Lipid metabolism inGiardia: a post-genomic perspective

SUMMARYGiardia lamblia, a protozoan parasite, infects a wide variety of vertebrates, including humans. Studies indicate that this anaerobic protist possesses a limited ability to synthesize lipid moleculesde novoand depends on supplies from its environment for growth and differentiation. It has been suggested that most lipids and fatty acids are taken up by endocytic and non-endocytic pathways and are used byGiardiafor energy production and membrane/organelle biosynthesis. The purpose of this article is to provide an update on recent progress in the field of lipid research of this parasite and the validation of lipid metabolic pathways through recent genomic information. Based on current cellular, biochemical and genomic data, a comprehensive pathway has been proposed to facilitate our understanding of lipid and fatty acid metabolism/syntheses in this waterborne pathogen. We envision that the current review will be helpful in identifying targets from the pathways that could be used to design novel therapies to control giardiasis and related diseases.

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The Serum Metabolome of Moderate and Severe COVID-19 Patients Reflects Possible Liver Alterations Involving Carbon and Nitrogen Metabolism

International Journal of Molecular Sciences ◽

10.3390/ijms22179548 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9548

Author(s):

Marianna Caterino ◽

Michele Costanzo ◽

Roberta Fedele ◽

Armando Cevenini ◽

Monica Gelzo ◽

...

Keyword(s):

Metabolic Pathways ◽

Energy Production ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Serum Levels ◽

Systemic Effects ◽

Metabolomic Analysis ◽

Carbon And Nitrogen ◽

Carbon And Nitrogen Metabolism ◽

Global Threat

COVID-19 is a global threat that has spread since the end of 2019, causing severe clinical sequelae and deaths, in the context of a world pandemic. The infection of the highly pathogenetic and infectious SARS-CoV-2 coronavirus has been proven to exert systemic effects impacting the metabolism. Yet, the metabolic pathways involved in the pathophysiology and progression of COVID-19 are still unclear. Here, we present the results of a mass spectrometry-based targeted metabolomic analysis on a cohort of 52 hospitalized COVID-19 patients, classified according to disease severity as mild, moderate, and severe. Our analysis defines a clear signature of COVID-19 that includes increased serum levels of lactic acid in all the forms of the disease. Pathway analysis revealed dysregulation of energy production and amino acid metabolism. Globally, the variations found in the serum metabolome of COVID-19 patients may reflect a more complex systemic perturbation induced by SARS-CoV-2, possibly affecting carbon and nitrogen liver metabolism.

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Metabolomic Signature Discriminates Normal Human Cornea from Keratoconus—A Pilot GC/MS Study

Molecules ◽

10.3390/molecules25122933 ◽

2020 ◽

Vol 25 (12) ◽

pp. 2933

Author(s):

Anna Wojakowska ◽

Monika Pietrowska ◽

Piotr Widlak ◽

Dariusz Dobrowolski ◽

Edward Wylęgała ◽

...

Keyword(s):

Metabolic Pathways ◽

Energy Production ◽

Acid Metabolism ◽

Pathological Condition ◽

Hierarchical Cluster ◽

Unsupervised Hierarchical Cluster ◽

Human Cornea ◽

Cellular Processes ◽

Normal Human ◽

Molecular Etiology

The molecular etiology of keratoconus (KC), a pathological condition of the human cornea, remains unclear. The aim of this work was to perform profiling of metabolites and identification of features discriminating this pathology from the normal cornea. The combination of gas chromatography and mass spectrometry (GC/MS) techniques has been applied for profiling and identification of metabolites in corneal buttons from 6 healthy controls and 7 KC patients. An untargeted GC/MS-based approach allowed the detection of 377 compounds, including 46 identified unique metabolites, whose levels enabled the separation of compared groups of samples in unsupervised hierarchical cluster analysis. There were 13 identified metabolites whose levels differentiated between groups of samples. Downregulation of several carboxylic acids, fatty acids, and steroids was observed in KC when compared to the normal cornea. Metabolic pathways associated with compounds that discriminated both groups were involved in energy production, lipid metabolism, and amino acid metabolism. An observed signature may reflect cellular processes involved in the development of KC pathology, including oxidative stress and inflammation.

