scholarly journals Inhibitory Effects of Diketopiperazines from Marine-Derived Streptomyces puniceus on the Isocitrate Lyase of Candida albicans

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2111 ◽  
Author(s):  
Heegyu Kim ◽  
Ji-Yeon Hwang ◽  
Jongheon Shin ◽  
Ki-Bong Oh
Keyword(s):  
Candida Albicans ◽  
Cyclic Peptides ◽  
Inhibitory Concentration ◽  
Isocitrate Lyase ◽  
Glyoxylate Cycle ◽  
Malate Synthase ◽  
Wild Type ◽  
Inhibitory Effects ◽  
Reported Data ◽  
The Glyoxylate Cycle

The glyoxylate cycle is a sequence of anaplerotic reactions catalyzed by the key enzymes isocitrate lyase (ICL) and malate synthase, and plays an important role in the pathogenesis of microorganisms during infection. An icl-deletion mutant of Candida albicans exhibited reduced virulence in mice compared with the wild type. Five diketopiperazines, which are small and stable cyclic peptides, isolated from the marine-derived Streptomyces puniceus Act1085, were evaluated for their inhibitory effects on C. albicans ICL. The structures of these compounds were elucidated based on spectroscopic data and comparisons with previously reported data. Cyclo(L-Phe-L-Val) was identified as a potent ICL inhibitor, with a half maximal inhibitory concentration of 27 μg/mL. Based on the growth phenotype of the icl-deletion mutants and icl expression analyses, we demonstrated that cyclo(L-Phe-L-Val) inhibits the gene transcription of ICL in C. albicans under C2-carbon-utilizing conditions.

scholarly journals Inhibitory Effects of Epipolythiodioxopiperazine Fungal Metabolites on Isocitrate Lyase in the Glyoxylate Cycle of Candida albicans

Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 295
Author(s):  
Ji-Yeon Hwang ◽  
Beomkoo Chung ◽  
Oh-Seok Kwon ◽  
Sung Chul Park ◽  
Eunji Cho ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Inhibitory Concentration ◽  
Isocitrate Lyase ◽  
Glyoxylate Cycle ◽  
Spectroscopic Techniques ◽  
Fungal Metabolites ◽  
Inhibitory Effects ◽  
Polymerase Chain ◽  
Reported Data ◽  
The Glyoxylate Cycle

Four epipolythiodioxopiperazine fungal metabolites (1–4) isolated from the sponge-derived Aspergillus quadrilineatus FJJ093 were evaluated for their capacity to inhibit isocitrate lyase (ICL) in the glyoxylate cycle of Candida albicans. The structures of these compounds were elucidated using spectroscopic techniques and comparisons with previously reported data. We found secoemestrin C (1) (an epitetrathiodioxopiperazine derivative) to be a potent ICL inhibitor, with an inhibitory concentration of 4.77 ± 0.08 μM. Phenotypic analyses of ICL-deletion mutants via growth assays with acetate as the sole carbon source demonstrated that secoemestrin C (1) inhibited C. albicans ICL. Semi-quantitative reverse-transcription polymerase chain reaction analyses indicated that secoemestrin C (1) inhibits ICL mRNA expression in C. albicans under C2-assimilating conditions.

Co-ordinate regulation of genes involved in storage lipid mobilization in Arabidopsis thaliana

2001 ◽  
Vol 29 (2) ◽  
pp. 283-286 ◽  
Author(s):  
E. L. Rylott ◽  
M. A. Hooks ◽  
I. A. Graham
Keyword(s):  
Arabidopsis Thaliana ◽  
Enzyme Activities ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Isocitrate Lyase ◽  
Glyoxylate Cycle ◽  
Molecular Genetic ◽  
Regulation Of Gene Expression ◽  
Growth Period ◽  
Malate Synthase ◽  
The Glyoxylate Cycle

Molecular genetic approaches in the model plant Arabidopsis thaliana (ColO) are shedding new light on the role and control of the pathways associated with the mobilization of lipid reserves during oilseed germination and post-germinative growth. Numerous independent studies have reported on the expression of individual genes encoding enzymes from the three major pathways: β-oxidation, the glyoxylate cycle and gluconeogenesis. However, a single comprehensive study of representative genes and enzymes from the different pathways in a single plant species has not been done. Here we present results from Arabidopsis that demonstrate the co-ordinate regulation of gene expression and enzyme activities for the acyl-CoA oxidase- and 3-ketoacyl-CoA thiolasemediated steps of β-oxidation, the isocitrate lyase and malate synthase steps of the glyoxylate cycle and the phosphoenolpyruvate carboxykinase step of gluconeogenesis. The mRNA abundance and enzyme activities increase to a peak at stage 2, 48 h after the onset of seed germination, and decline thereafter either to undetectable levels (for malate synthase and isocitrate lyase) or low basal levels (for the genes of β-oxidation and gluconeogenesis). The co-ordinate induction of all these genes at the onset of germination raises the possibility that a global regulatory mechanism operates to induce the expression of genes associated with the mobilization of storage reserves during the heterotrophic growth period.

