• 제목/요약/키워드: Metabolism Modification

검색결과 103건 처리시간 0.021초

Deregulation of Aspartokinase by Single Nucleotide Exchange Leads to Global Flux Rearrangement in the Central Metabolism of Corynebacterium glutamicum

  • Kim Hyung-Min;Heinzle Elmar;Wittmann Christoph
    • Journal of Microbiology and Biotechnology
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    • 제16권8호
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    • pp.1174-1179
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    • 2006
  • The wild-type Corynebacterium glutamicum ATIC 13032 and Corynebacterium glutamicum ATTC 13032 lysC S301Y, exhibiting a deregulated aspartokinase, were compared concerning growth, lysine production, and intracellular carbon fluxes. Both strains differ by only one single nucleotide over the whole genome. In comparison to the wild-type, the mutant showed significant production of lysine with a molar yield of 0.087 mol (mol glucose$^{-1}$) whereas the biomass yield was reduced. The deregulation of aspartokinase further led to a global rearrangement of carbon flux throughout the whole central metabolism. This involved an increased flux through the pentose phosphate pathway (PPP) and an increased flux through anaplerosis. Because of this, the mutant revealed an enhanced supply of NADPH and oxaloacetate required for lysine biosynthesis. Additionally, the lumped flux through phosphoenolpyruvate carboxykinase and malic enzyme, withdrawing oxaloacetate back to the glycolysis and therefore detrimental for lysine production, was increased. The reason for this might be a contribution of malic enzyme to NADPH supply in the mutant in the mutant. The observed complex changes are remarkable, because they are due to the minimum genetic modification possible, the exchange of only one single nucleotide.

Polyunsaturated Fatty Acids in Male Ruminant Reproduction - A Review

  • Tran, Len Van;Malla, Bilal Ahmad;Kumar, Sachin;Tyagi, Amrish Kumar
    • Asian-Australasian Journal of Animal Sciences
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    • 제30권5호
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    • pp.622-637
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    • 2017
  • Fatty acids such as n-3 and n-6 polyunsaturated fatty acids (PUFA) are critical nutrients, used to improve male reproductive performance through modification of fatty acid profile and maintenance of sperm membrane integrity, especially under cold shock or cryopreservation condition. Also, PUFA provide the precursors for prostaglandin synthesis and can modulate the expression patterns of many key enzymes involved in both prostaglandin and steroid metabolism. Many studies carried out on diets supplemented with PUFA have demonstrated their capability to sustain sperm motility, viability and fertility during chilling and freezing as well as improving testis development and spermatogenesis in a variety of livestock species. In addition to the type and quantity of dietary fatty acids, ways of addition of PUFA to diet or semen extender is very crucial as it has different effects on semen quality in male ruminants. Limitation of PUFA added to ruminant ration is due to biohydrogenation by rumen microorganisms, which causes conversion of unsaturated fatty acids to saturated fatty acids, leading to loss of PUFA quantity. Thus, many strategies for protecting PUFA from biohydrogenation in rumen have been developed over the years. This paper reviews four aspects of PUFA in light of previous research including rumen metabolism, biological roles, influence on reproduction, and strategies to use in male ruminants.

Gene-Diet Interaction on Cancer Risk in Epidemiological Studies

  • Lee, Sang-Ah
    • Journal of Preventive Medicine and Public Health
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    • 제42권6호
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    • pp.360-370
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    • 2009
  • Genetic factors clearly play a role in carcinogenesis, but migrant studies provide unequivocal evidence that environmental factors are critical in defining cancer risk. Therefore, one may expect that the lower availability of substrate for biochemical reactions leads to more genetic changes in enzyme function; for example, most studies have indicated the variant MTHFR genotype 677TT is related to biomarkers, such as homocysteine concentrations or global DNA methylation particularly in a low folate diet. The modification of a phenotype related to a genotype, particularly by dietary habits, could support the notion that some of inconsistencies in findings from molecular epidemiologic studies could be due to differences in the populations studied and unaccounted underlying characteristics mediating the relationship between genetic polymorphisms and the actual phenotypes. Given the evidence that diet can modify cancer risk, gene-diet interactions in cancer etiology would be anticipated. However, much of the evidence in this area comes from observational epidemiology, which limits the causal inference. Thus, the investigation of these interactions is essential to gain a full understanding of the impact of genetic variation on health outcomes. This report reviews current approaches to gene-diet interactions in epidemiological studies. Characteristics of gene and dietary factors are divided into four categories: one carbon metabolism-related gene polymorphisms and dietary factors including folate, vitamin B group and methionines; oxidative stress-related gene polymorphisms and antioxidant nutrients including vegetable and fruit intake; carcinogen-metabolizing gene polymorphisms and meat intake including heterocyclic amins and polycyclic aromatic hydrocarbon; and other gene-diet interactive effect on cancer.

