• Title/Summary/Keyword: metabolic pathways

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Mass Spectrometry-based Hair Metabolomics for Biomarker Discovery

  • Lee, Yu Ra;Hong, Jongki;Chung, Bong Chul
    • Mass Spectrometry Letters
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    • v.13 no.1
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    • pp.2-10
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    • 2022
  • Metabolomics makes it possible to analyze the interrelationships between various signaling molecules based on the metabolic pathways involved by using high-resolution devices. This approach can also be used to obtain large-scale metabolic information to identify the relevant pathways for disease diagnosis and prognosis and search for potential biomarkers. In the fields of medicine and forensics, hair analysis is used to detect various metabolites in the body. Hair can be harvested readily in a noninvasive manner and is easier to transport and store than blood and urine. Another advantage from a forensic viewpoint is that hair reflects all the components of body fluids. In addition, because of the unique coating structure of hair, it can be used for measurements without changing or destroying its adsorbed components. In this review, the pretreatments for hair analysis, instrumental conditions and clinical applications are discussed. Especially, the clinical use of hair metabolomics in the diagnosis of various diseases and the limitations of the technique are described.

Characterization of in vitro Metabolites of Methylenedioxy Designer Drugs

  • Jun Sang Yu;So Young Jo;Il-Ho Park;Hye Hyun Yoo
    • Mass Spectrometry Letters
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    • v.14 no.1
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    • pp.1-8
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    • 2023
  • Eutylone, dibutylone, and dimethylone are potential psychotropic designer drugs. The purpose of this study was to investigate the in vitro metabolic pathways of synthetic cathinones with methylenedioxy groups. The three methylenedioxy derivatives were incubated with human liver microsomes. The metabolites were characterized based on liquid chromatography and quadrupole-time-of-flight mass spectrometry. Eutylone, dibutylone, and dimethylone were metabolized to yield three, six, and four metabolites, respectively. Reduction and demethylenation were the major metabolic pathways for all three drugs tested. However, dibutylone and dimethylone showed an additional metabolite generated via N-oxidation. These results provide evidence for the in vivo metabolism of methylenedioxy synthetic cathinones, and could be applied to the analysis of synthetic cathinones and their relevant metabolites in biological samples.

Evaluation of Recent Data Processing Strategies on Q-TOF LC/MS Based Untargeted Metabolomics

  • Kaplan, Ozan;Celebier, Mustafa
    • Mass Spectrometry Letters
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    • v.11 no.1
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    • pp.1-5
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    • 2020
  • In this study, some of the recently reported data processing strategies were evaluated and modified based on their capabilities and a brief workflow for data mining was redefined for Q-TOF LC-MS based untargeted metabolomics. Commercial pooled human plasma samples were used for this purpose. An ultrafiltration procedure was applied on sample preparation. Sample set was analyzed through Q-TOF LC/MS. A C18 column (Agilent Zorbax 1.8 µM, 50 × 2.1 mm) was used for chromatographic separation. Raw chromatograms were processed using XCMS - R programming language edition and Isotopologue Parameter Optimization (IPO) was used to optimize XCMS parameters. The raw XCMS table was processed using MS Excel to find reliable and reproducible peaks. Totally 1650 reliable and reproducible potential metabolite peaks were found based on the data processing procedures given in this paper. The redefined dataset was upload into MetaboAnalyst platform and the identified metabolites were matched with 86 metabolic pathways. Thus, two list were obtained and presented in this study as supplement files. The first list is to present the retention times and m/z values of detected metabolite peaks. The second list is the metabolic pathways related with the identified metabolites. The briefly described data processing strategies and dataset presented in this study could be beneficial for the researchers working on untargeted metabolomics for processing their data and validating their results.

AMPK Activators from Natural Products: A Patent Review

  • Uddin, Mohammad Nasir;Sharma, Govinda;Choi, Hong Seok;Lim, Seong-Il;Oh, Won Keun
    • Natural Product Sciences
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    • v.19 no.1
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    • pp.1-7
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    • 2013
  • AMP-activated protein kinase (AMPK) is a major cellular energy sensor and master regulator of metabolic homeostasis. On activation, this cellular fuel sensing enzyme induces a series of metabolic changes to balance energy consumption via multiple downstream signaling pathways controlling nutrient uptake and energy metabolism. This pivotal role of AMPK has led to the development of numerous AMPK activators which might be used as novel drug candidates in the treatment of AMPK related disorders, diabetes, obesity, and other metabolic diseases. Consequently, a number of patents have been published on AMPK activators from natural products and other sources. This review covers the patented AMPK activators from natural products and their therapeutic potential in treatment or prevention of metabolic diseases including diabetes and obesity.

Inherited Metabolic Disorders Involving the Nervous System (신경계 이상을 동반하는 선천성 대사 질환)

  • Jeesuk Yu
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.23 no.2
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    • pp.21-30
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    • 2023
  • Inherited metabolic disorders (IMD) are a group of disorders caused by defects in specific biochemical pathways. Up to 85% of IMD display predominantly neurological manifestations by affecting neurodevelopment or causing neurodegeneration. These neurometabolic disorders present with a variety of neurological and non-neurological manifestations. Early diagnosis of IMD is important because some disorders can be treated or improved with specific treatment if detected early. For prompt diagnosis and treatment, it is important to suspect IMD by being familiar with the clinical characteristics, biochemical abnormalities, and characteristic neuroimaging patterns that appear in IMD. Genetic testing, including next-generation sequencing, is also important in diagnosing IMD. During the follow-up of patients with IMD, it is necessary to conduct regular physical and neurological examinations in addition to disease-specific management.

