Metabolism and function of phospholipids
Dotaz
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- MeSH
- fosfolipidy metabolismus fyziologie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fosfolipidy MeSH
L-serine plays an essential role in a broad range of cellular functions including protein synthesis, neurotransmission, and folate and methionine cycles and synthesis of sphingolipids, phospholipids, and sulphur containing amino acids. A hydroxyl side-chain of L-serine contributes to polarity of proteins, and serves as a primary site for binding a phosphate group to regulate protein function. D-serine, its D-isoform, has a unique role. Recent studies indicate increased requirements for L-serine and its potential therapeutic use in some diseases. L-serine deficiency is associated with impaired function of the nervous system, primarily due to abnormal metabolism of phospholipids and sphingolipids, particularly increased synthesis of deoxysphingolipids. Therapeutic benefits of L-serine have been reported in primary disorders of serine metabolism, diabetic neuropathy, hyperhomocysteinemia, and amyotrophic lateral sclerosis. Use of L-serine and its metabolic products, specifically D-serine and phosphatidylserine, has been investigated for the therapy of renal diseases, central nervous system injury, and in a wide range of neurological and psychiatric disorders. It is concluded that there are disorders in which humans cannot synthesize L-serine in sufficient quantities, that L-serine is effective in therapy of disorders associated with its deficiency, and that L-serine should be classified as a "conditionally essential" amino acid.
- Klíčová slova
- deoxysphingolipids, diabetes, glycine, hyperhocysteinemia, neuropathy, serine supplementation,
- MeSH
- esenciální aminokyseliny MeSH
- fosfolipidy MeSH
- lidé MeSH
- serin * MeSH
- sfingolipidy metabolismus MeSH
- vrozené poruchy metabolismu aminokyselin * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- esenciální aminokyseliny MeSH
- fosfolipidy MeSH
- serin * MeSH
- sfingolipidy MeSH
Every cell cycle iteration culminates with the resolution of a mitotic nucleus into a pair of daughter nuclei, which are distributed between the two daughter cells. In the fission yeast Schizosaccharomyces pombe, the faithful division of a mitotic nucleus depends on unperturbed lipogenesis. Upon genetically or chemically induced perturbation of lipid anabolism, S. pombe cells fail to separate the two daughter nuclei and subsequently initiate lethal cytokinesis resulting in the so-called "cut" terminal phenotype. Evidence supporting a critical role of lipid biogenesis in successful mitosis in S. pombe has been accumulating for almost two decades, but the exact mechanism explaining the reported observations had been elusive. Recently, several studies established a functional link between biosynthesis of structural phospholipids, nuclear membrane growth, and the fidelity of "closed" mitosis in S. pombe. These novel insights suggest a mechanistic explanation for the mitotic defects characteristic for some S. pombe mutants deficient in lipid anabolism and extend our knowledge of metabolic modulation within the context of the cell cycle. In this review, we cover the essential role of lipogenesis in "closed" mitosis, focusing mainly on S. pombe as a model system.
- Klíčová slova
- Schizosaccharomyces pombe, catastrophic mitosis, cell cycle progression, cut phenotype, fission yeast, lipid metabolism,
- MeSH
- fosfolipidy metabolismus MeSH
- jaderný obal metabolismus MeSH
- lipogeneze * MeSH
- membránové lipidy metabolismus MeSH
- mitóza * MeSH
- Schizosaccharomyces růst a vývoj metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- fosfolipidy MeSH
- membránové lipidy MeSH
The life cycle of enveloped viruses is closely linked to host-cell lipids. However, changes in lipid metabolism during infections with the tick-borne encephalitis virus (TBEV) have not been described. TBEV is a medically important orthoflavivirus, which is endemic to many parts of Europe and Asia. In the present study, we performed targeted lipidomics with HPLC-MS/MS to evaluate changes in phospholipid and sphingolipid concentrations in TBEV-infected human neuronal SK-N-SH cells. TBEV infections significantly increased phosphatidylcholine, phosphatidylinositol, and phosphatidylserine levels within 48 h post-infection (hpi). Sphingolipids were slightly increased in dihydroceramides within 24 hpi. Later, at 48 hpi, the contents of sphinganine, dihydroceramides, ceramides, glucosylceramides, and ganglioside GD3 were elevated. On the other hand, sphingosine-1-phosphate content was slightly reduced in TBEV-infected cells. Changes in sphingolipid concentrations were accompanied by suppressed expression of a majority of the genes linked to sphingolipid and glycosphingolipid metabolism. Furthermore, we found that a pharmacological inhibitor of sphingolipid synthesis, fenretinide (4-HPR), inhibited TBEV infections in SK-N-SH cells. Taken together, our results suggested that both structural and signaling functions of lipids could be affected during TBEV infections. These changes might be connected to virus propagation and/or host-cell defense.
