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Molecular Plant-microbe Interactions :... Jun 2022Arbuscular mycorrhizal fungi (AMF) colonize roots, where they provide nutrients in exchange for sugars and lipids. Because AMF lack genes for cytosolic fatty acid de...
Arbuscular mycorrhizal fungi (AMF) colonize roots, where they provide nutrients in exchange for sugars and lipids. Because AMF lack genes for cytosolic fatty acid de novo synthase (FAS), they depend on host-derived fatty acids. AMF colonization is accompanied by expression of specific lipid genes and synthesis of -2 monoacylglycerols (MAGs). It is unknown how host-derived fatty acids are taken up by AMF. We describe the characterization of two AMP-binding domain protein genes from , and , with sequence similarity to (). Uptake of C-myristic acid (14:0) and, to a lesser extent, C-palmitic acid (16:0) was enhanced after expression of or in Δ cells. The uptake of H-labeled fatty acids from H-myristoylglycerol or H-palmitoylglycerol was also increased after and expression in Δ, but intact H-MAGs were not detected. and expression was induced in colonized roots compared with extraradical mycelium. C-label in the AMF-specific palmitvaccenic acid (16:1Δ11) and eicosatrienoic acid (20:3) were detected in colonized roots only when C-acetate was supplemented but not C-fatty acids, demonstrating that de novo synthesized, host-derived fatty acids are rapidly taken up by from the roots. The results show that RiFAT1 and RiFAT2 are involved in the uptake of myristic acid (14:0) and palmitic acid (16:0), while fatty acids from MAGs are only taken up after hydrolysis. Therefore, the two proteins might be involved in fatty acid import into the fungal arbuscules in colonized roots.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
Topics: Adenosine Monophosphate; Carrier Proteins; Fatty Acid Transport Proteins; Fatty Acids; Fungi; Glomeromycota; Mycorrhizae; Myristic Acids; Palmitic Acids; Plant Roots; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 35285673
DOI: 10.1094/MPMI-01-22-0026-R -
Clinica Chimica Acta; International... Mar 2024Coronary heart disease (CHD) is the most important complication of type 2 diabetes mellitus (T2DM) and the leading cause of death. Identifying the risk of CHD in T2DM...
Machine learning reveals serum myristic acid, palmitic acid and heptanoylcarnitine as biomarkers of coronary artery disease risk in patients with type 2 diabetes mellitus.
BACKGROUND
Coronary heart disease (CHD) is the most important complication of type 2 diabetes mellitus (T2DM) and the leading cause of death. Identifying the risk of CHD in T2DM patients is important for early clinical intervention.
METHODS
A total of 213 participants, including 81 healthy controls (HCs), 69 T2DM patients and 63 T2DM patients complicated with CHD were recruited in this study. Serum metabolomics were conducted by using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Demographic information and clinical laboratory test results were also collected.
RESULTS
Metabolic phenotypes were significantly altered among HC, T2DM and T2DM-CHD. Acylcarnitines were the most disturbed metabolites between T2DM patients and HCs. Lower levels of bile acids and higher levels of fatty acids in serum were closely associated with CHD risk in T2DM patients. Artificial neural network model was constructed for the discrimination of T2DM and T2DM complicated with CHD based on myristic acid, palmitic acid and heptanoylcarnitine, with accuracy larger than 0.95 in both training set and testing set.
CONCLUSION
Altogether, these findings suggest that myristic acid, palmitic acid and heptanoylcarnitine have a good prospect for the warning of CHD complications in T2DM patients, and are superior to traditional lipid, blood glucose and blood pressure indicators.
Topics: Humans; Coronary Artery Disease; Diabetes Mellitus, Type 2; Palmitic Acid; Tandem Mass Spectrometry; Myristic Acid; Arteries; Biomarkers; Machine Learning; Carnitine
PubMed: 38438006
DOI: 10.1016/j.cca.2024.117852 -
Progress in Lipid Research Jan 2022Protein myristoylation is a C14 fatty acid modification found in all living organisms. Myristoylation tags either the N-terminal alpha groups of cysteine or glycine... (Review)
Review
Protein myristoylation is a C14 fatty acid modification found in all living organisms. Myristoylation tags either the N-terminal alpha groups of cysteine or glycine residues through amide bonds or lysine and cysteine side chains directly or indirectly via glycerol thioester and ester linkages. Before transfer to proteins, myristate must be activated into myristoyl coenzyme A in eukaryotes or, in bacteria, to derivatives like phosphatidylethanolamine. Myristate originates through de novo biosynthesis (e.g., plants), from external uptake (e.g., human tissues), or from mixed origins (e.g., unicellular organisms). Myristate usually serves as a molecular anchor, allowing tagged proteins to be targeted to membranes and travel across endomembrane networks in eukaryotes. In this review, we describe and discuss the metabolic origins of protein-bound myristate. We review strategies for in vivo protein labeling that take advantage of click-chemistry with reactive analogs, and we discuss new approaches to the proteome-wide discovery of myristate-containing proteins. The machineries of myristoylation are described, along with how protein targets can be generated directly from translating precursors or from processed proteins. Few myristoylation catalysts are currently described, with only N-myristoyltransferase described to date in eukaryotes. Finally, we describe how viruses and bacteria hijack and exploit myristoylation for their pathogenicity.