Acetate metabolism in Escherichia coli

1978 ◽  
Vol 24 (2) ◽  
pp. 149-153 ◽  
Author(s):  
T. M. Lakshmi ◽  
Robert B. Helling
Keyword(s):  
Isocitrate Dehydrogenase ◽  
Citrate Synthase ◽  
Isocitrate Lyase ◽  
Glyoxylate Cycle ◽  
Acetate Metabolism ◽  
Wild Type ◽  
Intermediary Metabolites ◽  
Lyase Activity ◽  
Acetate Medium ◽  
The Glyoxylate Cycle

Levels of several intermediary metabolites were measured in cells grown in acetate medium in order to test the hypothesis that the glyoxylate cycle is repressed by phosphoenolpyruvate (PEP). Wild-type cells had less PEP than either isocitrate dehydrogenase – deficient cells (which had greater isocitrate lyase activity than the wild type) or isocitrate dehydrogenase – deficient, citrate synthase – deficient cells (which are poorly inducible). Thus induction of the glyoxylate cycle is more complicated than a simple function of PEP concentration. No correlation between enzyme activity and the level of oxaloacetate, pyruvate, or citrate was found either. Citrate was synthesized in citrate synthase – deficient mutants, possibly via citrate lyase.

STUDIES ON RUMEN COLIFORM ORGANISMS: II. UTILIZATION OF ACETATE BY ESCHERICHIA COLI 64 ISOLATED FROM THE RUMEN FLUID OF A COW FED ALFALFA HAY

1967 ◽  
Vol 47 (3) ◽  
pp. 199-209 ◽  
Author(s):  
C. R. Krishnamurti ◽  
L. W. McElroy
Keyword(s):  
Sodium Acetate ◽  
Isocitrate Lyase ◽  
Protein Hydrolysate ◽  
Rumen Fluid ◽  
Glyoxylate Cycle ◽  
Malate Synthase ◽  
E Coli ◽  
Spectrophotometric Methods ◽  
Acetate Medium ◽  
The Glyoxylate Cycle

When cells of E. coli 64 were harvested in their exponential phase of growth in an acetate medium and incubated aerobically with sodium acetate-2-C14, about 33% of the label appeared in CO2 after 1 hr. Of the radioactivity in the cells, 72% was recovered in the protein hydrolysate, 8% in the nucleic acid, 6% in the lipid and 14% in the ethanol-soluble fractions. The radioactivity in the protein hydrolysate of cells incubated with sodium acetate-2-C14 was approximately 20 times that in the hydrolysate of cells incubated with C14O2 as the carbon source. By spectrophotometric methods, it was demonstrated that cell-free extracts of cells grown on acetate contained acetate kinase and phosphate acetyltransferase, plus, as demonstrated by spectrophotometric and isotopic methods, isocitrate lyase and malate synthase which are characteristic of the glyoxylate cycle. The enzymes of the glyoxylate cycle could not be demonstrated in cell-free extracts of E. coli 64 grown on glucose under either aerobic or anaerobic conditions. Possible functions that E. coli 64 may have in the maintenance of anaerobiosis in the rumen and utilization of acetate through the glyoxylate pathway are discussed.

Changes in metabolic reserves and enzyme activities during zoospore motility and cyst germination in Phytophthora palmivora

1975 ◽  
Vol 53 (14) ◽  
pp. 1411-1416 ◽  
Author(s):  
Christina E. Bimpong
Keyword(s):  
Specific Activity ◽  
Isocitrate Lyase ◽  
Glyoxylate Cycle ◽  
Krebs Cycle ◽  
Malate Synthase ◽  
Phytophthora Palmivora ◽  
Germination Period ◽  
Major Energy Source ◽  
The Glyoxylate Cycle ◽  
Cyst Germination

