• Title/Summary/Keyword: Metabolism Modification

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Post-Translational Modification of Proteins in Toxicological Research: Focus on Lysine Acylation

  • Lee, Sangkyu
    • Toxicological Research
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    • v.29 no.2
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    • pp.81-86
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    • 2013
  • Toxicoproteomics integrates the proteomic knowledge into toxicology by enabling protein quantification in biofluids and tissues, thus taking toxicological research to the next level. Post-translational modification (PTM) alters the three-dimensional (3D) structure of proteins by covalently binding small molecules to them and therefore represents a major protein function diversification mechanism. Because of the crucial roles PTM plays in biological systems, the identification of novel PTMs and study of the role of PTMs are gaining much attention in proteomics research. Of the 300 known PTMs, protein acylation, including lysine formylation, acetylation, propionylation, butyrylation, malonylation, succinylation, and crotonylation, regulates the crucial functions of many eukaryotic proteins involved in cellular metabolism, cell cycle, aging, growth, angiogenesis, and cancer. Here, I reviewed recent studies regarding novel types of lysine acylation, their biological functions, and their applicationsin toxicoproteomics research.

Systems Biology Studies and Metabolic Modification of Metabolites Producing Bacteria (대사산물 과량생산을 위한 미생물 균주의 시스템 생물학 연구 및 대사특성 개량)

  • Hong, Soon Ho
    • Korean Chemical Engineering Research
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    • v.45 no.6
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    • pp.529-535
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    • 2007
  • Recently, an attempt to analyze and modify metabolic networks of living organisms in global level emerged with the benefit of development of high-throughput techniques, and it is generally called systems biology. Various systems biology studies have been carried out for the development of enhanced metabolite production systems. By modification of metabolic characteristics of microorganisms, metabolite productivities and yields obtained with metabolically engineered bacteria increased significantly compare with that obtained with wild type bacteria.

Oxidative Modification of Cytochrome c by Tetrahydropapaveroline, an Isoquinoline-Derived Neurotoxin

  • Kang, Jung Hoon
    • Bulletin of the Korean Chemical Society
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    • v.34 no.2
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    • pp.406-410
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    • 2013
  • Tetrahyropapaveroline (THP) is compound derived from dopamine metabolism and is capable of causing dopaminergic neurodegenerative disorder, such as Parkinson's disease (PD). The aim of this study was to evaluate the potential of THP to cause oxidative damage on the structure of cytochrome c (cyt c). Our data showed that THP led to protein aggregation and the formation of carbonyl compound in protein aggregates. THP also induced the release of iron from cyt c. Reactive oxygen species (ROS) scavengers and iron specific chelator inhibited the THP-mediated cyt c modification and carbonyl compound formation. The results of this study show that ROS may play a critical role in THP-induced cyt c modification and iron releasing of cyt c. When cyt c that has been exposed to THP was subsequently analyzed by amino acid analysis, lysine, histidine and methionine residues were particularly sensitive. It is suggested that oxidative damage of cyt c by THP might induce the increase of iron content in cells and subsequently led to the deleterious condition. This mechanism is associated with the deterioration of organs under neurodegenerative disorder such as PD.

The Oxidative Modification of COL6A1 in Membrane Proteins of Ovarian Cancer Patients

  • Yang, Hee-Young;Lee, Tae-Hoon
    • Reproductive and Developmental Biology
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    • v.36 no.1
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    • pp.39-47
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    • 2012
  • Ovarian cancer is the most lethal gynecological malignancy, and specific biomarkers are important needed to improve diagnosis, prognosis, and to forecast and monitor treatment efficiency. There are a lot of pathological factors, including reactive oxygen species (ROS), involved in the process of cancer initiation and progression. The oxidative modification of proteins by ROS is implicated in the etiology or progression of disorders and diseases. In this study, a labeling experiment with the thiol-modifying reagent biotinylated iodoacetamide (BIAM) revealed that a variety of proteins were differentially oxidized between normal and tumor tissues of ovarian cancer patients. To identify cysteine oxidation-sensitive proteins in ovarian cancer patients, we performed comparative analysis by nano-UPLC-$MS^E$ shotgun proteomics. We found oxidation-sensitive 22 proteins from 41 peptides containing cysteine oxidation. Using Ingenuity program, these proteins identified were established with canonical network related to cytoskeletal network, cellular organization and maintenance, and metabolism. Among oxidation-sensitive proteins, the modification pattern of Collagen alpha-1(VI) chain (COL6A1) was firstly confirmed between normal and tumor tissues of patients by 2-DE western blotting. This result suggested that COL6A1 might have cysteine oxidative modification in tumor tissue of ovarian cancer patients.

P62 and the Sequestosome, a Novel Mechanism for Protein Metabolism

  • Shin, Jae-Kyoon
    • Archives of Pharmacal Research
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    • v.21 no.6
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    • pp.629-633
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    • 1998
  • In addition to selecting proteins for degradation by the 26S proteasome, ubiqitination appears to serve other regulatory functions, including for endosomal/lysosomal targeting, protein translocation, and enzyme modification. Currently, little is known how multiubiquitin chains are recognized by these cellular mechanisms. Within the 26S proteasome, one subunit (Mcb1/S5a) has been identified that has affinity for multiubiquitin chains and may function as a ubiquitin receptor. We recently found that a non-proteasomal protein p62 also preferentially binds multiubiquitin chains and forms a novel cytoplasmic structure "sequestosome" which serves as a storage place for ubiquitinated proteins. In the present manuscript, the role and regulation of p62 in relation to the sequestosomal function will be reviewed.