Topics: Acyltransferases; Fatty Acids; Humans; Myristic Acid; Protein Processing, Post-Translational; Proteins
PubMed: 34793862
DOI: 10.1016/j.plipres.2021.101139 -
Metabolism: Clinical and Experimental Jun 2022Obesity is an established risk factor for higher SARS-CoV-2 viral loads, severe COVID-19 pneumonia requiring hospitalization, and worse outcomes. However, the underlying...
OBJECTIVE
Obesity is an established risk factor for higher SARS-CoV-2 viral loads, severe COVID-19 pneumonia requiring hospitalization, and worse outcomes. However, the underlying mechanisms for the increased risk are not well understood. SARS-CoV-2 is a respiratory virus with the primary route of entry through the lungs, where the Spike protein of SARS-CoV-2 binds to the ACE2 receptor on pneumocytes. Lung surfactant produced by type II pneumocytes plays a major role in respiratory defense against infections. Surfactant predominantly contains lipids, especially phosphatidylcholines (PC), and obesity is characterized by aberrant lipid metabolism. We hypothesized that altered lipid composition in lung surfactant in obesity may promote SARS-CoV-2 infection, leading to severe COVID-19 disease.
METHODS
Lipidomic analysis of lung tissue and bronchoalveolar lavage fluid (BALF) was performed using LC-MS/MS. The effects of PCs on SARS-CoV-2 pseudovirus infection were studied in HEK293T cells with ACE2 overexpression and in Vero-E6 cells with endogenous ACE2 expression. For the cell-cell fusion assay, HEK293T-ACE2 and HEK293T expressing SARS-CoV-2 Spike/eGFP were used as the target and effector cells, respectively.
RESULTS
Lipidomic analysis revealed that myristic acid-containing dimyristoyl-PC (DMPC) and palmitoylmyristoyl-PC (PMPC) were reduced in lung tissue and BALF from high fat diet-induced obese mice. DMPC and PMPC markedly inhibited wild type and D614G mutant SARS-CoV-2 infection in HEK293T-ACE2 and Vero-E6 cells. Feeding obese mice with trimyristin, the triglycerides of myristic acid, increased DMPC and PMPC levels in lung surfactant. Lipid extract from BALF of trimyristin-treated obese mice mitigated the elevated wild type and D614G mutant SARS-CoV-2 infection. The inhibitory effects of DMPC and PMPC on SARS-CoV-2 infection were reversed by cholesterol.
CONCLUSIONS
The reduced DMPC and PMPC in lung surfactant may promote SARS-CoV-2 infection. Increasing DMPC and PMPC in lung surfactant could be an innovative strategy for preventing and treating severe COVID-19 disease in obesity.
