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  1. Marina Mohd Bakri
    MyJurnal
    Over the past decade, research involving immunometabolism, has been gaining much interest. The immune cell re-sponses of an individual may be influenced by metabolites released by the host or derived from the microbiota. How-ever, the immune response of an individual may vary depending on the health condition of an individual. During infection, the metabolic processes derived from the infectious diseases can effect the function of immune cells and thus determine the response or survival of the host during infection. Immunometabolism also has a role in tumor development although the mechanism of how tumor cells influence immune cell function is not well understood. Among the major meatbolic pathways that have been studied in immune cells include glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway, fatty acid oxidation, fatty acid synthesis and amino acid metabolism. Understanding the tight connection between metabolomics and immunity in health and disease will be crucial as this could lead to therapeutic interventions or in developing metabolomic biomarkers in immunology.
    Matched MeSH terms: Citric Acid Cycle
  2. Zhu W, Zheng W, Hu X, Xu X, Zhang L, Tian J
    Biochim Biophys Acta Proteins Proteom, 2017 Apr;1865(4):404-413.
    PMID: 28087425 DOI: 10.1016/j.bbapap.2017.01.004
    Lonicera japonica Thunb., also known as Jin Yin Hua and Japanese honeysuckle, is used as a herbal medicine in Asian countries. Its flowers have been used in folk medicine in the clinic and in making food or healthy beverages for over 1500years in China. To investigate the molecular processes involved in L. japonica development from buds to flowers exposed to UV radiation, a comparative proteomics analysis was performed. Fifty-four proteins were identified as differentially expressed, including 42 that had increased expression and 12 that had decreased expression. The levels of the proteins related to glycolysis, TCA/organic acid transformation, major carbohydrate metabolism, oxidative pentose phosphate, stress, secondary metabolism, hormone, and mitochondrial electron transport were increased during flower opening process after exposure to UV radiation. Six metabolites in L. japonica buds and flowers were identified and relatively quantified using LC-MS/MS. The antioxidant activity was performed using a 1,1-diphenyl-2-picrylhydrazyl assay, which revealed that L. japonica buds had more activity than the UV irradiated flowers. This suggests that UV-B radiation induces production of endogenous ethylene in L. japonica buds, thus facilitating blossoming of the buds and activating the antioxidant system. Additionally, the higher metabolite contents and antioxidant properties of L. japonica buds indicate that the L. japonica bud stage may be a more optimal time to harvest than the flower stage when using for medicinal properties.
    Matched MeSH terms: Citric Acid Cycle/radiation effects
  3. Wong YC, Teh HF, Mebus K, Ooi TEK, Kwong QB, Koo KL, et al.
    BMC Genomics, 2017 06 21;18(1):470.
    PMID: 28637447 DOI: 10.1186/s12864-017-3855-7
    BACKGROUND: The oil yield trait of oil palm is expected to involve multiple genes, environmental influences and interactions. Many of the underlying mechanisms that contribute to oil yield are still poorly understood. In this study, we used a microarray approach to study the gene expression profiles of mesocarp tissue at different developmental stages, comparing genetically related high- and low- oil yielding palms to identify genes that contributed to the higher oil-yielding palm and might contribute to the wider genetic improvement of oil palm breeding populations.

    RESULTS: A total of 3412 (2001 annotated) gene candidates were found to be significantly differentially expressed between high- and low-yielding palms at at least one of the different stages of mesocarp development evaluated. Gene Ontologies (GO) enrichment analysis identified 28 significantly enriched GO terms, including regulation of transcription, fatty acid biosynthesis and metabolic processes. These differentially expressed genes comprise several transcription factors, such as, bHLH, Dof zinc finger proteins and MADS box proteins. Several genes involved in glycolysis, TCA, and fatty acid biosynthesis pathways were also found up-regulated in high-yielding oil palm, among them; pyruvate dehydrogenase E1 component Subunit Beta (PDH), ATP-citrate lyase, β- ketoacyl-ACP synthases I (KAS I), β- ketoacyl-ACP synthases III (KAS III) and ketoacyl-ACP reductase (KAR). Sucrose metabolism-related genes such as Invertase, Sucrose Synthase 2 and Sucrose Phosphatase 2 were found to be down-regulated in high-yielding oil palms, compared to the lower yield palms.