- Klíčová slova
- 4-HPR, Fenretinide, Human neuronal cells, Sphingolipids, Targeted lipidomics, Tick-borne encephalitis virus,
- MeSH
- buněčné linie MeSH
- fosfolipidy * metabolismus MeSH
- interakce hostitele a patogenu MeSH
- lidé MeSH
- lipidomika MeSH
- metabolismus lipidů MeSH
- neurony * virologie metabolismus MeSH
- sfingolipidy * metabolismus MeSH
- tandemová hmotnostní spektrometrie MeSH
- viry klíšťové encefalitidy * fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fosfolipidy * MeSH
- sfingolipidy * MeSH
Antisteatotic effects of omega-3 fatty acids (Omega-3) in obese rodents seem to vary depending on the lipid form of their administration. Whether these effects could reflect changes in intestinal metabolism is unknown. Here, we compare Omega-3-containing phospholipids (krill oil; ω3PL-H) and triacylglycerols (ω3TG) in terms of their effects on morphology, gene expression and fatty acid (FA) oxidation in the small intestine. Male C57BL/6N mice were fed for 8 weeks with a high-fat diet (HFD) alone or supplemented with 30 mg/g diet of ω3TG or ω3PL-H. Omega-3 index, reflecting the bioavailability of Omega-3, reached 12.5% and 7.5% in the ω3PL-H and ω3TG groups, respectively. Compared to HFD mice, ω3PL-H but not ω3TG animals had lower body weight gain (-40%), mesenteric adipose tissue (-43%), and hepatic lipid content (-64%). The highest number and expression level of regulated intestinal genes was observed in ω3PL-H mice. The expression of FA ω-oxidation genes was enhanced in both Omega-3-supplemented groups, but gene expression within the FA β-oxidation pathway and functional palmitate oxidation in the proximal ileum was significantly increased only in ω3PL-H mice. In conclusion, enhanced intestinal FA oxidation could contribute to the strong antisteatotic effects of Omega-3 when administered as phospholipids to dietary obese mice.
- Klíčová slova
- Omega-3 index, Omega-3 phospholipids, high-fat diet, krill oil, small intestine,
- MeSH
- dieta s vysokým obsahem tuků * MeSH
- erytrocytární membrána metabolismus MeSH
- Euphausiacea MeSH
- fosfolipidy aplikace a dávkování MeSH
- krevní glukóza analýza MeSH
- mastné kyseliny metabolismus MeSH
- metabolismus lipidů účinky léků MeSH
- myši obézní MeSH
- oleje MeSH
- omega-3 mastné kyseliny aplikace a dávkování MeSH
- oxidace-redukce MeSH
- střeva anatomie a histologie MeSH
- střevní sliznice metabolismus MeSH
- tělesná hmotnost MeSH
- triglyceridy aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fosfolipidy MeSH
- krevní glukóza MeSH
- mastné kyseliny MeSH
- oleje MeSH
- omega-3 mastné kyseliny MeSH
- triglyceridy MeSH
The content of the marine n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is far lower in lean than in fatty seafood. Cod filets contain less than 2g fat per kg, whereof approximately 50% is EPA and DHA. However, a large fraction of these n-3 PUFAs is present in the phospholipid (PL) fraction and may have high bioavailability and capacity to change the endocannabinoid profile. Here we investigated whether exchanging meat from a lean terrestrial animal with cod in a background Western diet would alter the endocannabinoid tone in mice and thereby attenuate obesity development and hepatic lipid accumulation. Accordingly, we prepared iso-caloric diets with 15.1 energy (e) % protein, 39.1 e% fat and 45.8 e% carbohydrates using freeze-dried meat from cod filets or pork sirloins, and using a combination of soybean oil, corn oil, margarine, milk fat, and lard as the fat source. Compared with mice receiving diets containing pork, mice fed cod gained less adipose tissue mass and had a lower content of hepatic lipids. This was accompanied by a lower n-6 to n-3 ratio in liver PLs and in red blood cells (RBCs) in the mice. Furthermore, mice receiving the cod-containing diet had lower circulating levels of the two major endocannabinoids, N-arachidonoylethanolamine and 2-arachidonoylglycerol. Together, our data demonstrate that despite the relatively low content of n-3 PUFAs in cod fillets, the cod-containing diet could exert beneficial metabolic effects.
