokoroAbstract:Sulfur-Containing Amino Acids play indispensable roles in a wide variety of biological activities including protein synthesis, methylation, and biosynthesis of polyamines and glutathione. Biosynthesis and catabolism of these Amino Acids need to be carefully regulated to achieve the requirement of the above-mentioned activities and also to eliminate toxicity attributable to the Amino Acids. Genome-wide analyses of enzymes involved in the metabolic pathways of Sulfur-Containing Amino Acids, including transsulfuration, sulfur assimilatory de novo cysteine biosynthesis, methionine cycle, and degradation, using genome databases available from a variety of parasitic protozoa, reveal remarkable diversity between protozoan parasites and their mammalian hosts. Thus, the Sulfur-Containing Amino Acid metabolic pathways are a rational target for the development of novel chemotherapeutic and prophylactic agents against diseases caused by protozoan parasites. These pathways also demonstrate notable heterogeneity among parasites, suggesting that the metabolism of Sulfur-Containing Amino Acids reflects the diversity of parasitism among parasite species, and probably influences their biology and pathophysiology such as virulence competence and stress defense.
A. Fiala-médioni - One of the best experts on this subject based on the ideXlab platform.
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Carrier of reduced sulfur is a possible role for thiotaurine in symbiotic species from hydrothermal vents with thiotrophic symbionts
Hydrobiologia, 2001Co-Authors: A. M. Pruski, R. De Wit, A. Fiala-médioniAbstract:Experiments supporting the possible role of the free Sulfur-Containing Amino Acid thiotaurine, as a transport and storage compound for sulfide in invertebrates with thiotrophic symbionts are described. The free-living chemotrophic sulfur-oxidising bacterium, Thiobacillus hydrothermalis (strain DSMZ 7121), was used as a model for the symbionts as the actual symbionts have not been obtained in culture. Thiotaurine contains two sulfur atoms, namely the inner sulfone and the outer sulfane sulfur; the latter presents a potential source of reducing equivalents for the symbiont. Nevertheless, we observed no oxidation of thiotaurine when this compound was added to a culture of T. hydrothermalis pre-grown on sulfide. In contrast, when thiotaurine was added to the culture together with an extract of the trophosome of a vestimentiferan tubeworm from the Manus basin, we observed that thiotaurine was oxidised to hypotaurine with concomitant Acidification and formation of bacterial biomass. Thus, the trophosome contains an unknown catalytic factor. We suggest that thiotaurine requires reduction prior to oxidation by T. hydrothermalis and that the host may catalyse the conversion of thiotaurine through the glutathione redox couple. This way, the host can accurately control energy delivery (as reduced sulfur) to the symbionts and can therefore control their symbiont biomass.
Rachel Amir - One of the best experts on this subject based on the ideXlab platform.
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Revisiting the attempts to fortify methionine content in plant seeds
Journal of experimental botany, 2019Co-Authors: Rachel Amir, Hagai Cohen, Yael HachamAbstract:The Sulfur-Containing Amino Acid methionine belongs to the group of essential Amino Acids, meaning that humans and animals must consume it in their diets. However, plant seeds have low levels of methionine, limiting their nutritional potential. For this reason, efforts have been made over the years to increase methionine levels in seeds. Here, we summarize these efforts and focus particularly on those utilizing diverse genetic and molecular tools. Four main approaches are described: (i) expression of methionine-rich storage proteins in a seed-specific manner to incorporate more soluble methionine into the protein fraction; (ii) reduction of methionine-poor storage proteins inside the seeds to reinforce the accumulation of methionine-rich proteins; (iii) silencing methionine catabolic enzymes; and (iv) up-regulation of key biosynthetic enzymes participating in methionine synthesis. We focus on the biosynthetic genes that operate de novo in seeds and that belong to the sulfur assimilation and aspartate family pathways, as well as genes from the methionine-specific pathway. We also include those enzymes that operate in non-seed tissues that contribute to the accumulation of methionine in seeds, such as S-methylmethionine enzymes. Finally, we discuss the biotechnological potential of these manipulations to increase methionine content in plant seeds and their effect on seed germination.