    CONCLUSIONS: Our findings indicate that a higher carbon flux (channeled through down-regulation of the Sucrose Synthase 2 pathway) was being utilized by up-regulated genes involved in glycolysis, TCA and fatty acid biosynthesis leading to enhanced oil production in the high-yielding oil palm. These findings are an important stepping stone to understand the processes that lead to production of high-yielding oil palms and have implications for breeding to maximize oil production.

    Matched MeSH terms: Citric Acid Cycle/genetics
  4. Muhammad SNH, Yaacob NS, Safuwan NAM, Fauzi AN
    PMID: 33906591 DOI: 10.2174/1871520621666210427104804
    BACKGROUND: Survival and progression of cancer cells are highly dependent on aerobic glycolysis. Strobilanthes crispus has been shown to have promising anticancer effects on breast cancer cells. The involvement of the glycolysis pathway in producing these effects is unconfirmed, thus further investigation is required to elucidate this phenomenon.

    OBJECTIVE: This study aims to determine the effect of S. crispus active fraction (F3) and its bioactive components on glycolysis in triple-negative breast cancer cells (MDA-MB-231).

    METHODS: This study utilizes F3, lutein, β-sitosterol, and stigmasterol to be administered in MDA-MB-231 cells for measurement of antiglycolytic activities through cell poliferation, glucose uptake, and lactate concentration assays. Cell proliferation was assessed by MTT assay of MDA-MB-231 cells after treatment with F3 and its bioactive components lutein, β-sitosterol, and stigmasterol. The IC50 value in each compound was determined by MTT assay to be used in subsequent assays. The determination of glucose uptake activity and lactate concentration were quantified using fluorescence spectrophotometry.

    RESULTS: Antiproliferative activities were observed for F3 and its bioactive components, with IC50 values of 100 µg/mL (F3), 20 µM (lutein), 25 µM (β-sitosterol), and 90 μM (stigmasterol) in MDA-MB-231 cells at 48 h. The percentage of glucose uptake and lactate concentration in MDA-MB-231 cells treated with F3, lutein, or β sitosterol were significantly lower than those observed in the untreated cells in a time-dependent manner. However, treatment with stigmasterol decreased the concentration of lactate without affecting the glucose uptake in MDA-MB-231 cells.

    CONCLUSION: The antiglycolytic activities of F3 on MDA-MB-231 cells are attributed to its bioactive components.