A Review on Metabolic Pathway Analysis with Emphasis on Isotope Labeling Approach

  • Azuyuki, Shimizu
    • Biotechnology and Bioprocess Engineering:BBE
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    • 제7권5호
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    • pp.237-251
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    • 2002
  • The recent progress on metabolic systems engineering was reviewed based on our recent research results in terms of (1) metabolic signal flow diagram approach, (2) metabolic flux analysis (MFA) in particular with intracellular isotopomer distribution using NMR and/or GC-MS, (3) synthesis and optimization of metabolic flux distribution (MFD), (4) modification of MFD by gene manipulation and by controlling culture environment, (5) metabolic control analysis (MCA), (6) design of metabolic regulation structure, and (7) identification of unknown pathways with isotope tracing by NMR. The main characteristics of metabolic engineering is to treat metabolism as a network or entirety instead of individual reactions. The applications were made for poly-3-hydroxybutyrate (PHB) production using Ralstonia eutropha and recombinant Escherichia coli, lactate production by recombinant Saccharomyces cerevisiae, pyruvate production by vitamin auxotrophic yeast Toluropsis glabrata, lysine production using Corynebacterium glutamicum, and energetic analysis of photosynthesic microorganisms such as Cyanobateria. The characteristics of each approach were reviewed with their applications. The approach based on isotope labeling experiments gives reliable and quantitative results for metabolic flux analysis. It should be recognized that the next stage should be toward the investigation of metabolic flux analysis with gene and protein expressions to uncover the metabolic regulation in relation to genetic modification and/ or the change in the culture condition.

An Essential Histidine Residue in the Catalytic Mechanism of the Rat Kidney γ-Glutamyl Transpeptidase

  • Kim, Soo-Ja;Ko, Moon-Kyu;Chai, Kyu-Yun;Cho, Seong-Wan;Lee, Woo-Yiel
    • Bulletin of the Korean Chemical Society
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    • 제28권2호
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    • pp.271-275
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    • 2007
  • γ -Glutamyl transpeptidase (EC 2.3.2.2) plays a key role in glutathione metabolism by catalyzing the transfer of the γ -glutamyl residue and hydrolysis of glutathione. The functional residues at the active site of the rat kidney γ -glutamyl transpeptidase were investigated by kinetic studies at various pH, the treatment of diethylpyrocarbonate (DEPC), and photooxidation in presence of methylene blue. An ionizable group affecting the enzymatic activity with an apparent pKa value of 7.1, which is in the range of pKa values for a histidine residue in protein, was obtained by examining the pH-dependence of kinetic parameters. The pH effect on the photoinduced inactivation rate of the enzyme corresponds to that expected for the photooxidation of the free histidine. The involvement of a histidine in the catalytic site of the enzyme was further supported by DEPC modification accompanied by an increase in absorbance at 240 nm, indicating the formation of Ncarbethoxyhistidine. The histidine located at the position of 382 in the precursor of the enzyme is primarily suspected based on the amino acid sequence alignment of the transpeptidases from various organisms.

