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Methods in Molecular Biology (Clifton,... 2021Mitochondria play a central role in metabolic reprograming that occurs in numerous disease conditions. A precise evaluation of the extent of mitochondrial involvement in...
Mitochondria play a central role in metabolic reprograming that occurs in numerous disease conditions. A precise evaluation of the extent of mitochondrial involvement in the metabolic alterations is essential for a better definition of metabolically based therapeutic strategies. In this chapter, some simple protocols are presented, using carbon 13 tracers and nuclear magnetic resonance isotopomer analysis, for the evaluation of mitochondrial contributions to intermediary metabolism and the metabolic effects of the implementation of some mitochondrial regulatory mechanisms.
Topics: Animals; Carbon-13 Magnetic Resonance Spectroscopy; Cell Fractionation; Cells, Cultured; Energy Metabolism; Glutamine; Glycolysis; Humans; Mitochondria; Oxidative Phosphorylation
PubMed: 34096007
DOI: 10.1007/978-1-0716-1433-4_14 -
Journal of Applied Microbiology Jul 2015Ethanol production directly from CO2 , utilizing genetically engineered photosynthetic cyanobacteria as a biocatalyst, offers significant potential as a renewable and... (Review)
Review
Ethanol production directly from CO2 , utilizing genetically engineered photosynthetic cyanobacteria as a biocatalyst, offers significant potential as a renewable and sustainable source of biofuel. Despite the current absence of a commercially successful production system, significant resources have been deployed to realize this goal. Utilizing the pyruvate decarboxylase from Zymomonas species, metabolically derived pyruvate can be converted to ethanol. This review of both peer-reviewed and patent literature focuses on the genetic modifications utilized for metabolic engineering and the resultant effect on ethanol yield. Gene dosage, induced expression and cassette optimizat-ion have been analyzed to optimize production, with production rates of 0·1-0·5 g L(-1) day(-1) being achieved. The current 'toolbox' of molecular manipulations and future directions focusing on applicability, addressing the primary challenges facing commercialization of cyanobacterial technologies are discussed.
Topics: Autotrophic Processes; Biofuels; Cyanobacteria; Ethanol; Industrial Microbiology; Photosynthesis
PubMed: 25865951
DOI: 10.1111/jam.12821 -
Yakugaku Zasshi : Journal of the... 2017Since more than 70% of clinically used drugs are excreted from the body through metabolic processes, drug metabolism is a key determinant of pharmacokinetics, drug... (Review)
Review
Since more than 70% of clinically used drugs are excreted from the body through metabolic processes, drug metabolism is a key determinant of pharmacokinetics, drug response and drug toxicity. Much progress has been made in understanding drug-drug interactions via the inhibition or induction of cytochrome P450s (P450, CYP), as well as the effects of genetic polymorphisms of P450s on pharmacokinetics, and this has facilitated the progress of optimized pharmacotherapy in the clinic. Now, similar information is needed for non-CYP enzymes, especially concerning Phase I enzymes, based on advanced basic and clinical studies. Recently, it was revealed that post-transcriptional regulation by microRNAs or RNA editing plays a significant role in regulating the expression of drug-metabolizing enzymes, thus conferring variability in the detoxification and metabolic activation of drugs or chemicals. Changes in the expression profile of microRNAs in tissues or body fluids can be a biomarker of drug response and toxicity; therefore, such studies could also be useful for drug repositioning. In addition, microRNAs are involved in pharmacogenetics, because single nucleotide polymorphisms in microRNA binding sites of mRNAs, or microRNAs themselves, may cause changes in gene expression. Some microRNA-related polymorphisms could be biomarkers of the clinical outcome of pharmacotherapy. In this review article, recent progress and future directions for drug metabolism studies are discussed.
Topics: Binding Sites; Cytochrome P-450 Enzyme System; Drug Interactions; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Humans; Inactivation, Metabolic; MicroRNAs; Pharmaceutical Preparations; Pharmacogenetics; Pharmacokinetics; Polymorphism, Genetic; Polymorphism, Single Nucleotide; RNA Editing; RNA Processing, Post-Transcriptional
PubMed: 28566576
DOI: 10.1248/yakushi.16-00250-5 -
International Journal of Food Sciences... Sep 2014The demand for light beers has led brewers to innovate by developing light beer. However, these products are not widely accepted in Europe compared to North America and... (Review)
Review
The demand for light beers has led brewers to innovate by developing light beer. However, these products are not widely accepted in Europe compared to North America and Australasia because of their lack of fullness in the taste and low bitterness compared with conventional beer. The lower levels of some important compounds, present in light beer, can explain these features since they are responsible for the characteristics of the beer. These include alcohol soluble proteins, oligosaccharides, glycerol, polyphenols, iso-α-acids, fusel alcohols and trihydroxy fatty acids. Light beer is produced by several methods, the most commonly used is the addition of glucoamylase to the wort before or during fermentation. This enzyme metabolizes residual carbohydrates (mainly dextrins) transforming them into fermentable sugars and reducing the caloric and alcohol content in this type of beer. Recently pilot studies have been carried out with genetically engineered yeast strains in which amylolytic genes are introduced into the yeast genome in order to metabolize carbohydrate residues. When introducing amylolytic genes, a better fermentability occurs although the fullness of flavor still becomes reduced.