    Matched MeSH terms: Citric Acid Cycle
  5. Kamarudin AN, Lai KS, Lamasudin DU, Idris AS, Balia Yusof ZN
    Front Plant Sci, 2017;8:1799.
    PMID: 29089959 DOI: 10.3389/fpls.2017.01799
    Thiamine, or vitamin B1 plays an indispensable role as a cofactor in crucial metabolic reactions including glycolysis, pentose phosphate pathway and the tricarboxylic acid cycle in all living organisms. Thiamine has been shown to play a role in plant adaptation toward biotic and abiotic stresses. The modulation of thiamine biosynthetic genes in oil palm seedlings was evaluated in response to root colonization by endophytic Hendersonia toruloidea. Seven-month-old oil palm seedlings were inoculated with H. toruloidea and microscopic analyses were performed to visualize the localization of endophytic H. toruloidea in oil palm roots. Transmission electron microscopy confirmed that H. toruloidea colonized cortical cells. The expression of thiamine biosynthetic genes and accumulation of total thiamine in oil palm seedlings were also evaluated. Quantitative real-time PCR was performed to measure transcript abundances of four key thiamine biosynthesis genes (THI4, THIC, TH1, and TPK) on days 1, 7, 15, and 30 in response to H. toruloidea colonization. The results showed an increase of up to 12-fold in the expression of all gene transcripts on day 1 post-inoculation. On days 7, 15, and 30 post-inoculation, the relative expression levels of these genes were shown to be downregulated. Thiamine accumulation was observed on day 7 post-colonization and subsequently decreased until day 30. This work provides the first evidence for the enhancement of thiamine biosynthesis by endophytic colonization in oil palm seedlings.
    Matched MeSH terms: Citric Acid Cycle
  6. Ng, Yen, Green Mark, A.
    MyJurnal
    Carbon-11 labeled radiotracers, such as 11C-acetate and
    11C-palmitate are widely used in positron
    emission tomography (PET) for noninvasive evaluation of myocardial metabolism under varied
    physiological conditions.These tracers are attractive probes of tissue physiology, because they are
    simply radiolabled versions of the native biochemical substrates. One of the major metabolites
    generated by these tracers upon the administration is 11CO2 produced via the citric acid cycle. In
    quantitative modeling of
    11C-acetate and
    11C-palmitate PET data, the fraction of blood
    11C
    radioactivity present as
    11CO2 needs to be measured to obtain a correct radiotracer arterial
    input function. Accordingly, the literature describes a method whereby the total blood
    11C-activity
    is counted in blood samples treated with base solution, while the fraction of
    1 1CO2 is measured
    after the blood is treated with acid followed by a 10 minutes gas-purge. However, a detailed
    description of the experimental validation of this method was not provided. The goal of this study
    was to test the reliability of a 10 minute gas purging method used to assay
    11CO2 radioactivity in
    blood
    Matched MeSH terms: Citric Acid Cycle
  7. Lau BYC, Amiruddin MD, Othman A
    Data Brief, 2020 Aug;31:105714.
    PMID: 32462070 DOI: 10.1016/j.dib.2020.105714
    Proteome data was obtained from the fruit mesocarps of the two oil palm species, namely, the African Elaeis guineensis (commercial tenera or commonly known as D x P and MPOB-Nigerian tenera) and the South American Elaeis oleifera. Total proteins were extracted from randomly selected fruitlets and subjected to proteomics characterisation by means of liquid chromatography mass spectrometry. Number of proteins identified, the grouping of the biological replicates from five developmental weeks after anthesis, and the localisation of gene corresponded to the detected proteins on the oil palm chromosomes, were presented. A total of 4,116, 4,210 and 4,081 proteins were found in commercial tenera and MPOB Nigerian tenera for Elaeis guineensis; and Elaeis oleifera, respectively. Principal component analysis showed two distinct clusters that corresponded to Elaeis guineensis and Elaeis oleifera. Collectively, genes that corresponded to the identified proteins were found to be located in all 16 oil palm chromosomes. A total of 59 proteins from Elaeis guineensis and Elaeis oleifera were down-regulated for >5-fold change during the peak of lipid biosynthesis compared to the onset. The same comparative analysis revealed that 66 proteins were up-regulated for >5-fold change. About 60.0% of the observed proteins were involved in catalytic activity while 28.5% were associated with redox reaction. Based on same datasets, the tricarboxylic acid cycle and 5-hydroxytryptamine degradation pathways were found to be enriched the most (>36-fold change). These data can be used to support the oil palm gene model validation and lipid metabolism research, particularly in the areas of oil yield and quality. The tabulated protein lists of identified proteins and their expression changes from these varieties were provided as supplementary files. Raw MSF and mzid files for all the oil palm species were deposited in the ProteomeXchange (PXD017436).
    Matched MeSH terms: Citric Acid Cycle
  8. Kato T, Azegami J, Yokomori A, Dohra H, El Enshasy HA, Park EY
    BMC Genomics, 2020 Apr 23;21(1):319.
    PMID: 32326906 DOI: 10.1186/s12864-020-6709-7
    BACKGROUND: Ashbya gossypii naturally overproduces riboflavin and has been utilized for industrial riboflavin production. To improve riboflavin production, various approaches have been developed. In this study, to investigate the change in metabolism of a riboflavin-overproducing mutant, namely, the W122032 strain (MT strain) that was isolated by disparity mutagenesis, genomic analysis was carried out.