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Congenital Metabolic Disorders with Cutaneous Changes (피부계 이상을 동반하는 선천성대사질환)

  • Sang Eun, Lee
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.22 no.2
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    • pp.53-57
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    • 2022
  • Congenital metabolic disorders are rare inherited disorders resulting from a defect in biochemical and metabolic pathways affecting proteins, fats, carbohydrates metabolism or impaired organelle function. Depending on the abnormality of biochemical metabolism, various precursors and their abnormal metabolites can accumulate in the body and the final products which are critical in normal physiology can be deficient, resulting in disease. Congenital metabolic disorders present complicated medical conditions involving several human organ systems, including nervous system, eyes, liver, and kidneys. Various proteins and lipids are involved in the development and homeostasis of the skin, so many congenital metabolic disorders present abnormal changes in skin and hair. In this review, congenital metabolic diseases related to amino acid and lipid metabolism accompanying skin abnormalities will be discussed.

Target Identification for Metabolic Engineering: Incorporation of Metabolome and Transcriptome Strategies to Better Understand Metabolic Fluxes

  • Lindley, Nic
    • Proceedings of the Korean Society for Applied Microbiology Conference
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    • 2004.06a
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    • pp.60-61
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    • 2004
  • Metabolic engineering is now a well established discipline, used extensively to determine and execute rational strategies of strain development to improve the performance of micro-organisms employed in industrial fermentations. The basic principle of this approach is that performance of the microbial catalyst should be adequately characterised metabolically so as to clearlyidentify the metabolic network constraints, thereby identifying the most probable targets for genetic engineering and the extent to which improvements can be realistically achieved. In order to harness correctly this potential, it is clear that the physiological analysis of each strain studied needs to be undertaken under conditions as close as possible to the physico-chemical environment in which the strain evolves within the full-scale process. Furthermore, this analysis needs to be undertaken throughoutthe entire fermentation so as to take into account the changing environment in an essentially dynamic situation in which metabolic stress is accentuated by the microbial activity itself, leading to increasingly important stress response at a metabolic level. All too often these industrial fermentation constraints are overlooked, leading to identification of targets whose validity within the industrial context is at best limited. Thus the conceptual error is linked to experimental design rather than inadequate methodology. New tools are becoming available which open up new possibilities in metabolic engineering and the characterisation of complex metabolic networks. Traditionally metabolic analysis was targeted towards pre-identified genes and their corresponding enzymatic activities within pre-selected metabolic pathways. Those pathways not included at the onset were intrinsically removed from the network giving a fundamentally localised vision of pathway functionality. New tools from genome research extend this reductive approach so as to include the global characteristics of a given biological model which can now be seen as an integrated functional unit rather than a specific sub-group of biochemical reactions, thereby facilitating the resolution of complexnetworks whose exact composition cannot be estimated at the onset. This global overview of whole cell physiology enables new targets to be identified which would classically not have been suspected previously. Of course, as with all powerful analytical tools, post-genomic technology must be used carefully so as to avoid expensive errors. This is not always the case and the data obtained need to be examined carefully to avoid embarking on the study of artefacts due to poor understanding of cell biology. These basic developments and the underlying concepts will be illustrated with examples from the author's laboratory concerning the industrial production of commodity chemicals using a number of industrially important bacteria. The different levels of possibleinvestigation and the extent to which the data can be extrapolated will be highlighted together with the extent to which realistic yield targets can be attained. Genetic engineering strategies and the performance of the resulting strains will be examined within the context of the prevailing experimental conditions encountered in the industrial fermentor. Examples used will include the production of amino acids, vitamins and polysaccharides. In each case metabolic constraints can be identified and the extent to which performance can be enhanced predicted

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Impact of glucose and pyruvate on adenosine triphosphate production and sperm motility in goats

  • Rangga Setiawan;Raden Febrianto Christi;Ken Ratu Gharizah Alhuur;Rini Widyastuti;Nurcholidah Solihati;Siti Darodjah Rasad;Kundrat Hidajat;Duy Ngoc Do
    • Animal Bioscience
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    • v.37 no.4
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    • pp.631-639
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    • 2024
  • Objective: This study evaluates goat sperm motility in response to metabolic substrates and various inhibitors, aiming to assess the relative contribution of glycolysis and mitochondrial oxidation for sperm movement and adenosine triphosphate (ATP) production. Methods: In the present study, two main metabolic substrates; 0 to 0.5 mM glucose and 0 to 30 mM pyruvate were used to evaluate their contribution to sperm movements of goats. Using a 3-chloro-1,2-propanediol (3-MCPD), a specific inhibitor for glycolysis, and carbonyl cyanide 3-chlorophenylhydrazone as an inhibitor for oxidative phosphorylation, cellular mechanisms into ATP-generating pathways in relation to sperm movements and ATP production were observed. Data were analysed using one-way analysis of variance for multiple comparisons. Results: Sperm motility analysis showed that either glucose or pyruvate supported sperm movement during 0 to 30 min incubation. However, the supporting effects were abolished by the addition of a glycolysis inhibitor or mitochondrial uncoupler, concomitant with a significant decrease in ATP production. Although oxidative phosphorylation produces larger ATP concentrations than those from glycolysis, sperm progressivity in relation to these two metabolic pathways is comparable. Conclusion: Based on the present study, we suggest that goat sperm use glucose and pyruvate to generate cellular energy through glycolysis and mitochondrial respiration pathways to maintain sperm movement.