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Phytochemicals Block Glucose Utilization and Lipid Synthesis to Counteract Metabolic Reprogramming in Cancer Cells

Applied Sciences ◽

10.3390/app11031259 ◽

2021 ◽

Vol 11 (3) ◽

pp. 1259

Author(s):

Qiong Wu ◽

Bo Zhao ◽

Guangchao Sui ◽

Jinming Shi

Keyword(s):

Cancer Cells ◽

Metabolic Pathways ◽

De Novo ◽

Aerobic Glycolysis ◽

Structural Characteristics ◽

Natural Compounds ◽

Metabolic Reprogramming ◽

De Novo Lipogenesis ◽

Anticancer Activities ◽

Substrate Analogs

Aberrant metabolism is one of the hallmarks of cancers. The contributions of dysregulated metabolism to cancer development, such as tumor cell survival, metastasis and drug resistance, have been extensively characterized. “Reprogrammed” metabolic pathways in cancer cells are mainly represented by excessive glucose consumption and hyperactive de novo lipogenesis. Natural compounds with anticancer activities are constantly being demonstrated to target metabolic processes, such as glucose transport, aerobic glycolysis, fatty acid synthesis and desaturation. However, their molecular targets and underlying anticancer mechanisms remain largely unclear or controversial. Mounting evidence indicated that these natural compounds could modulate the expression of key regulatory enzymes in various metabolic pathways at transcriptional and translational levels. Meanwhile, natural compounds could also inhibit the activities of these enzymes by acting as substrate analogs or altering their protein conformations. The actions of natural compounds in the crosstalk between metabolism modulation and cancer cell destiny have become increasingly attractive. In this review, we summarize the activities of natural small molecules in inhibiting key enzymes of metabolic pathways. We illustrate the structural characteristics of these compounds at the molecular level as either inhibitor of various enzymes or regulators of metabolic pathways in cancer cells. Our ultimate goal is to both facilitate the clinical application of natural compounds in cancer therapies and promote the development of novel anticancer therapeutics.

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Comprehensive transcriptome and metabolome profiling reveal metabolic mechanisms of Nitraria sibirica Pall. to salt stress

Scientific Reports ◽

10.1038/s41598-021-92317-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Huanyong Li ◽

Xiaoqian Tang ◽

Xiuyan Yang ◽

Huaxin Zhang

Keyword(s):

Salt Stress ◽

Amino Acid ◽

Salt Tolerance ◽

Metabolic Pathways ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Sulfur Metabolism ◽

Enrichment Analysis ◽

Extracellular Region ◽

Nitraria Sibirica

AbstractNitraria sibirica Pall., a typical halophyte that can survive under extreme drought conditions and in saline-alkali environments, exhibits strong salt tolerance and environmental adaptability. Understanding the mechanism of molecular and physiological metabolic response to salt stress of plant will better promote the cultivation and use of halophytes. To explore the mechanism of molecular and physiological metabolic of N. sibirica response to salt stress, two-month-old seedlings were treated with 0, 100, and 400 mM NaCl. The results showed that the differentially expressed genes between 100 and 400 mmol L−1 NaCl and unsalted treatment showed significant enrichment in GO terms such as binding, cell wall, extemal encapsulating structure, extracellular region and nucleotide binding. KEGG enrichment analysis found that NaCl treatment had a significant effect on the metabolic pathways in N. sibirica leaves, which mainly including plant-pathogen interaction, amino acid metabolism of the beta alanine, arginine, proline and glycine metabolism, carbon metabolism of glycolysis, gluconeogenesis, galactose, starch and sucrose metabolism, plant hormone signal transduction and spliceosome. Metabolomics analysis found that the differential metabolites between the unsalted treatment and the NaCl treatment are mainly amino acids (proline, aspartic acid, methionine, etc.), organic acids (oxaloacetic acid, fumaric acid, nicotinic acid, etc.) and polyhydric alcohols (inositol, ribitol, etc.), etc. KEGG annotation and enrichment analysis showed that 100 mmol L−1 NaCl treatment had a greater effect on the sulfur metabolism, cysteine and methionine metabolism in N. sibirica leaves, while various amino acid metabolism, TCA cycle, photosynthetic carbon fixation and sulfur metabolism and other metabolic pathways have been significantly affected by 400 mmol L−1 NaCl treatment. Correlation analysis of differential genes in transcriptome and differential metabolites in metabolome have found that the genes of AMY2, BAM1, GPAT3, ASP1, CML38 and RPL4 and the metabolites of L-cysteine, proline, 4-aminobutyric acid and oxaloacetate played an important role in N. sibirica salt tolerance control. This is a further improvement of the salt tolerance mechanism of N. sibirica, and it will provide a theoretical basis and technical support for treatment of saline-alkali soil and the cultivation of halophytes.

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Effects upon metabolic pathways and energy production by Sb(III) and As(III)/Sb(III)-oxidase gene aioA in Agrobacterium tumefaciens GW4

PLoS ONE ◽

10.1371/journal.pone.0172823 ◽

2017 ◽

Vol 12 (2) ◽

pp. e0172823 ◽

Cited By ~ 5

Author(s):

Jingxin Li ◽

Birong Yang ◽

Manman Shi ◽

Kai Yuan ◽

Wei Guo ◽

...