    RESULTS: In the genomic analysis, 33 homozygous and 1377 heterozygous mutations in the coding sequences of the genome of MT strain were detected. Among these heterozygous mutations, the proportion of mutated reads in each gene was different, ranging from 21 to 75%. These results suggest that the MT strain may contain multiple nuclei containing different mutations. We tried to isolate haploid spores from the MT strain to prove its ploidy, but this strain did not sporulate under the conditions tested. Heterozygous mutations detected in genes which are important for sporulation likely contribute to the sporulation deficiency of the MT strain. Homozygous and heterozygous mutations were found in genes encoding enzymes involved in amino acid metabolism, the TCA cycle, purine and pyrimidine nucleotide metabolism and the DNA mismatch repair system. One homozygous mutation in AgILV2 gene encoding acetohydroxyacid synthase, which is also a flavoprotein in mitochondria, was found. Gene ontology (GO) enrichment analysis showed heterozygous mutations in all 22 DNA helicase genes and genes involved in oxidation-reduction process.

    CONCLUSION: This study suggests that oxidative stress and the aging of cells were involved in the riboflavin over-production in A. gossypii riboflavin over-producing mutant and provides new insights into riboflavin production in A. gossypii and the usefulness of disparity mutagenesis for the creation of new types of mutants for metabolic engineering.