Gene Microarray Assessment of Multiple Genes and Signal Pathways Involved in Androgen-dependent Prostate Cancer Becoming Androgen Independent

  • Liu, Jun-Bao;Dai, Chun-Mei;Su, Xiao-Yun;Cao, Lu;Qin, Rui;Kong, Qing-Bo
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권22호
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    • pp.9791-9795
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    • 2014
  • To study the gene expression change and possible signal pathway during androgen-dependent prostate cancer (ADPC) becoming androgen-independent prostate cancer (AIPC), an LNCaP cell model of AIPC was established using flutamide in combination with androgen-free environment inducement, and differential expression genes were screened by microarray. Then the biological process, molecular function and KEGG pathway of differential expression genes are analyzed by Molecule Annotation System (MAS). By comparison of 12,207 expression genes, 347 expression genes were acquired, of which 156 were up-ragulated and 191 down-regulated. After analyzing the biological process and molecule function of differential expression genes, these genes are found to play crucial roles in cell proliferation, differntiation, cell cycle control, protein metabolism and modification and other biological process, serve as signal molecules, enzymes, peptide hormones, cytokines, cytoskeletal proteins and adhesion molecules. The analysis of KEGG show that the relevant genes of AIPC transformation participate in glutathione metabolism, cell cycle, P53 signal pathway, cytochrome P450 metabolism, Hedgehog signal pathway, MAPK signal pathway, adipocytokines signal pathway, PPAR signal pathway, TGF-${\beta}$ signal pathway and JAK-STAT signal pathway. In conclusion, during the process of ADPC becoming AIPC, it is not only one specific gene or pathway, but multiple genes and pathways that change. The findings above lay the foundation for study of AIPC mechanism and development of AIPC targeting drugs.

Characterization of a novel posttranslational modification in polypyrimidine tract-binding proteins by SUMO1

  • Han, Wei;Wang, Lin;Yin, Bin;Peng, Xiaozhong
    • BMB Reports
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    • 제47권4호
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    • pp.233-238
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    • 2014
  • Polypyrimidine tract-binding protein 1 (PTBP1) and its brain-specific homologue, PTBP2, are associated with pre-mRNAs and influence pre-mRNA processing, as well as mRNA metabolism and transport. They play important roles in neural differentiation and glioma development. In our study, we detected the expression of the two proteins in glioma cells and predicted that they may be sumoylated using SUMOplot analyses. We confirmed that PTBP1 and PTBP2 can be modified by SUMO1 with co-immunoprecipitation experiments using 293ET cells transiently co-expressing SUMO1 and either PTBP1 or PTBP2. We also found that SUMO1 modification of PTBP2 was enhanced by Ubc9 (E2). The mutation of the sumoylation site (Lys137) of PTBP2 markedly inhibited its modification by SUMO1. Interestingly, in T98G glioma cells, the level of sumoylated PTBP2 was reduced compared to that of normal brain cells. Overall, this study shows that PTBP2 is posttranslationally modified by SUMO1.

12주 동안의 저열량식사와 행동수정요법이 비만여성의 체격지수와 생화학적 영양상태에 미치는 영향 (Effect of 12-week Low Calorie Diet and Behavior Modification on the Anthropomeric Indices and Biochemical Nutritional Status of Obese Woman)

