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Biochimica Et Biophysica Acta Oct 2012The oxidation of lipids has long been a topic of interest in biological and food sciences, and the fundamental principles of non-enzymatic free radical attack on... (Review)
Review
The oxidation of lipids has long been a topic of interest in biological and food sciences, and the fundamental principles of non-enzymatic free radical attack on phospholipids are well established, although questions about detail of the mechanisms remain. The number of end products that are formed following the initiation of phospholipid peroxidation is large, and is continually growing as new structures of oxidized phospholipids are elucidated. Common products are phospholipids with esterified isoprostane-like structures and chain-shortened products containing hydroxy, carbonyl or carboxylic acid groups; the carbonyl-containing compounds are reactive and readily form adducts with proteins and other biomolecules. Phospholipids can also be attacked by reactive nitrogen and chlorine species, further expanding the range of products to nitrated and chlorinated phospholipids. Key to understanding the mechanisms of oxidation is the development of advanced and sensitive technologies that enable structural elucidation. Tandem mass spectrometry has proved invaluable in this respect and is generally the method of choice for structural work. A number of studies have investigated whether individual oxidized phospholipid products occur in vivo, and mass spectrometry techniques have been instrumental in detecting a variety of oxidation products in biological samples such as atherosclerotic plaque material, brain tissue, intestinal tissue and plasma, although relatively few have achieved an absolute quantitative analysis. The levels of oxidized phospholipids in vivo is a critical question, as there is now substantial evidence that many of these compounds are bioactive and could contribute to pathology. The challenges for the future will be to adopt lipidomic approaches to map the profile of oxidized phospholipid formation in different biological conditions, and relate this to their effects in vivo. This article is part of a Special Issue entitled: Oxidized phospholipids-their properties and interactions with proteins.
Topics: Animals; Humans; Lipid Peroxidation; Models, Biological; Organ Specificity; Oxidation-Reduction; Phospholipids
PubMed: 22342938
DOI: 10.1016/j.bbamem.2012.02.002 -
Scientific Reports Jun 2017Human milk fat contains high concentrations of medium-chained fatty acids (MCFA) and triacylglycerols emulsified by a sphingomyelin-rich phospholipid membrane (milk...
Human milk fat contains high concentrations of medium-chained fatty acids (MCFA) and triacylglycerols emulsified by a sphingomyelin-rich phospholipid membrane (milk phospholipids, MPL). Infant formula comprises mainly long-chained fatty acids (LCFA) emulsified with dairy proteins and soy lecithin (SL) lacking sphingomyelin. Sphingomyelin content and saturation level of phospholipids affect the gut lipase activity, which alters the concentrations of lipid hydrolysis products in ileum and colon, and hereby putatively affects the competitive advantage of specific gut bacteria. Thus, differences in phospholipid and FA composition may modulate the establishment of the gut microbiota. We investigated effects of fatty acid (FA) composition and emulsification (MPL vs SL) ingested during establishment of human gut microbiota in germ-free mice, and found that cecal microbiotas from mice given MCFA-rich emulsions were characterized by high relative abundances of Bacteroidaceae and Desulfovibrionaceae, while LCFA-rich emulsions caused higher abundances of Enterobacteriaceae, Erysipelotrichaceae, Coriobacteriaceae and Enterococcaceae. Consumption of SL-emulsified lipids skewed the community towards more Enterococcaceae and Enterobacteriaceae, while MPL increased Bacteroidaceae, Desulfovibrionaceae, Rikkenellaceae and Porphyromonadaceae. Intake of SL increased cecal concentrations of iso-valeric and iso-butyric acids. This suggests that fat-type and emulsifiers applied in infant formula may have distinct effects on the establishment of the gut microbiota in formula-fed infants.
Topics: Animals; Fatty Acids; Female; Gastrointestinal Microbiome; Humans; Infant Formula; Lower Gastrointestinal Tract; Male; Mice; Phospholipids
PubMed: 28638093
DOI: 10.1038/s41598-017-04298-0 -
Scientific Reports Feb 2021The human hepatoblastoma cell line, HepG2, has been used for investigating a wide variety of physiological and pathophysiological processes. However, less information is...
The human hepatoblastoma cell line, HepG2, has been used for investigating a wide variety of physiological and pathophysiological processes. However, less information is available about the phospholipid metabolism in HepG2 cells. In the present report, to clarify the relationship between cell growth and phospholipid metabolism in HepG2 cells, we examined the phospholipid class compositions of the cells and their intracellular organelles by using enzymatic fluorometric methods. In HepG2 cells, the ratios of all phospholipid classes, but not the ratio of cholesterol, markedly changed with cell growth. Of note, depending on cell growth, the phosphatidic acid (PA) ratio increased and phosphatidylcholine (PC) ratio decreased in the nuclear membranes, the sphingomyelin (SM) ratio increased in the microsomal membranes, and the phosphatidylethanolamine (PE) ratio increased and the phosphatidylserine (PS) ratio decreased in the mitochondrial membranes. Moreover, the mRNA expression levels of enzymes related to PC, PE, PS, PA, SM and cardiolipin syntheses changed during cell growth. We suggest that the phospholipid class compositions of organellar membranes are tightly regulated by cell growth. These findings provide a basis for future investigations of cancer cell growth and lipid metabolism.