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Higher endogenous methionine in transgenic Arabidopsis seeds affects the composition of storage proteins and lipids
Amino Acids, 2016Co-Authors: Hagai Cohen, Rachel Amir, Agnieszka Pajak, Sudhakar Pandurangan, Frédéric MarsolaisAbstract:Previous in vitro studies demonstrate that exogenous application of the Sulfur-Containing Amino Acid methionine into cultured soybean cotyledons and seedlings reduces the level of methionine-poor storage proteins and elevates those that are methionine-rich. However, the effect of higher endogenous methionine in seeds on the composition of storage products in vivo is not studied yet. We have recently produced transgenic Arabidopsis seeds having significantly higher levels of methionine. In the present work we used these seeds as a model system and profiled them for changes in the abundances of 12S-globulins and 2S-albumins, the two major groups of storage proteins, using 2D-gels and MALDI-MS detection. The findings suggest that higher methionine affects from a certain threshold the accumulation of several subunits of 12S-globulins and 2S-albumins, regardless of their methionine contents, resulting in higher total protein contents. The mRNA abundances of most of the genes encoding these proteins were either correlated or not correlated with the abundances of these proteins, implying that methionine may regulate storage proteins at both transcriptional and post-transcriptional levels. The elevations in total protein contents resulted in reduction of total lipids and altered the fatty Acid composition. Altogether, the data provide new insights into the regulatory roles of elevated methionine levels on seed composition.
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Current understanding of the factors regulating methionine content in vegetative tissues of higher plants
Amino Acids, 2010Co-Authors: Rachel AmirAbstract:Methionine is a nutritionally essential, Sulfur-Containing Amino Acid found in low levels in plants, which often limits its value as a source of dietary protein to humans and animals. Methionine is also a fundamental metabolite in plant cells since, through its first metabolite, S-adenosylmethionine (SAM), it controls the level of several key metabolites, such as ethylene, polyamines and biotin. SAM is also the primary methyl group donor that regulates different processes in plants. Despite its nutritional and regulatory significance, the factors regulating methionine content in plants are not fully known. In this review, we summarize the current knowledge and recent progress made in our understanding of the methionine metabolism. The enzymes and substrates that regulate methionine synthesis were described, as well as the influences of the catabolic pathways of methionine on its content. The current effort to tailor an improvement of methionine content in vegetative tissues with minimal interference in plant growth and productivity is described as well. The accumulated knowledge has provided new insights into the control of methionine level in plants and, in some cases, has resulted in significant improvements in the nutritional value of plants.
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cystathionine γ synthase and threonine synthase operate in concert to regulate carbon flow towards methionine in plants
Trends in Plant Science, 2002Co-Authors: Rachel Amir, Yael Hacham, Gad GaliliAbstract:The Sulfur-Containing Amino Acid methionine is a nutritionally important essential Amino Acid and is the precursor of several metabolites that regulate plant growth and responses to the environment. Methionine production is largely regulated by cystathionine γ-synthase, the first specific enzyme for its synthesis. This enzyme competes in a complex manner with threonine synthase, the last enzyme in threonine biosynthesis, for their common substrate O-phosphohomoserine. New genetic and molecular data suggest that methionine synthesis and catabolism are coordinately regulated by novel post-transcriptional and post-translational mechanisms that are associated with a regulatory part within the N-terminal part of cystathionine γ-synthase.
Vahab Ali - One of the best experts on this subject based on the ideXlab platform.
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Current Therapeutics, Their Problems, and Sulfur-Containing-Amino-Acid Metabolism as a Novel Target against Infections by “Amitochondriate” Protozoan Parasites
Clinical microbiology reviews, 2007Co-Authors: Vahab Ali, Tomoyoshi NozakiAbstract:The “amitochondriate” protozoan parasites of humans Entamoeba histolytica, Giardia intestinalis, and Trichomonas vaginalis share many biochemical features, e.g., energy and Amino Acid metabolism, a spectrum of drugs for their treatment, and the occurrence of drug resistance. These parasites possess metabolic pathways that are divergent from those of their mammalian hosts and are often considered to be good targets for drug development. Sulfur-Containing-Amino-Acid metabolism represents one such divergent metabolic pathway, namely, the cysteine biosynthetic pathway and methionine γ-lyase-mediated catabolism of Sulfur-Containing Amino Acids, which are present in T. vaginalis and E. histolytica but absent in G. intestinalis. These pathways are potentially exploitable for development of drugs against amoebiasis and trichomoniasis. For instance, l-trifluoromethionine, which is catalyzed by methionine γ-lyase and produces a toxic product, is effective against T. vaginalis and E. histolytica parasites in vitro and in vivo and may represent a good lead compound. In this review, we summarize the biology of these microaerophilic parasites, their clinical manifestation and epidemiology of disease, chemotherapeutics, the modes of action of representative drugs, and problems related to these drugs, including drug resistance. We further discuss our approach to exploit unique Sulfur-Containing-Amino-Acid metabolism, focusing on development of drugs against E. histolytica.