  • 손숙미;김희준
    • 대한지역사회영양학회지
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    • 제10권4호
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    • pp.525-535
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    • 2005
  • This study was conducted to investigate the effect of a 3 week low calorie diet (LCD) and a 9 week of behavior modification (BM) program on the weight loss, mineral and vitamin status in 22 obese women. The subject were healthy, obese (PIBW> $120\%$) women aged 20 - 50 Yr and not taking any medications known to influence body composition, mineral or vitamin metabolism During the LCD program, subjects were provided commercial liquid formulas with 125 kcal per pack and were instructed to have a formula for replacement of one meal and at least one regular meal per day within the range of daily 800 - 1200 kcal intake. During the BM program the subjects weekly attended the group nutrition counseling session to encourage themselves to modify their eating behavior and spontaneously restrict their energy intakes. The BM program focused on stimulus control, control of portion sizes and modification of binge eating and other adverse habits. The initial mean energy intake of subjects was 2016.9 $\pm$ 129.8 kcal ($100.8\%$ of RDA) and dropped to 1276.5 $\pm$ 435.7 kcal at the end of a 3 week of LCD program and elevated to 1762 $\pm$ 329.3 kcal at the end of a 9 week of BM program. Carbohydrate, protein and fat intakes were significantly decreased at the end of the LCD but carbohydrate was the only macro nutrient that showed significant decrease (p < 0.05) at the end of the BM program compared to baseline. Calcium and iron intakes decreased significantly (p < 0.01, respectively) with no significant changes in other micronutrients at the end of the LCD. The mean weight of the subjects decreased from 73.8 $\pm$ 8.0 kg to 69.2 $\pm$ 7.7 kg with LCD and ended up with 67.7 $\pm$ 7.1 kg after 9 weeks of BM. The 3 weeks of LCD reduced most of the anthropometric indices such as BMI, PIBW, fat weight, wast-to-hip ratio and subscapular and suprailiac skinfold thickness. The 9 weeks of behavior modification showed slight change or maintenance of each anthropometric measurements. Weight loss and decreased WHR with the diet program induced significantly decreased systolic blood pressure. SGOT, SGPT and serum insulin levels with improved serum lipid profiles. Biochemical parameters related to iron status such as hemoglobin, hematocrit were significantly decreased (p < 0.01) at the end of the LCD. But their mean values were within normal range. The mean serum 25 (OH) vitamin $D_3$ level significantly increased after whole diet program. Serum folate level significantly decreased after 12 weeks of diet program. In conclusion 3 weeks of LCD brought 4.6 kg reduction in body weight without risk of iron, zinc or vitamin D deficiency and 9 weeks of the BM was effective to maintain nutritional status with slightly more weight reduction (1.5 kg). However calcium intake and serum folate should be monitored during the LCD and BM because of increased risk of deficiencies.

Study on the variation of cellular physiology of Escherichia coli during high cell density cultivation using 2-dimensional gel electrophoresis

  • 윤상선;이상엽
    • 한국생물공학회:학술대회논문집
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    • 한국생물공학회 2000년도 춘계학술발표대회
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    • pp.219-222
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    • 2000
  • Physiological changes of Escherichia coli during the fed-batch fermentation process were characterized in this study. Overall cellular protein samples prepared at the different stage of fermentation were separated by 2-dimensional gel electrophoresis (2-DE), and differently expressed 15 proteins, Phosphotransferase enzyme I, GroEL, Trigger factor, ${\beta}$ subunit of ATP synthase, Transcriptional regulator KDGR, Phosphoglycerate mutase 1, Inorganic pyrophosphatase, Serine Hydroxymethyl-transferase, ${\alpha}$ subunit of RNA polymerase, Elongation factor Tu, Elongation factor Ts, Tyrosine-tRNA ligase, DnaK suppressor protein, Transcriptional elongation factor, 30S ribosomal protein S6 were identified using matrix-assisted laser desorption / ionization time-of-flight mass spectrometry (MALDI-TOF MS). When bacterial cells grow to high cell density, and IPTG-inducible heterologous protein is produced, expression level of overall cellular proteins was decreased. According to their functions in the cell, identified proteins were classified into three groups, proteins involved in transport process, small-molecule metabolism, and synthesis and modification of macromolecules.

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Characteristics of 14-3-3 Proteins and Their Role in Plant Immunity

  • Oh, Chang-Sik
    • The Plant Pathology Journal
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    • 제26권1호
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    • pp.1-7
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    • 2010
  • Phosphorylation is a major post-translational modification of proteins that regulate diverse signal transduction pathways in eukaryotic cells. 14-3-3 proteins are regulatory proteins that bind to target proteins in a phosphorylation-dependent manner and have been shown to play an important role in plant growth and development, primary metabolism, and signal transduction. Because phosphorylation plays a critical role in signal transduction pathways to trigger plant immunity, involvement of 14-3-3 proteins in plant immunity has been suggested for a long time. Recent studies have provided new evidence to support a role for 14-3-3 proteins in plant immunity. This review will briefly discuss general characteristics of 14-3-3 proteins and their involvement in plant immunity.