Topics: Cell Membrane; Cell Proliferation; Hep G2 Cells; Humans; Lipid Metabolism; Organelles; Phosphatidylcholines; Phosphatidylserines; Phospholipids
PubMed: 33526799
DOI: 10.1038/s41598-021-81733-3 -
Nutrients Jun 2022(1) Background: Changes in phospholipid (phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine, i.e., PC, PE and PS) composition with age in the...
(1) Background: Changes in phospholipid (phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine, i.e., PC, PE and PS) composition with age in the mitochondrial and microsomal membranes of the human cerebellum and motor cortex were examined and compared to previous analyses of the prefrontal cortex, hippocampus and entorhinal cortex. (2) Methods: Nano-electrospray ionization on a hybrid triple quadrupole−linear ion trap mass spectrometer was used to analyse the brain regions of subjects aged 18−104 years. (3) Results: With age, the cerebellum showed many changes in the major phospholipids (>10% of the phospholipid class). In both membrane types, these included increases in PE 18:0_22:6 and PS 18:0_22:6, decreases in PE 18:0_20:4 and PS 18:0_18:1 and an increase in PC 16:0_16:0 (microsomal membrane only). In addition, twenty-one minor phospholipids also changed. In the motor cortex, only ten minor phospholipids changed with age. With age, the acyl composition of the membranes in the cerebellum increased in docosahexaenoic acid (22:6) and decreased in the arachidonic (20:4) and adrenic (22:4) acids. A comparison of phospholipid changes in the cerebellum, motor cortex and other brain areas is provided. (4) Conclusions: The cerebellum is exceptional in the large number of major phospholipids that undergo changes (with consequential changes in acyl composition) with age, whereas the motor cortex is highly resistant to change.
Topics: Aging; Cerebellum; Humans; Motor Cortex; Phosphatidylcholines; Phosphatidylserines; Phospholipids
PubMed: 35745225
DOI: 10.3390/nu14122495 -
International Journal of Molecular... Oct 2019The main phospholipid (MPL) of DSM 1728 was isolated, purified and physico-chemically characterized by differential scanning calorimetry (DSC)/differential thermal... (Review)
Review
The main phospholipid (MPL) of DSM 1728 was isolated, purified and physico-chemically characterized by differential scanning calorimetry (DSC)/differential thermal analysis (DTA) for its thermotropic behavior, alone and in mixtures with other lipids, cholesterol, hydrophobic peptides and pore-forming ionophores. Model membranes from MPL were investigated; black lipid membrane, Langmuir-Blodgett monolayer, and liposomes. Laboratory results were compared to computer simulation. MPL forms stable and resistant liposomes with highly proton-impermeable membrane and mixes at certain degree with common bilayer-forming lipids. Monomeric bacteriorhodopsin and ATP synthase from were co-reconstituted and light-driven ATP synthesis measured. This review reports about almost four decades of research on membrane and its MPL as well as transfer of this research to species recently isolated from Indonesian volcanoes.
Topics: Archaeal Proteins; Calorimetry, Differential Scanning; Computer Simulation; Differential Thermal Analysis; Glycosylation; Liposomes; Phospholipids; Thermoplasma
PubMed: 31640225
DOI: 10.3390/ijms20205217 -
Bioanalysis Jul 2018
Topics: Metabolomics; Phospholipids
PubMed: 29987935
DOI: 10.4155/bio-2018-0098 -
Journal of Lipid Research Apr 2009This review presents an overview of mammalian phospholipid synthesis and the cellular locations of the biochemical activities that produce membrane lipid molecular... (Review)
Review
This review presents an overview of mammalian phospholipid synthesis and the cellular locations of the biochemical activities that produce membrane lipid molecular species. The generalized endoplasmic reticulum compartment is a central site for membrane lipid biogenesis, and examples of the emerging relationships between alterations in lipid composition, regulation of membrane lipid biogenesis, and cellular secretory function are discussed.
Topics: Animals; Endoplasmic Reticulum; Golgi Apparatus; Membrane Lipids; Phospholipids
PubMed: 18952570
DOI: 10.1194/jlr.R800049-JLR200 -
Biochimica Et Biophysica Acta.... Mar 2021As the largest membrane organelle, the endoplasmic reticulum (ER) is the main location for protein preliminary processing and phospholipid synthesis. Phospholipid...