Lipids measured as acyl glycerides and free fatty acids provided the major energy source during a 6-h motile and a 2-h germination period in zoospores and cysts, respectively, of Phytophthora palmivora. Carbohydrates and proteins decreased slightly during the 6-h motile period but increased significantly during germination. Specific activity of isocitrate lyase decreased both during zoospore motility and cyst germination. Only trace amounts of malate synthase activity were detected in zoospores and cysts. The activities of both NAD-isocitrate and malate dehydrogenases increased slightly, while those of NADP-isocitrate and succinate dehydrogenases decreased during the 6-h motile period. During the 2-h germination period the specific activities of NAD- and NADP-isocitrate, malate, and succinate dehydrogenases increased. It appears that during the motile stage the glyoxylate cycle provided more metabolites for the Krebs cycle than it did during germination.

scholarly journals Delicate Metabolic Control and Coordinated Stress Response Critically Determine Antifungal Tolerance of Candida albicans Biofilm Persisters

2015 ◽  
Vol 59 (10) ◽  
pp. 6101-6112 ◽  
Author(s):  
Peng Li ◽  
Chaminda J. Seneviratne ◽  
Emanuele Alpi ◽  
Juan A. Vizcaino ◽  
Lijian Jin
Keyword(s):  
Candida Albicans ◽  
Stress Response ◽  
Metabolic Control ◽  
Isocitrate Lyase ◽  
Tricarboxylic Acid Cycle ◽  
Glyoxylate Cycle ◽  
Malate Synthase ◽  
Content Type ◽  
Liquid Chromatography Tandem Mass ◽  
Metabolic Activities

ABSTRACTCandidainfection has emerged as a critical health care burden worldwide, owing to the formation of robust biofilms against common antifungals. Recent evidence shows that multidrug-tolerant persisters critically account for biofilm recalcitrance, but their underlying biological mechanisms are poorly understood. Here, we first investigated the phenotypic characteristics ofCandidabiofilm persisters under consecutive harsh treatments of amphotericin B. The prolonged treatments effectively killed the majority of the cells of biofilms derived from representative strains ofCandida albicans,Candida glabrata, andCandida tropicalisbut failed to eradicate a small fraction of persisters. Next, we explored the tolerance mechanisms of the persisters through an investigation of the proteomic profiles ofC. albicansbiofilm persister fractions by liquid chromatography-tandem mass spectrometry. TheC. albicansbiofilm persisters displayed a specific proteomic signature, with an array of 205 differentially expressed proteins. The crucial enzymes involved in glycolysis, the tricarboxylic acid cycle, and protein synthesis were markedly downregulated, indicating that major metabolic activities are subdued in the persisters. It is noteworthy that certain metabolic pathways, such as the glyoxylate cycle, were able to be activated with significantly increased levels of isocitrate lyase and malate synthase. Moreover, a number of important proteins responsible forCandidagrowth, virulence, and the stress response were greatly upregulated. Interestingly, the persisters were tolerant to oxidative stress, despite highly induced intracellular superoxide. The current findings suggest that delicate metabolic control and a coordinated stress response may play a crucial role in mediating the survival and antifungal tolerance ofCandidabiofilm persisters.

scholarly journals The Glyoxylate Cycle Is Involved in White-Opaque Switching in Candida albicans

2021 ◽  
Vol 7 (7) ◽  
pp. 502
Author(s):  
Susana Hidalgo Vico ◽  
Daniel Prieto ◽  
Rebeca Alonso Monge ◽  
Elvira Román ◽  
Jesús Pla
Keyword(s):  
Transcription Factor ◽  
Candida Albicans ◽  
Gastrointestinal Tract ◽  
Isocitrate Lyase ◽  
Glyoxylate Cycle ◽  
Carbon Sources ◽  
Glyoxylate Shunt ◽  
Phenotypic Analysis ◽  
Altered Metabolism ◽  
The Glyoxylate Cycle

Candida albicans is a commensal yeast that inhabits the gastrointestinal tract of humans. The master regulator of the white-opaque transition WOR1 has been implicated in the adaptation to this commensal status. A proteomic analysis of cells overexpressing this transcription factor (WOR1OE) suggested an altered metabolism of carbon sources and a phenotypic analysis confirmed this alteration. The WOR1OE cells are deficient in using trehalose and xylose and are unable to use 2C sources, which is consistent with a reduction in the amount of Icl1, the isocitrate lyase enzyme. The icl1Δ/Δ mutants overexpressing WOR1 are deficient in the production of phloxine B positive cells, a main characteristic of opaque cells, a phenotype also observed in mating type hemizygous mtla1Δ icl1Δ/Δ cells, suggesting the involvement of Icl1 in the adaptation to the commensal state. In fact, icl1Δ/Δ cells have reduced fitness in mouse gastrointestinal tract as compared with essentially isogenic heterozygous ICL1/icl1Δ, but overproduction of WOR1 in an icl1Δ/Δ mutant does not restore fitness. These results implicate the glyoxylate shunt in the adaptation to commensalism of C. albicans by mechanisms that are partially independent of WOR1.