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Dynamically Modified Silica and its Applications in Drug Control and Drug Metabolism Studies

  • Hansen, Steen Honore;Helboe, Per;Thomsen, Morgens
    • Korean Journal of Pharmacognosy
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    • v.19 no.4
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    • pp.217-227
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    • 1988
  • An alternative to the well known reversed-phase separations on chemically-boned phases has been developed. The approach is based on a dynamic modification of bare silica with long chain quaternary ammonium ions. The influence of the concentration and type of quaternary ammonium ion, the pH value and the ionic strength of the eluent on the selectivity towards test solutes has been investigated. The large number of parameters that can be attained. Once established, a high degree of reproducibility of the selectivity between solutes is obtained even when using different brands of silica; this is in contrast to the situation when using chemically-bonded phases, such as for example, different brands of octadecylsilyl-bonded silica materials. Examples of the use of system in pharmaceutical analysis and drug metabolism studies are given.

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Glutamine Synthetase of some Fermentation Bacteria: Function and Application

  • Tachiki, Takashi
    • Proceedings of the Korean Society for Applied Microbiology Conference
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    • 1986.12a
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    • pp.506-508
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    • 1986
  • Metabolic activity of inorganic nitrogenous compounds affects not only microbial growth but also metabolite production in fermentation technology. We have worked on the enzymes participating in ammonia assimulation of some fermentation bacteria. This paper summarizes the results on glutamine synthetase and its application in practical field. Glutamine synthetase (L-glutamate:ammonia ligase, EC. 6.3.1.2) catalyzes the formation of glutamine from glutamate and ammonia at the expense of cleavage of ATP and inorganic phosphate. The enzyme plays a dual role in nitrogen metabolism in bacteria; it is a key enzyme not only in the biosynthesis of various compounds through glutamine but also in the regulation of synthesis of some enzymes involved in the metabolism of nitrogenous compounds. The detailed works with the Eschericia coli and other enterobacterial enzymes revealed that glutamine synthetase is controlled by the following complex of mechanisms: (a) feedback inhibition by end products, (b) repression and derepression of enzyme synthesis, (c) modulation of enzyme activity in response to divalent cation and (d) covalent modification of enzyme protein by adenylylation and its cascade control. Comparative studies have also been made on the enzymes from other organisms.

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1,8-cineole protected human lipoproteins from modification by oxidation and glycation and exhibited serum lipid-lowering and anti-inflammatory activity in zebrafish

  • Cho, Kyung-Hyun
    • BMB Reports
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    • v.45 no.10
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    • pp.565-570
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    • 2012
  • We recently reported that a water extract of laurel or turmeric, 1,8-cineole enriched fractions, showed hypolipidemic activity in the zebrafish model. Therefore, the present study investigated the cineole's anti-oxidant and anti-inflammatory activities in lipoprotein metabolism in vitro and in vivo. Cineole had inhibitory effects on cupric ion-mediated oxidation of lipoproteins in general, while simultaneously enhancing ferric ion removal ability in high-density lipoprotein (HDL). Hypercholesterolemia was induced in zebrafish using cholesterol-feeding treatment, 4% cholesterol, for 3 weeks. After feeding with or without the addition of cineole, the results revealed that cineole possessed lipid-lowering and anti-inflammatory activities in hypercholesterolemic zebrafish. In addition, serum amyloid A and interleukin-6 levels were lowered and lipid accumulation was decreased in the liver. Conclusively, 1,8-cineole was found to have anti-oxidant activities in lipoprotein metabolism both in vitro and in vivo with simultaneous reduction of lipid accumulation in the liver of zebrafish.

Human Transcriptome and Chromatin Modifications: An ENCODE Perspective

  • Shen, Li;Choi, Inchan;Nestler, Eric J.;Won, Kyoung-Jae
    • Genomics & Informatics
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    • v.11 no.2
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    • pp.60-67
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    • 2013
  • A decade-long project, led by several international research groups, called the Encyclopedia of DNA Elements (ENCODE), recently released an unprecedented amount of data. The ambitious project covers transcriptome, cistrome, epigenome, and interactome data from more than 1,600 sets of experiments in human. To make use of this valuable resource, it is important to understand the information it represents and the techniques that were used to generate these data. In this review, we introduce the data that ENCODE generated, summarize the observations from the data analysis, and revisit a computational approach that ENCODE used to predict gene expression, with a focus on the human transcriptome and its association with chromatin modifications.

Nitrogen Control in Corynebacterium glutamicum: Proteins, Mechanisms, Signals

  • Burkovski, Burkovski;Andreas, Andreas
    • Journal of Microbiology and Biotechnology
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    • v.17 no.2
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    • pp.187-194
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    • 2007
  • In order to utilize different nitrogen sources and to survive in a situation of nitrogen limitation, microorganisms have developed sophisticated mechanisms to adapt their metabolism to a changing nitrogen supply. In this communication, the recent knowledge of nitrogen regulation in the amino acid producer Corynebacterium glutamicum is summarized. The core adaptations of C. glutamicum to nitrogen limitation on the level of transcription are controlled by the global regulator AmtR. Further components of the signal pathway are GlnK, a $P_{II}-type$ signal transduction protein, and GlnD. Mechanisms involved in nitrogen control in C. glutamicum regulating gene expression and protein activity are repression of transcription, protein-complex formation, protein modification by adenylylation, change of intracellular localization, and proteolysis.