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METABOLIC PATHWAYS --- ISOTOPE INDICATORS

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Molecular hydrogen (H2) has emerged as a promising therapeutic and preventive medical gas. Hydrogen gas has garnered significant attention in recent years due to its remarkable antioxidant and anti-inflammatory properties. H2 exhibits exceptional pharmacokinetics, swiftly traversing cellular biomembranes to access subcellular organelles indirectly regulating hormones and cytokines through various signal transduction pathways. H2 has the potential to address a wide range of issues, including clinical medical treatment in the areas of healthcare: myocardial ischemia, heart failure, cardiac arrest, metabolic syndrome, advanced-stage cancer, inflammatory diseases, Alzheimer's dementia, aging-related disorders, sports activities, and even beauty, agriculture, etc. Selected world-known authors in the field provide readers with a comprehensive overview of molecular hydrogen's remarkable effects and its physical, chemical, and therapeutic properties and potential in biomedical applications. This contributed volume fills the current gap in information and is intended for everyone who wants to be better informed about the wide possibilities of using molecular hydrogen. However, it is mainly intended for use by medical students, physiologists, pharmacologists, physicians, and other healthcare personnel who can use molecular hydrogen to improve the health of everyone who needs it.

Clinical biochemistry. --- Biochemistry. --- Metabolism. --- Cell biology. --- Cytology. --- Inflammation. --- Medical Biochemistry. --- Metabolic Pathways. --- Cell Biology. --- Hydrogen.

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More than 100 years ago, Dr Casimir Funk suggested the existence of a family of organic substances that are essential for life and thus introduced the concept of “vital amines” as essential nutrients with a specific action, requiring only minute amount with the power to cure a specific disease. Vitamins essential for human health are grouped according to whether they are soluble in water (hydrophilic) or in non-polar solvents (lipophilic). The hydrophilic vitamins are vitamin C and a series known as the vitamin B complex. Vitamin C is a reducing agent, whereas the vitamin B series are components of coenzymes. For example, riboflavin (vitamin B2) is a precursor of flavin adenine dinucleotide (FAD) and pantothenate (vitamin B5) is a component of coenzyme A. Indeed, several coenzymes contain a vitamin as part of their structure; this relation is undoubtedly responsible for creating an “essential” role for the vitamin. Since vitamins are involved in a wide range of biological processes and cell function, these are considered as essential nutrients. The essential nature of vitamins as well as their unique biochemistry, molecular mechanisms and cellular function in health and disease are emphasized in this book which will serve as a highly useful resource for health professionals, nutritional scientists, medical students, fellows, residents, and graduate students.

Clinical biochemistry. --- Biochemistry. --- Metabolism. --- Cell biology. --- Cytology. --- Neurosciences. --- Medical Biochemistry. --- Metabolic Pathways. --- Cell Biology. --- Neuroscience.

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Streptomycetes have become attractive hosts for heterologous protein production due to for instance, their ability to efficiently secrete their proteins in the extracellular environment. Among these microbes, Streptomyces lividans, known to have a reduced restriction-modification barrier, has been used more extensively for heterologous protein production. Hitherto, studies on metabolic characterization and engineering of S. lividans for heterologous protein production are limited, and of these, few are performed in (upscale) controlled fermentation environments. Without metabolomics, the metabolic impact/load that heterologous protein production exerts on the central carbon metabolism of S. lividans remains loosely understood, and can not easily be relieved.Therefore, the general objective of this dissertation was to characterize the growth and metabolism of S. lividans producing heterologous proteins in (upscale) controlled fermentation environments. The study is further extended to assess the effect of overexpressing the gene (pck) encoding phosphoenolpyruvate carboxykinase on heterologous protein production in S. lividans. A genome scale metabolic network model of wild-type S. lividans was extended to include mouse tumor necrosis factor-alpha (mTNF-alpha) production. The resulting model matrix was mathematically analyzed to check for its inherent properties and sensitivity to key measurable fluxes. Results obtained showed that model sensitivity to mTNF-alpha was tenfold higher than biomass production, while the latter was at least tenfold more sensitive than the measurable amino acid fluxes. Metabolic characterization of recombinant S. lividans, in comparison with the wild-type S. lividans, was done to assess metabolic impact based on both extracellular metabolomics and constraint-based modeling. Results obtained showed that the metabolic impact due to heterologous protein production results in lower substrate uptake and slower growth, the former an indication for metabolic channeling. The metabolic impact is widely-distributed in the genome of S. lividans, causing a great shift in its performance. Critical exchange fluxes in the recombinant cell’s or model’s performance have been identified as biomass, mTNF-alpha, histidine, valine and alanine. Finally, based on metabolic engineering techniques, it was revealed that pck overexpression in S. lividans TK24 results in up to 1.7-fold increase in hTNF-alpha production. The major findings in this dissertation are an indication of metabolic shifts within the recombinant cell as well as a positive correlation between the explored metabolic engineering approach and heterologous protein production.

academic collection --- 579.873.71 --- 577.121 --- Streptomyces --- General aspects of metabolism. Metabolic pathways. Metabolites. Anabolism. Catabolism --- Theses --- 577.121 General aspects of metabolism. Metabolic pathways. Metabolites. Anabolism. Catabolism --- 579.873.71 Streptomyces

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This book helps readers discover the forefront of personalized medicine on clinical metabolomics and its applications in genetic diseases. This comprehensive guide offers a functional relationship map between cell components and genetic variations in various diseases, providing insights that can be applied to personalized medicine. The book covers the latest developments in metabolomics for health, with practical guidance for clinical experts looking to advance their laboratory techniques and career. The metabolomics profile is a powerful tool that has revolutionized our understanding of the relationship between genetics, clinical readouts, and disease outcomes. By integrating metabolomics with genomics and clinical phenotypes, the authors have developed diagnostic and prediction models that have vastly improved patient outcomes and deepened the understanding of disease mechanisms. This model has been successfully applied in various conditions, including inborn errors of metabolism, primary immunodeficiency, and endocrine disorders. However, integrating metabolomics with other omics datasets and clinical phenotypes requires careful study design, analytical tools, and data analysis and interpretation. This groundbreaking new book provides essential guidance for researchers, students, and professionals looking to leverage metabolomics in their own work, including biochemical and clinical geneticists, pharmacogenomics and pharmacometabolomics experts, pharmaceutics and diagnostic researchers, medical scientists, clinical dietitians, metabolic engineers, clinical chemists, and personalized medicine specialists. .

Medical genetics. --- Metabolism --- Biochemistry. --- Metabolism. --- Cell biology. --- Medicine. --- Bioinformatics. --- Clinical Genetics. --- Metabolic Disease. --- Metabolic Pathways. --- Clinical Medicine. --- Disorders. --- Cytology.