- Klíčová slova
- Diet, Dietary lipids, Endocannabinoids, Fish oil, Liver, Obesity, Phospholipids,
- MeSH
- algoritmy MeSH
- endokanabinoidy krev MeSH
- erytrocyty metabolismus MeSH
- fosfolipidy metabolismus MeSH
- funkční potraviny MeSH
- Gadus morhua * MeSH
- glyceridy krev MeSH
- játra metabolismus patologie MeSH
- kyseliny arachidonové krev MeSH
- kyseliny mastné omega-6 krev metabolismus MeSH
- maso MeSH
- mastné kyseliny metabolismus MeSH
- metabolismus lipidů * MeSH
- myši inbrední C57BL MeSH
- nealkoholová steatóza jater etiologie metabolismus patologie prevence a kontrola MeSH
- obezita etiologie metabolismus patologie prevence a kontrola MeSH
- omega-3 mastné kyseliny krev metabolismus MeSH
- polynenasycené alkamidy MeSH
- potrava z moře (živočišná) * MeSH
- západní dieta škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- anandamide MeSH Prohlížeč
- endokanabinoidy MeSH
- fosfolipidy MeSH
- glyceridy MeSH
- glyceryl 2-arachidonate MeSH Prohlížeč
- kyseliny arachidonové MeSH
- kyseliny mastné omega-6 MeSH
- mastné kyseliny MeSH
- omega-3 mastné kyseliny MeSH
- polynenasycené alkamidy MeSH
Metformin can reduce cardiovascular risk independent of glycemic control. The mechanisms behind its non-glycemic benefits, which include decreased energy intake, lower blood pressure and improved lipid and fatty acid metabolism, are not fully understood. In our study, metformin treatment reduced myocardial accumulation of neutral lipids-triglycerides, cholesteryl esters and the lipotoxic intermediates-diacylglycerols and lysophosphatidylcholines in a prediabetic rat model (p < 0.001). We observed an association between decreased gene expression and SCD-1 activity (p < 0.05). In addition, metformin markedly improved phospholipid fatty acid composition in the myocardium, represented by decreased SFA profiles and increased n3-PUFA profiles. Known for its cardioprotective and anti-inflammatory properties, metformin also had positive effects on arachidonic acid metabolism and CYP-derived arachidonic acid metabolites. We also found an association between increased gene expression of the cardiac isoform CYP2c with increased 14,15-EET (p < 0.05) and markedly reduced 20-HETE (p < 0.001) in the myocardium. Based on these results, we conclude that metformin treatment reduces the lipogenic enzyme SCD-1 and the accumulation of the lipotoxic intermediates diacylglycerols and lysophosphatidylcholine. Increased CYP2c gene expression and beneficial effects on CYP-derived arachidonic acid metabolites in the myocardium can also be involved in cardioprotective effect of metformin.