Topics: Amylases; Beer; Dietary Carbohydrates; Ethanol; Fermentation; Food Industry; Humans; Organisms, Genetically Modified; Taste; Yeasts
PubMed: 24601667
DOI: 10.3109/09637486.2014.893285 -
Yakugaku Zasshi : Journal of the... 2019Human hepatocytes possess a wider range of phase I and II drug-metabolizing enzyme activities than other liver tissue-derived products, such as human liver microsomes.... (Review)
Review
Human hepatocytes possess a wider range of phase I and II drug-metabolizing enzyme activities than other liver tissue-derived products, such as human liver microsomes. Thus, hepatocytes may be useful for predicting the in vivo metabolic fate of new drugs of abuse in humans. Recently, new types of human hepatocytes have been made commercially available for use in drug metabolism studies, such as a liver tumor-derived cell line (HepaRG), and a human induced pluripotent stem cell-derived hepatocyte (h-iPS-HEP). In our laboratory, HepaRG has been used to elucidate the metabolic pathways of XLR-11, a synthetic cannabinoid, and its thermal degradant. In addition, the potential of h-iPS-HEP to metabolize drugs was assessed using fentanyl as a model drug, and indeed, h-iPS-HEP exhibited a pattern for fentanyl metabolite formation similar to that observed in vivo. In addition, the phase I and II drug-metabolizing enzyme activities of HepaRG, h-iPS-HEP, liver-humanized mouse-derived hepatocytes (PXB-cellsTM), and human primary hepatocytes were evaluated and compared. HepaRG showed high phase I and II drug metabolism activities; however, the CYP2D6 activity in these cells was quite low, and therefore h-iPS-HEP lacked O-methylation and conjugation activities. PXB-cells provided optimal results, i.e., these cells are extremely easy to use, and they possess higher phase I and II drug-metabolizing enzyme activities than the other cells tested. Although PXB-cells are contaminated with mouse-derived cells up to a concentration of several percent, this cell system appears to be promising for the prediction of in vivo human metabolism of new drugs of abuse.
Topics: Animals; Cannabinoids; Cell Line; Cytochrome P-450 CYP2D6; Fentanyl; Hepatocytes; Humans; Methylation; Mice; Substance-Related Disorders
PubMed: 31061338
DOI: 10.1248/yakushi.18-00166-3 -
Environmental Science and Pollution... Jul 2023Contamination of soil and natural water bodies driven by increased organic pollutants remains a universal concern. Naturally, organic pollutants contain carcinogenic and... (Review)
Review
Contamination of soil and natural water bodies driven by increased organic pollutants remains a universal concern. Naturally, organic pollutants contain carcinogenic and toxic properties threatening all known life forms. The conventional physical and chemical methods employed to remove these organic pollutants ironically produce toxic and non-ecofriendly end-products. Whereas microbial-based degradation of organic pollutants provides an edge, they are usually cost-effective and take an eco-friendly approach towards remediation. Bacterial species, including Pseudomonas, Comamonas, Burkholderia, and Xanthomonas, have the unique genetic makeup to metabolically degrade toxic pollutants, conferring their survival in toxic environments. Several catabolic genes, such as alkB, xylE, catA, and nahAc, that encode enzymes and allow bacteria to degrade organic pollutants have been identified, characterized, and even engineered for better efficacy. Aerobic and anaerobic processes are followed by bacteria to metabolize aliphatic saturated and unsaturated hydrocarbons such as alkanes, cycloalkanes, aldehydes, and ethers. Bacteria use a variety of degrading pathways, including catechol, protocatechuate, gentisate, benzoate, and biphenyl, to remove aromatic organic contaminants such as polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and pesticides from the environment. A better understanding of the principle, mechanisms, and genetics would be beneficial for improving the metabolic efficacy of bacteria to such ends. With a focus on comprehending the mechanisms involved in various catabolic pathways and the genetics of the biotransformation of these xenobiotic compounds, the present review offers insight into the various sources and types of known organic pollutants and their toxic effects on health and the environment.