Effect of Leaf Senescence on Glyoxylate Cycle Enzyme Activities

1992 ◽  
Vol 19 (6) ◽  
pp. 723 ◽  
Author(s):  
L Pistelli ◽  
P Perata ◽  
A Alpi
Keyword(s):  
Malate Dehydrogenase ◽  
Enzyme Activities ◽  
Citrate Synthase ◽  
Isocitrate Lyase ◽  
Glyoxylate Cycle ◽  
Malate Synthase ◽  
Cycle Enzyme ◽  
Hydroxypyruvate Reductase ◽  
Foliar Senescence ◽  
The Glyoxylate Cycle

In order to elucidate the metabolism of the peroxisomes during foliar senescence of leaf beet (Beta vulgaris L., var. cicla), peroxisomal activities have been determined at various stages of senescence. Catalase and hydroxypyruvate reductase activities decreased whereas those of the β-oxidation pathway and glyoxylate cycle enzymes increased at the same time. The increased activities of malate synthase, isocitrate lyase, malate dehydrogenase and citrate synthase indicate that the glyoxylate cycle might be activated during the foliar senescence of leaf beet.

scholarly journals The localization of enzymes of intermediary metabolism in Astasia and Euglena

1973 ◽  
Vol 134 (2) ◽  
pp. 607-616 ◽  
Author(s):  
Nicole Bégin-Heick
Keyword(s):  
Succinate Dehydrogenase ◽  
Isocitrate Lyase ◽  
Tricarboxylic Acid Cycle ◽  
Glyoxylate Cycle ◽  
Intracellular Localization ◽  
Tricarboxylic Acid ◽  
Malate Synthase ◽  
Particulate Fraction ◽  
Acid Cycle ◽  
The Glyoxylate Cycle

Results are presented on the intracellular localization of some of the enzymes of gluconeogenesis, of the tricarboxylic acid cycle and of related enzymes in Astasia and Euglena grown with various substrates. The results indicate the particulate nature of at least part of the malate synthase of Astasia and of part of the malate synthase and isocitrate lyase in Euglena. However, the presence of glyoxysomes (microbodies) in Astasia and Euglena is still open to question, since it has not, so far, been possible to separate the enzymes of the glyoxylate cycle from succinate dehydrogenase in the particulate fraction.

scholarly journals Anaerobic Induction of Isocitrate Lyase and Malate Synthase in Submerged Rice Seedlings Indicates the Important Metabolic Role of the Glyoxylate Cycle

2005 ◽  
Vol 37 (6) ◽  
pp. 406-414 ◽  
Author(s):  
Ying Lu ◽  
Yong-Rui Wu ◽  
Bin Han
Keyword(s):  
Isocitrate Lyase ◽  
Tricarboxylic Acid Cycle ◽  
Glyoxylate Cycle ◽  
Fold Increase ◽  
Malate Synthase ◽  
Acetate Metabolism ◽  
Activity Assay ◽  
Rice Seedlings ◽  
Metabolic Role ◽  
The Glyoxylate Cycle

Abstract The glyoxylate cycle is a modified form of the tricarboxylic acid cycle that converts C2 compounds into C4 dicarboxylic acids at plant developmental stages. By studying submerged rice seedlings, we revealed the activation of the glyoxylate cycle by identifying the increased transcripts of mRNAs of the genes of isocitrate lyase (ICL) and malate synthase (MS), two characteristic enzymes of the glyoxylate cycle. Northern blot analysis showed that ICL and MS were activated in the prolonged anaerobic environment. The activity assay of pyruvate decarboxylase and ICL in the submerged seedlings indicated an 8.8-fold and 3.5-fold increase over that in the unsubmerged seedlings, respectively. The activity assay of acetyl-coenzyme A synthetase in the submerged seedlings indicated a 3-fold increase over that in the unsubmerged seedlings, which is important for initiating acetate metabolism. Consequently, we concluded that the glyoxylate cycle was involved in acetate metabolism under anaerobic conditions.

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