Topics: Angiotensin-Converting Enzyme 2; Animals; COVID-19; Chromatography, Liquid; Dimyristoylphosphatidylcholine; HEK293 Cells; Humans; Lung; Mice; Myristic Acid; Obesity; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Surface-Active Agents; Tandem Mass Spectrometry
PubMed: 35311662
DOI: 10.1016/j.metabol.2022.155181 -
Advances in Nutrition (Bethesda, Md.) Dec 2022This systematic review and meta-analysis was conducted to pool findings of cohort studies that investigated hazards of type 2 diabetes mellitus (T2DM) in relation to... (Meta-Analysis)
Meta-Analysis
This systematic review and meta-analysis was conducted to pool findings of cohort studies that investigated hazards of type 2 diabetes mellitus (T2DM) in relation to intakes of SFAs. A systematic search was conducted in the PubMed, Scopus, and Embase databases up to June 2021 to find eligible studies. Review articles or commentaries, clinical trials, cross-sectional studies, studies on gestational or type 1 diabetes patients, animal studies, articles with no access to full-texts, articles published in non-English languages, and articles with missing critical data needed for the systematic review were excluded from the meta-analysis. A random-effects model was used to combine study-specific results. Thirteen cohort studies with 361,686 participants and 11,865 T2DM events were included. Dietary total SFA intake, as well as dietary palmitic acid (PA) or stearic acid (SA) were not associated with risk of T2DM when the highest was compared with the lowest intake category (HR = 0.99; 95% CI: 0.91, 1.09; n = 13 for total SFAs; HR = 0.96; 95% CI: 0.79, 1.15; n = 4 for PA; and HR = 1.08; 95% CI: 0.79, 1.49; n = 4 for SA). However, the risk of T2DM decreased by 11% in the highest compared with the lowest category of dietary lauric acid (HR = 0.89; 95% CI: 0.82, 0.97; n = 2), and by 17% in the highest compared with lowest category of dietary myristic acid (MA) (HR = 0.83; 95% CI: 0.74, 0.92; n = 3). There was evidence of publication bias among studies on dietary total SFAs and T2DM. Our results indicated no significant association between dietary total SFA and risk of T2DM. However, dietary intake of MA was negatively associated with developing T2DM.
Topics: Animals; Humans; Diabetes Mellitus, Type 2; Cross-Sectional Studies; Prospective Studies; Cohort Studies; Fatty Acids; Risk Factors
PubMed: 36056919
DOI: 10.1093/advances/nmac071 -
Prague Medical Report 2019Myristic acid was identified as a metabolite with the highest diagnostic sensitivity and specificity in the metabolome of patients with bacteraemia. Subsequently, its...
Myristic acid was identified as a metabolite with the highest diagnostic sensitivity and specificity in the metabolome of patients with bacteraemia. Subsequently, its significant decrease was observed in patients in septic shock not responding to treatment. In our study we have captured myristic acid serum level kinetics in 96 hours following accidental intravenous self-administration of eubiotic Hylak forte causing infection-like systemic inflammatory response syndrome (SIRS). To our knowledge, this is the first time the kinetics of myristic acid levels is presented in a septic patient. Myristic acid was evaluated in comparison with other inflammatory biomarkers and with its level in a control group of healthy subjects. Myristic acid levels during septic response were significantly elevated in comparison with the control group. The peak level was recorded almost immediately after the insult with a gradual decrease within 96 hours. Myristic acid appears to be a promising biomarker in sepsis diagnostics, further research by our group into this topic is ongoing.
Topics: Biomarkers; Humans; Inflammation; Kinetics; Myristic Acid; Sepsis; Shock, Septic; Syndrome
PubMed: 31586509
DOI: 10.14712/23362936.2019.15 -
Antioxidants (Basel, Switzerland) Apr 2020The aim of this study was to evaluate the extraction efficiency of polyphenols from crude pollen by an ultrasonic process. Prior to the polyphenols extraction, the crude...
The aim of this study was to evaluate the extraction efficiency of polyphenols from crude pollen by an ultrasonic process. Prior to the polyphenols extraction, the crude pollen was defatted. The extraction from defatted pollen was carried out by varying four extraction parameters: ultrasonic amplitude (20%, 60% and 100%), solid/liquid ratio (10 g/L, 20 g/L and 30 g/L), temperature (35, 50 and 65 °C) and time (10, 20 and 30 min). The extracts were analyzed in terms of extraction yield (%), total phenolic content (TPC) and total flavones content (TFC). The extracted oil was analyzed in terms of fatty acids composition; myristic acid (159.1 µg × g) and cis-14-pentadecenoic acid (106.6 µg·g) were found in the highest amount in the pollen oil. The optimum conditions of extraction were determined and were, as follows: 100% amplitude of ultrasonic treatment, 30 g/L solid/liquid ratio, 40.85 °C and 14.30 min, which led to the extraction of 366.1 mg GAE/L of TPC and 592.2 mg QE/g of TFC, and also to an extraction yield of 1.92%.
PubMed: 32316244
DOI: 10.3390/antiox9040322 -
Journal of Colloid and Interface Science Jan 2018In fatty acid systems, the role of the nature of the counter-ion on their solubility is well described. However, the effect of the molar ratio (R) between the fatty acid...