Keyword(s):

Agrobacterium Tumefaciens ◽

Metabolic Pathways ◽

Energy Production ◽

Oxidase Gene

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Metabolism-driven post-translational modifications of H3K9 in early bovine embryos

Reproduction ◽

10.1530/rep-21-0134 ◽

2021 ◽

Vol 162 (3) ◽

pp. 181-191

Author(s):

Jessica Ispada ◽

Aldcejam Martins da Fonseca Junior ◽

Otávio Luiz Ramos Santos ◽

Camila Bruna de Lima ◽

Erika Cristina dos Santos ◽

...

Keyword(s):

Metabolic Pathways ◽

Developmental Stages ◽

De Novo ◽

Blastocyst Stage ◽

Developmental Model ◽

Bovine Embryos ◽

Acetyl Coa ◽

Post Translational Modifications ◽

The Relationship ◽

Different Levels

Metabolic and molecular profiles were reported as different for bovine embryos with distinct kinetics during the first cleavages. In this study, we used this same developmental model (fast vs slow) to determine if the relationship between metabolism and developmental kinetics affects the levels of acetylation or tri-methylation at histone H3 lysine 9 (H3K9ac and H3K9me3, respectively). Fast and slow developing embryos presented different levels of H3K9ac and H3K9me3 from the earliest stages of development (40 and 96 hpi) and up to the blastocyst stage. For H3K9me3, both groups of embryos presented a wave of demethylation and de novo methylation, although it was more pronounced in fast than slow embryos, resulting in blastocysts with higher levels of this mark. The H3K9ac reprogramming profile was distinct between kinetics groups. While slow embryos presented a wave of deacetylation, followed by an increase in this mark at the blastocyst stage, fast embryos reduced this mark throughout all the developmental stages studied. H3K9me3 differences corresponded to writer and eraser transcript levels, while H3K9ac patterns were explained by metabolism-related gene expression. To verify if metabolic differences could alter levels of H3K9ac, embryos were cultured with sodium-iodoacetate (IA) or dichloroacetate (DCA) to disrupt the glycolytic pathway or increase acetyl-CoA production, respectively. IA reduced H3K9ac while DCA increased H3K9ac in blastocysts. Concluding, H3K9me3 and H3K9ac patterns differ between embryos with different kinetics, the second one explained by metabolic pathways involved in acetyl-CoA production. So far, this is the first study demonstrating a relationship between metabolic differences and histone post-translational modifications in bovine embryos.

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Redox, amino acid, and fatty acid metabolism intersect with bacterial virulence in the gut

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1813451115 ◽

2018 ◽

Vol 115 (45) ◽

pp. E10712-E10719 ◽

Cited By ~ 12

Author(s):

Reed Pifer ◽

Regan M. Russell ◽

Aman Kumar ◽

Meredith M. Curtis ◽

Vanessa Sperandio

Keyword(s):

Fatty Acid ◽

High Throughput ◽

Fatty Acid Metabolism ◽

Metabolic Pathways ◽

Virulence Genes ◽

Acid Metabolism ◽

Feedback Mechanism ◽

Regulatory Pathways ◽

Successful Infection ◽

Cellular Circuits

The gut metabolic landscape is complex and is influenced by the microbiota, host physiology, and enteric pathogens. Pathogens have to exquisitely monitor the biogeography of the gastrointestinal tract to find a suitable niche for colonization. To dissect the important metabolic pathways that influence virulence of enterohemorrhagicEscherichia coli(EHEC), we conducted a high-throughput screen. We generated a dataset of regulatory pathways that control EHEC virulence expression under anaerobic conditions. This unraveled that the cysteine-responsive regulator, CutR, converges with the YhaO serine import pump and the fatty acid metabolism regulator FadR to optimally control virulence expression in EHEC. CutR activates expression of YhaO to increase activity of the YhaJ transcription factor that has been previously shown to directly activate the EHEC virulence genes. CutR enhances FadL, which is a pump for fatty acids that represses inhibition of virulence expression by FadR, unmasking a feedback mechanism responsive to metabolite fluctuations. Moreover, CutR and FadR also augment murine infection byCitrobacter rodentium, which is a murine pathogen extensively employed as a surrogate animal model for EHEC. This high-throughput approach proved to be a powerful tool to map the web of cellular circuits that allows an enteric pathogen to monitor the gut environment and adjust the levels of expression of its virulence repertoire toward successful infection of the host.