Topics: Environmental Pollutants; Biodegradation, Environmental; Bacteria; Hydrocarbons; Biotransformation; Polycyclic Aromatic Hydrocarbons; Soil Pollutants
PubMed: 37330441
DOI: 10.1007/s11356-023-28130-7 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Sep 2023As specialized intracellular parasite, viruses have no ability to metabolize independently, so they completely depend on the metabolic mechanism of host cells. Viruses... (Review)
Review
As specialized intracellular parasite, viruses have no ability to metabolize independently, so they completely depend on the metabolic mechanism of host cells. Viruses use the energy and precursors provided by the metabolic network of the host cells to drive their replication, assembly and release. Namely, viruses hijack the host cells metabolism to achieve their own replication and proliferation. In addition, viruses can also affect host cell metabolism by the expression of auxiliary metabolic genes (AMGs), affecting carbon, nitrogen, phosphorus, and sulfur cycles, and participate in microbial-driven biogeochemical cycling. This review summarizes the effect of viral infection on the host's core metabolic pathway from four aspects: cellular glucose metabolism, glutamine metabolism, fatty acid metabolism, and viral AMGs on host metabolism. It may facilitate in-depth understanding of virus-host interactions, and provide a theoretical basis for the treatment of viral diseases through metabolic intervention.
Topics: Humans; Metabolic Networks and Pathways; Virus Diseases; Carbohydrate Metabolism; Host Microbial Interactions; Lipid Metabolism
PubMed: 37805838
DOI: 10.13345/j.cjb.220888 -
International Journal of Molecular... Feb 2021The metabolic microenvironment, comprising all soluble and insoluble nutrients and co-factors in the extracellular milieu, has a major impact on cancer cell... (Review)
Review
The metabolic microenvironment, comprising all soluble and insoluble nutrients and co-factors in the extracellular milieu, has a major impact on cancer cell proliferation and survival. A large body of evidence from recent studies suggests that tumor cells show a high degree of metabolic flexibility and adapt to variations in nutrient availability. Insufficient vascular networks and an imbalance of supply and demand shape the metabolic tumor microenvironment, which typically contains a lower concentration of glucose compared to normal tissues. The present review sheds light on the recent literature on adaptive responses in cancer cells to nutrient deprivation. It focuses on the utilization of alternative nutrients in anabolic metabolic pathways in cancer cells, including soluble metabolites and macromolecules and outlines the role of central metabolic enzymes conferring metabolic flexibility, like gluconeogenesis enzymes. Moreover, a conceptual framework for potential therapies targeting metabolically flexible cancer cells is presented.
Topics: Gluconeogenesis; Humans; Metabolic Networks and Pathways; Neoplasms; Signal Transduction; Tumor Microenvironment
PubMed: 33540663
DOI: 10.3390/ijms22031476 -
Lipids in Health and Disease May 2018Bile acids (BAs) are important regulatory factors of life activities, which are involved in the regulation of glucose, lipid and energy metabolisms, and closely... (Review)
Review
Bile acids (BAs) are important regulatory factors of life activities, which are involved in the regulation of glucose, lipid and energy metabolisms, and closely associated with intestinal hormones, microbiotas and energy balance. BAs abnormalities easily lead to inflammation and metabolic diseases, in turn, the progress of diseases could influence characteristics of BAs. Therefore, accurate detection of BAs contents is of great significance to disease prevention, diagnosis and treatment. At present, the most widely used enzymatic method in clinical practice is applicable to the detection of total bile acid (TBA). In laboratory research, different types of BAs can be accurately separated and quantified by liquid chromatography-mass spectrometry (LC-MS). The metabolic profiling of BAs based on detection technologies can completely and accurately monitor their types and contents, playing a crucial role in disease prevention, diagnosis and treatment. We herein reviewed the main detection technologies of BAs and the application of metabolic profiling in related diseases in recent years.
Topics: Animals; Bile Acids and Salts; Chromatography, Liquid; Energy Metabolism; Enzyme Assays; Gastrointestinal Microbiome; Humans; Inflammation; Lipid Metabolism; Mass Spectrometry; Metabolic Diseases; Metabolome
PubMed: 29792192
DOI: 10.1186/s12944-018-0774-9 -
Carbohydrate Polymers Jan 2023Hyaluronan is being investigated extensively as a biocompatible and biodegradable material for use in biomedical applications. While the derivatization of hyaluronan...
Hyaluronan is being investigated extensively as a biocompatible and biodegradable material for use in biomedical applications. While the derivatization of hyaluronan broadens its potential therapeutic use, the pharmacokinetics and metabolization of the derivatives must be thoroughly investigated. The fate of intraperitoneally-applied native and lauroyl-modified hyaluronan films with varying degrees of substitution was investigated in-vivo employing an exclusive stable isotope-labelling approach and LC-MS analysis. The materials were gradually degraded in peritoneal fluid, lymphatically absorbed, preferentially metabolized in the liver and eliminated without any observable accumulation in the body. Hyaluronan acylation prolongs its presence in the peritoneal cavity depending on the degree of substitution. The safety of acylated hyaluronan derivatives was confirmed via a metabolic study that revealed its degradation into non-toxic metabolites, i.e. native hyaluronan and free fatty acid. Stable isotope-labelling with LC-MS tracking comprises a high-quality procedure for the investigation of the metabolism and biodegradability of hyaluronan-based medical products in-vivo.
Topics: Hyaluronic Acid; Acylation; Chromatography, Liquid; Fatty Acids, Nonesterified; Isotopes
PubMed: 36876812
DOI: 10.1016/j.carbpol.2022.120201