HYPOTHESIS
In fatty acid systems, the role of the nature of the counter-ion on their solubility is well described. However, the effect of the molar ratio (R) between the fatty acid and its counter-ion is less explored. We investigated the effect of R as a function of the temperature in aqueous solution between myristic acid and two organic amines under hydroxide form: tetramethylammonium (TMAOH) and benzyltrimethylammonium hydroxide (BTAOH). We compare with the results previously obtained for choline hydroxide as counter-ion (Arnould et al., 2015).
EXPERIMENTS
We characterized the phase behavior by coupling phase-contrast microscopy, SANS, DSC and WAXS experiments. The myristic acid ionization state was determined by pH, conductivity and infra-red spectroscopy measurements.
FINDINGS
Our results highlight that R tunes the phase behavior. The amount of hydroxide groups in solution fixes the ionization state of the fatty acids, which governs the headgroup interactions. At low R, the counter-ion hydrophobicity plays a role on the phase behavior: TMAOH and choline hydroxide shows a broad polymorphism (facetted and unilamellar vesicles, lamellar phases) due to their hydrophilicity while the more hydrophobic BTAOH gives fatty acid crystals at low temperatures and vesicles at high temperatures. At high R, spherical micelles are observed for all counter-ions.
PubMed: 28942163
DOI: 10.1016/j.jcis.2017.09.058 -
The Journal of Antibiotics May 2019Listeria monocytogenes (L. monocytogenes), an important food-borne pathogenic microorganism, has resistance immune function to many commonly used drugs. Myristic acid is...
Listeria monocytogenes (L. monocytogenes), an important food-borne pathogenic microorganism, has resistance immune function to many commonly used drugs. Myristic acid is a traditional Chinese herbal medicine, but it has been rarely used as a food additive, limiting the development of natural food preservatives. In this study, the antibacterial activity and mechanism of myristic acid against L. monocytogenes were studied. The minimum inhibitory concentration (MIC) of myristic acid against 13 L. monocytogenes strains ranged from 64 to 256 μg ml. The time-kill assay demonstrated that when myristic acid was added to dairy products, flow cytometry confirmed that myristic acid influenced cell death and inhibited the growth of L. monocytogenes. Transmission electron microscopy (TEM), scanning electron microscopy (SEM), and NPN uptake studies illustrated that myristic acid changed the bacterial morphology and membrane structure of L. monocytogenes, which led to rapid cell death. Myristic acid could bind to DNA and lead to changes in DNA conformation and structure, as identified by fluorescence spectroscopy. Our studies provide additional evidence to support myristic acid being used as a natural antibacterial agent and also further fundamental understanding of the modes of antibacterial action.
Topics: Animals; Anti-Bacterial Agents; Cell Membrane; Disease Transmission, Infectious; Flow Cytometry; Listeria monocytogenes; Microbial Sensitivity Tests; Microbial Viability; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Milk; Myristic Acid; Nucleic Acid Conformation; Spectrometry, Fluorescence
PubMed: 30787402
DOI: 10.1038/s41429-019-0152-5 -
Molecular Omics Oct 2023Parkinson's disease (PD) is a serious neurodegenerative disorder wherein changes in metabolites related to lipids, glutathione, and energy metabolism occur. Currently,...
Parkinson's disease (PD) is a serious neurodegenerative disorder wherein changes in metabolites related to lipids, glutathione, and energy metabolism occur. Currently, metabolite changes in PD have been reported, yet their role in the prognosis of disease remains poorly understood. Functional metabolites can be used to diagnose diseases, especially PD, and can exert neuroprotective effects. This study used a PD animal model and a lipopolysaccharide (LPS)-mediated inflammatory response model (using the BV-2 mouse microglial cell line) to identify functional metabolites that can identify important metabolic disorders during PD, and comprehensively evaluated their profiles using a metabolomics-based approach. Our results showed that co-treatment with myristic acid and heptadecanoic acid downregulated the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in BV-2 cells. Additionally, myristic acid and 10 μM heptadecanoic acid significantly inhibited the LPS-induced inflammatory response through the nuclear factor-κB pathway in BV-2 microglial cells, which provides a potential approach for PD treatment. Myristic acid and heptadecanoic acid were the active metabolites found by active metabolomics technology, but at present, there is no research report about their function for PD treatment, and our findings offer a novel research strategy for PD diagnosis and treatment.
Topics: Mice; Animals; NF-kappa B; Lipopolysaccharides; Microglia; Myristic Acid; Anti-Inflammatory Agents; Parkinson Disease
PubMed: 37466104
DOI: 10.1039/d3mo00063j