    Matched MeSH terms: Citric Acid Cycle/genetics
  9. Lee YV, Wahab HA, Choong YS
    Biomed Res Int, 2015;2015:895453.
    PMID: 25649791 DOI: 10.1155/2015/895453
    Isocitrate lyase (ICL) is the first enzyme involved in glyoxylate cycle. Many plants and microorganisms are relying on glyoxylate cycle enzymes to survive upon downregulation of tricarboxylic acid cycle (TCA cycle), especially Mycobacterium tuberculosis (MTB). In fact, ICL is a potential drug target for MTB in dormancy. With the urge for new antitubercular drug to overcome tuberculosis treat such as multidrug resistant strain and HIV-coinfection, the pace of drug discovery has to be increased. There are many approaches to discovering potential inhibitor for MTB ICL and we hereby review the updated list of them. The potential inhibitors can be either a natural compound or synthetic compound. Moreover, these compounds are not necessary to be discovered only from MTB ICL, as it can also be discovered by a non-MTB ICL. Our review is categorized into four sections, namely, (a) MTB ICL with natural compounds; (b) MTB ICL with synthetic compounds; (c) non-MTB ICL with natural compounds; and (d) non-MTB ICL with synthetic compounds. Each of the approaches is capable of overcoming different challenges of inhibitor discovery. We hope that this paper will benefit the discovery of better inhibitor for ICL.
    Matched MeSH terms: Citric Acid Cycle
  10. Hashim NAA, Ab-Rahim S, Suddin LS, Saman MSA, Mazlan M
    Molecular and clinical oncology, 2019 Jul;11(1):3-14.
    PMID: 31289671 DOI: 10.3892/mco.2019.1853
    Accurate diagnosis of colorectal cancer (CRC) relies on the use of invasive tools such as colonoscopy and sigmoidoscopy. Non-invasive tools are less sensitive in detecting the disease, particularly in the early stage. A number of researchers have used metabolomics analyses on serum/plasma samples of patients with CRC compared with normal healthy individuals in an effort to identify biomarkers for CRC. The aim of the present review is to compare reported serum metabolomics profiles of CRC and to identify common metabolites affected among these studies. A literature search was performed to include any experimental studies on global metabolomics profile of CRC using serum/plasma samples published up to March 2018. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used to assess the quality of the studies reviewed. In total, nine studies were included. The studies used various analytical platforms and were performed on different populations. A pathway enrichment analysis was performed using the data from all the studies under review. The most affected pathways identified were protein biosynthesis, urea cycle, ammonia recycling, alanine metabolism, glutathione metabolism and citric acid cycle. The metabolomics analysis revealed levels of metabolites of glycolysis, tricarboxylic acid cycle, anaerobic respiration, protein, lipid and glutathione metabolism were significantly different between cancer and control samples. Although the majority of differentiating metabolites identified were different in the different studies, there were several metabolites that were common. These metabolites include pyruvic acid, glucose, lactic acid, malic acid, fumaric acid, 3-hydroxybutyric acid, tryptophan, phenylalanine, tyrosine, creatinine and ornithine. The consistent dysregulation of these metabolites among the different studies suggest the possibility of common diagnostic biomarkers for CRC.
    Matched MeSH terms: Citric Acid Cycle
  11. Cheng P, Wang Y, Liang J, Wu Y, Wright A, Liao X
    Front Microbiol, 2018;9:1342.
    PMID: 29988353 DOI: 10.3389/fmicb.2018.01342
    There is growing interest in the use of unconventional feed ingredients containing higher dietary fiber for pig production due to increasing prices of cereal grains and the potential health benefits of dietary fiber on host animals. This study aimed to gain insight into the community-wide microbiome population between the Chinese native Lantang pigs and the commercial Duroc pigs to uncover the microbiological mechanisms for the degradation capacity of fiber in pigs. Utilizing the metagenomics approach, we compared the phylogeny and functional capacity of the fecal microbiome from approximately 150-day-old female Lantang and Duroc pigs fed a similar diet. The structure of the fecal microbial community from the two pig breeds was different at the genus level; the number of genes associated with fiber degradation was higher in Lantang pigs. Further analysis and prediction of their functions from the fecal microbiomes of the two pig breeds revealed that the degradation capacities of fiber, branched chain fatty acids, and oligosaccharides were higher in Lantang pigs. The ability of lignocellulose bonding modules and the transport capacities of xylose, L-arabinose, ribose and methyl galactose were also higher in Lantang pigs. Similarly, the metabolic capacities of xylose, ribose, and fucose and the potential effectiveness of the tricarboxylic acid cycle (TCA) and gene abundance in the hydrogen sink pathway were higher in the fecal microbiome from Lantang pigs. Lantang pigs have a higher capacity to utilize dietary fiber than Duroc pigs, and the differences in the capability to utilize dietary fiber between the indigenous and commercial pigs could be differences in the composition and biological function of the gut microbiota.
    Matched MeSH terms: Citric Acid Cycle
  12. Supandi F, van Beek JHGM
    PLoS One, 2018;13(9):e0203687.
    PMID: 30208076 DOI: 10.1371/journal.pone.0203687
    BACKGROUND: Parkinson's disease is a widespread neurodegenerative disorder which affects brain metabolism. Although changes in gene expression during disease are often measured, it is difficult to predict metabolic fluxes from gene expression data. Here we explore the hypothesis that changes in gene expression for enzymes tend to parallel flux changes in biochemical reaction pathways in the brain metabolic network. This hypothesis is the basis of a computational method to predict metabolic flux changes from post-mortem gene expression measurements in Parkinson's disease (PD) brain.

    RESULTS: We use a network model of central metabolism and optimize the correspondence between relative changes in fluxes and in gene expression. To this end we apply the Least-squares with Equalities and Inequalities algorithm integrated with Flux Balance Analysis (Lsei-FBA). We predict for PD (1) decreases in glycolytic rate and oxygen consumption and an increase in lactate production in brain cortex that correspond with measurements (2) relative flux decreases in ATP synthesis, in the malate-aspartate shuttle and midway in the TCA cycle that are substantially larger than relative changes in glucose uptake in the substantia nigra, dopaminergic neurons and most other brain regions (3) shifts in redox shuttles between cytosol and mitochondria (4) in contrast to Alzheimer's disease: little activation of the gamma-aminobutyric acid shunt pathway in compensation for decreased alpha-ketoglutarate dehydrogenase activity (5) in the globus pallidus internus, metabolic fluxes are increased, reflecting increased functional activity.