As the largest membrane organelle, the endoplasmic reticulum (ER) is the main location for protein preliminary processing and phospholipid synthesis. Phospholipid bilayer is the main component of the ER, so it plays an intuitively important role in the steady state of protein synthesis in the ER. Despite of their importance, relationship between phospholipid homeostasis and protein processing in Aspergillus niger remains poorly understood. In this study, phosphatidyl ethanolamine (PE)/phosphatidyl choline (PC) and phosphatidyl acid (PA) metabolic mutants and ER protein processing mutants were established by knockout the key genes in phospholipid synthesis or UPR effector hacA. Based on global transcriptome and lipidome analysis, the relationship between the phospholipids imbalance and ER protein secretory imbalance was revealed as followed: The cells compensate for the damage caused by ER protein secretory deficiency or phospholipid deficiency from enhancing the protein processing and the synthesis of phospholipids at the transcription level, therefore phospholipid deficiency (Δopi3) and continuous activation of UPR (hacAi) have a synergistic effect in promoting protein secretion and phospholipid biosynthesis. At the same time, the metabolic deficiencies of phospholipid homeostasis and the processing deficiencies of ER protein will also cause cells sensitive to oxidative stress, cell wall inhibition and DNA damage.
Topics: Aspergillus niger; Endoplasmic Reticulum; Fungal Proteins; Phospholipids
PubMed: 33309775
DOI: 10.1016/j.bbamem.2020.183530 -
Biophysical Journal Nov 2022Phospholipid bilayers are liquid-crystalline materials whose intermolecular interactions at mesoscopic length scales have key roles in the emergence of membrane physical...
Phospholipid bilayers are liquid-crystalline materials whose intermolecular interactions at mesoscopic length scales have key roles in the emergence of membrane physical properties. Here we investigated the combined effects of phospholipid polar headgroups and acyl chains on biophysical functions of membranes with solid-state H NMR spectroscopy. We compared the structural and dynamic properties of phosphatidylethanolamine and phosphatidylcholine with perdeuterated acyl chains in the solid-ordered (s) and liquid-disordered (l) phases. Our analysis of spectral lineshapes of 1,2-diperdeuteriopalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE-d) and 1,2-diperdeuteriopalmitoyl-sn-glycero-3-phosphocholine (DPPC-d) in the s (gel) phase indicated an all-trans rotating chain structure for both lipids. Greater segmental order parameters (S) were observed in the l (liquid-crystalline) phase for DPPE-d than for DPPC-d membranes, while their mixtures had intermediate values irrespective of the deuterated lipid type. Our results suggest the S profiles of the acyl chains are governed by methylation of the headgroups and are averaged over the entire system. Variations in the acyl chain molecular dynamics were further investigated by spin-lattice (R) and quadrupolar-order relaxation (R) measurements. The two acyl-perdeuterated lipids showed distinct differences in relaxation behavior as a function of the order parameter. The R rates had a square-law dependence on S, implying collective mesoscopic dynamics, with a higher bending rigidity for DPPE-d than for DPPC-d lipids. Remodeling of lipid average and dynamic properties by methylation of the headgroups thus provides a mechanism to control the actions of peptides and proteins in biomembranes.
Topics: Phospholipids; 1,2-Dipalmitoylphosphatidylcholine; Phosphatidylcholines; Magnetic Resonance Spectroscopy; Lipid Bilayers
PubMed: 36088534
DOI: 10.1016/j.bpj.2022.09.005 -
The Journal of Clinical Investigation Sep 2023The liver has a high demand for phosphatidylcholine (PC), particularly in overnutrition, where reduced phospholipid levels have been implicated in the development of...
The liver has a high demand for phosphatidylcholine (PC), particularly in overnutrition, where reduced phospholipid levels have been implicated in the development of nonalcoholic fatty liver disease (NAFLD). Whether other pathways exist in addition to de novo PC synthesis that contribute to hepatic PC pools remains unknown. Here, we identified the lysophosphatidylcholine (LPC) transporter major facilitator superfamily domain containing 2A (Mfsd2a) as critical for maintaining hepatic phospholipid pools. Hepatic Mfsd2a expression was induced in patients having NAFLD and in mice in response to dietary fat via glucocorticoid receptor action. Mfsd2a liver-specific deficiency in mice (L2aKO) led to a robust nonalcoholic steatohepatitis-like (NASH-like) phenotype within just 2 weeks of dietary fat challenge associated with reduced hepatic phospholipids containing linoleic acid. Reducing dietary choline intake in L2aKO mice exacerbated liver pathology and deficiency of liver phospholipids containing polyunsaturated fatty acids (PUFAs). Treating hepatocytes with LPCs containing oleate and linoleate, two abundant blood-derived LPCs, specifically induced lipid droplet biogenesis and contributed to phospholipid pools, while LPC containing the omega-3 fatty acid docosahexaenoic acid (DHA) promoted lipid droplet formation and suppressed lipogenesis. This study revealed that PUFA-containing LPCs drive hepatic lipid droplet formation, suppress lipogenesis, and sustain hepatic phospholipid pools - processes that are critical for protecting the liver from excess dietary fat.
Topics: Animals; Mice; Phospholipids; Non-alcoholic Fatty Liver Disease; Liver; Lysophospholipids; Phosphatidylcholines; Dietary Fats; Overnutrition
PubMed: 37463052
DOI: 10.1172/JCI171267