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current therapeutics their problems and sulfur containing Amino Acid metabolism as a novel target against infections by amitochondriate protozoan parasites
Clinical Microbiology Reviews, 2007Co-Authors: Vahab Ali, Tomoyoshi NozakiAbstract:The “amitochondriate” protozoan parasites of humans Entamoeba histolytica, Giardia intestinalis, and Trichomonas vaginalis share many biochemical features, e.g., energy and Amino Acid metabolism, a spectrum of drugs for their treatment, and the occurrence of drug resistance. These parasites possess metabolic pathways that are divergent from those of their mammalian hosts and are often considered to be good targets for drug development. Sulfur-Containing-Amino-Acid metabolism represents one such divergent metabolic pathway, namely, the cysteine biosynthetic pathway and methionine γ-lyase-mediated catabolism of Sulfur-Containing Amino Acids, which are present in T. vaginalis and E. histolytica but absent in G. intestinalis. These pathways are potentially exploitable for development of drugs against amoebiasis and trichomoniasis. For instance, l-trifluoromethionine, which is catalyzed by methionine γ-lyase and produces a toxic product, is effective against T. vaginalis and E. histolytica parasites in vitro and in vivo and may represent a good lead compound. In this review, we summarize the biology of these microaerophilic parasites, their clinical manifestation and epidemiology of disease, chemotherapeutics, the modes of action of representative drugs, and problems related to these drugs, including drug resistance. We further discuss our approach to exploit unique Sulfur-Containing-Amino-Acid metabolism, focusing on development of drugs against E. histolytica.
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Sulfur-Containing Amino Acid metabolism in parasitic protozoa
Advances in parasitology, 2005Co-Authors: Tomoyoshi Nozaki, Vahab Ali, Masaharu TokoroAbstract:Sulfur-Containing Amino Acids play indispensable roles in a wide variety of biological activities including protein synthesis, methylation, and biosynthesis of polyamines and glutathione. Biosynthesis and catabolism of these Amino Acids need to be carefully regulated to achieve the requirement of the above-mentioned activities and also to eliminate toxicity attributable to the Amino Acids. Genome-wide analyses of enzymes involved in the metabolic pathways of Sulfur-Containing Amino Acids, including transsulfuration, sulfur assimilatory de novo cysteine biosynthesis, methionine cycle, and degradation, using genome databases available from a variety of parasitic protozoa, reveal remarkable diversity between protozoan parasites and their mammalian hosts. Thus, the Sulfur-Containing Amino Acid metabolic pathways are a rational target for the development of novel chemotherapeutic and prophylactic agents against diseases caused by protozoan parasites. These pathways also demonstrate notable heterogeneity among parasites, suggesting that the metabolism of Sulfur-Containing Amino Acids reflects the diversity of parasitism among parasite species, and probably influences their biology and pathophysiology such as virulence competence and stress defense.
Haruhiko Toyohara - One of the best experts on this subject based on the ideXlab platform.
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Possible role of a taurine transporter in the deep-sea mussel Bathymodiolus septemdierum in adaptation to hydrothermal vents.
FEBS letters, 2008Co-Authors: Koji Inoue, Masatomi Hosoi, Kimihiko Tsukuda, Tomoko Koito, Yoshiko Miyazaki, Ryusuke Kado, Nobuyuki Miyazaki, Haruhiko ToyoharaAbstract:Various invertebrates inhabiting hydrothermal vents possess sulfur-oxidizing bacteria in their tissues; however, the mechanisms by which toxic sulfides are delivered to these endosymbionts remain unknown. Recently, detoxification of sulfides using thiotaurine, a Sulfur-Containing Amino Acid, has been suggested. In this study, we propose the involvement of a taurine transporter in sulfide detoxification in the deep-sea mussel Bathymodiolus septemdierum by demonstrating: (i) the abundance of its mRNA in the gill; (ii) its activity under a wide range of salinities; (iii) its low Michaelis constant value in taurine transportation; and (iv) its affinity for thiotaurine and the thiotaurine precursor, hypotaurine.