    CONCLUSION: Our method predicts metabolic changes from gene expression data that correspond in direction and order of magnitude with presently available experimental observations during Parkinson's disease, indicating that the hypothesis may be useful for some biochemical pathways. Lsei-FBA generates predictions of flux distributions in neurons and small brain regions for which accurate metabolic flux measurements are not yet possible.

    Matched MeSH terms: Citric Acid Cycle
  13. Zhu W, Zhong Z, Liu S, Yang B, Komatsu S, Ge Z, et al.
    Int J Mol Sci, 2019 Jan 16;20(2).
    PMID: 30654535 DOI: 10.3390/ijms20020365
    Morus alba is an important medicinal plant that is used to treat human diseases. The leaf, branch, and root of Morus can be applied as antidiabetic, antioxidant, and anti-inflammatory medicines, respectively. To explore the molecular mechanisms underlying the various pharmacological functions within different parts of Morus, organ-specific proteomics were performed. Protein profiles of the Morus leaf, branch, and root were determined using a gel-free/label-free proteomic technique. In the Morus leaf, branch, and root, a total of 492, 414, and 355 proteins were identified, respectively, including 84 common proteins. In leaf, the main function was related to protein degradation, photosynthesis, and redox ascorbate/glutathione metabolism. In branch, the main function was related to protein synthesis/degradation, stress, and redox ascorbate/glutathione metabolism. In root, the main function was related to protein synthesis/degradation, stress, and cell wall. Additionally, organ-specific metabolites and antioxidant activities were analyzed. These results revealed that flavonoids were highly accumulated in Morus root compared with the branch and leaf. Accordingly, two root-specific proteins named chalcone flavanone isomerase and flavonoid 3,5-hydroxylase were accumulated in the flavonoid pathway. Consistent with this finding, the content of the total flavonoids was higher in root compared to those detected in branch and leaf. These results suggest that the flavonoids in Morus root might be responsible for its biological activity and the root is the main part for flavonoid biosynthesis in Morus.
    Matched MeSH terms: Citric Acid Cycle
  14. Ravera S, Ferrando S, Agas D, De Angelis N, Raffetto M, Sabbieti MG, et al.
    J Biophotonics, 2019 09;12(9):e201900101.
    PMID: 31033186 DOI: 10.1002/jbio.201900101
    Photobiomodulation (PBM) is a non-plant-cell manipulation through a transfer of energy by means of light sources at the non-ablative or thermal intensity. Authors showed that cytochrome-c-oxidase (complex IV) is the specific chromophore's target of PBM at the red (600-700 nm) and NIR (760-900 nm) wavelength regions. Recently, it was suggested that the infrared region of the spectrum could influence other chromospheres, despite the interaction by wavelengths higher than 900 nm with mitochondrial chromophores was not clearly demonstrated. We characterized the interaction between mitochondria respiratory chain, malate dehydrogenase, a key enzyme of Krebs cycle, and 3-hydroxyacyl-CoA dehydrogenase, an enzyme involved in the β-oxidation (two mitochondrial matrix enzymes) with the 1064 nm Nd:YAG (100mps and 10 Hz frequency mode) irradiated at the average power density of 0.50, 0.75, 1.00, 1.25 and 1.50 W/cm2 to generate the respective fluences of 30, 45, 60, 75 and 90 J/cm2 . Our results show the effect of laser light on the transmembrane mitochondrial complexes I, III, IV and V (adenosine triphosphate synthase) (window effects), but not on the extrinsic mitochondrial membrane complex II and mitochondria matrix enzymes. The effect is not due to macroscopical thermal change. An interaction of this wavelength with the Fe-S proteins and Cu-centers of respiratory complexes and with the water molecules could be supposed.
    Matched MeSH terms: Citric Acid Cycle
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