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The Diverse Functions of Non-Essential Amino Acids in Cancer

Cancers ◽

10.3390/cancers11050675 ◽

2019 ◽

Vol 11 (5) ◽

pp. 675 ◽

Cited By ~ 25

Author(s):

Bo-Hyun Choi ◽

Jonathan L. Coloff

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Cancer Therapy ◽

Metabolic Pathways ◽

Essential Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Essential Amino Acids ◽

Redox Status ◽

Antioxidant Systems

Far beyond simply being 11 of the 20 amino acids needed for protein synthesis, non-essential amino acids play numerous important roles in tumor metabolism. These diverse functions include providing precursors for the biosynthesis of macromolecules, controlling redox status and antioxidant systems, and serving as substrates for post-translational and epigenetic modifications. This functional diversity has sparked great interest in targeting non-essential amino acid metabolism for cancer therapy and has motivated the development of several therapies that are either already used in the clinic or are currently in clinical trials. In this review, we will discuss the important roles that each of the 11 non-essential amino acids play in cancer, how their metabolic pathways are linked, and how researchers are working to overcome the unique challenges of targeting non-essential amino acid metabolism for cancer therapy.

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Metabolic Profiling Revealed Dysregulated Arachidonic Acid Metabolism and Tryptophan Metabolism in the Lungs from Canines with Pacing-induced Heart Failure

10.21203/rs.3.rs-96585/v1 ◽

2020 ◽

Author(s):

Junhan Zhao ◽

Jing Wang ◽

Shengwen Yang ◽

Ran Jing ◽

Xi Liu ◽

...

Keyword(s):

Heart Failure ◽

Arachidonic Acid ◽

Metabolic Pathways ◽

Sham Group ◽

Acid Metabolism ◽

Congestion Management ◽

Arachidonic Acid Metabolism ◽

Tryptophan Metabolism ◽

Negative Ion ◽

Metabolic Signatures

Abstract Background: Lung has critical pathophysiological connections to heart and lung congestion presents one of the hallmark features of heart failure (HF). This study aimed to explore the metabolic signatures and disturbances in lungs under HF condition and provide insights on the pathophysiology of the lungs under HF condition from the perspective of metabolism.Methods: In this study, we established a rapid pacing induced HF canine model and applied a comprehensive untargeted metabolomics method to comparatively assessed the metabolomics profiles in the lung tissues from HF group and sham group. Results: Distinct metabolic signatures were identified in the lungs between beagles in HF group and sham group. 81 dysregulated metabolites were identified as differential metabolites (adjusted P <0.05, FC≥2 or≤0.5) in positive ion mode and 80 dysregulated metabolites in negative ion mode, indicating a profound metabolic alteration in the lungs under HF condition. In pathway analysis, arachidonic acid metabolism and tryptophan metabolism were identified as the most significant dysregulated metabolic pathways in the lungs from HF beagles.Conclusions: In this study, we identified profound metabolic variation and dysregulated metabolic pathways, which may deepen our understanding on the pathophysiology of the lungs under HF condition from the perspective of metabolism and open new avenues in lung congestion management in HF.

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Level of Arachidonic Acid and State of Peroxidation Processes in Patients with Aspirin-Intolerant Polypous Rhinosinusitis

Galician Medical Journal ◽

10.21802/gmj.2016.4.10 ◽

2016 ◽

Vol 23 (4) ◽

pp. 2016410

Author(s):

Ivanna Koshel

Keyword(s):

Arachidonic Acid ◽

Metabolic Pathways ◽

Acid Metabolism ◽

Serum Proteins ◽

Arachidonic Acid Metabolism ◽

Oxidative Modification ◽

Key Enzyme ◽

Protein Peroxidation ◽

Genetic Block ◽

Peroxidation Processes

The main peculiarity of aspirin-intolerant polypous rhinosinusitis pathogenesis is the presence of “genetic block” of constitutive cyclooxygenase being the key enzyme of the arachidonic acid metabolism. It justifies the necessity of studying its metabolic peculiarities.The objective of the research was to determine the level of arachidonic acid as well as the state of lipid and protein peroxidation processes in patients with aspirin-intolerant polypous rhinosinusitis.Materials and methods. The levels of arachidonic acid, malondialdehyde and oxidative modification of serum proteins were studied in 20 patients with aspirin-intolerant polypous rhinosinusitis and 7 healthy individuals.Results. Significantly elevated levels of arachidonic levels were observed. The search for alternative metabolic pathways stimulated lipid and protein peroxidation processes and led to the increase in the levels of malondialdehyde and oxidative modification of serum proteins. The peculiarities of biochemical changes indicated pro-inflammatory orientation of lipid metabolism.Conclusions. The obtained data confirmed the hypothesis of “genetic block” of the arachidonic acid metabolism as the main pathogenetic component of aspirin-intolerant polypous rhinosinusitis and allowed us to clearly interpret biochemical picture of the disease.

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