- Klíčová slova
- arachidonic acid, cytochrome P450, fatty acid profile, lipotoxic intermediates, metformin, myocardial function, myocardial phospholipids, stearoyl-CoA desaturase,
- MeSH
- bazální metabolismus účinky léků MeSH
- biologické markery krev MeSH
- desaturasy mastných kyselin metabolismus MeSH
- hyperlipoproteinemie typ IV farmakoterapie metabolismus MeSH
- hypoglykemika farmakologie MeSH
- kardiotonika farmakologie MeSH
- krysa rodu Rattus MeSH
- kyselina arachidonová metabolismus MeSH
- mediátory zánětu krev MeSH
- metabolismus lipidů účinky léků MeSH
- metformin farmakologie MeSH
- modely nemocí na zvířatech MeSH
- myokard metabolismus MeSH
- potkani Wistar MeSH
- prediabetes farmakoterapie metabolismus MeSH
- rizikové faktory MeSH
- srdce účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- desaturasy mastných kyselin MeSH
- hypoglykemika MeSH
- kardiotonika MeSH
- kyselina arachidonová MeSH
- mediátory zánětu MeSH
- metformin MeSH
Alcohol-induced oxidative stress is linked to the metabolism of ethanol. Three metabolic pathways of ethanol have been described in the human body so far. They involve the following enzymes: alcohol dehydrogenase, microsomal ethanol oxidation system (MEOS) and catalase. Each of these pathways could produce free radicals which affect the antioxidant system. Ethanol per se, hyperlactacidemia and elevated NADH increase xanthine oxidase activity, which results in the production of superoxide. Lipid peroxidation and superoxide production correlate with the amount of cytochrome P450 2E1. MEOS aggravates the oxidative stress directly as well as indirectly by impairing the defense systems. Hydroxyethyl radicals are probably involved in the alkylation of hepatic proteins. Nitric oxide (NO) is one of the key factors contributing to the vessel wall homeostasis, an important mediator of the vascular tone and neuronal transduction, and has cytotoxic effects. Stable metabolites--nitrites and nitrates--were increased in alcoholics (34.3 +/- 2.6 vs. 22.7 +/- 1.2 micromol/l, p < 0.001). High NO concentration could be discussed for its excitotoxicity and may be linked to cytotoxicity in neurons, glia and myelin. Formation of NO has been linked to an increased preference for and tolerance to alcohol in recent studies. Increased NO biosynthesis also via inducible NO synthase (NOS, chronic stimulation) may contribute to platelet and endothelial dysfunctions. Comparison of chronically ethanol-fed rats and controls demonstrates that exposure to ethanol causes a decrease in NADPH diaphorase activity (neuronal NOS) in neurons and fibers of the cerebellar cortex and superior colliculus (stratum griseum superficiale and intermedium) in rats. These changes in the highly organized structure contribute to the motor disturbances, which are associated with alcohol abuse. Antiphospholipid antibodies (APA) in alcoholic patients seem to reflect membrane lesions, impairment of immunological reactivity, liver disease progression, and they correlate significantly with the disease severity. The low-density lipoprotein (LDL) oxidation is supposed to be one of the most important pathogenic mechanisms of atherogenesis, and antibodies against oxidized LDL (oxLDL) are some kind of epiphenomenon of this process. We studied IgG oxLDL and four APA (anticardiolipin, antiphosphatidylserine, antiphosphatidylethanolamine and antiphosphatidylcholine antibodies). The IgG oxLDL (406.4 +/- 52.5 vs. 499.9 +/- 52.5 mU/ml) was not affected in alcoholic patients, but oxLDL was higher (71.6 +/- 4.1 vs. 44.2 +/- 2.7 micromol/l, p < 0.001). The prevalence of studied APA in alcoholics with mildly affected liver function was higher than in controls, but not significantly. On the contrary, changes of autoantibodies to IgG oxLDL revealed a wide range of IgG oxLDL titers in a healthy population. These parameters do not appear to be very promising for the evaluation of the risk of atherosclerosis. Free radicals increase the oxidative modification of LDL. This is one of the most important mechanisms, which increases cardiovascular risk in chronic alcoholic patients. Important enzymatic antioxidant systems - superoxide dismutase and glutathione peroxidase - are decreased in alcoholics. We did not find any changes of serum retinol and tocopherol concentrations in alcoholics, and blood and plasma selenium and copper levels were unchanged as well. Only the zinc concentration was decreased in plasma. It could be related to the impairment of the immune system in alcoholics. Measurement of these parameters in blood compartments does not seem to indicate a possible organ, e.g. liver deficiency.
- MeSH
- alkoholismus krev MeSH
- aminopeptidasy krev MeSH
- antioxidancia metabolismus MeSH
- autoprotilátky krev účinky léků MeSH
- dospělí MeSH
- ethanol metabolismus farmakologie MeSH
- fosfolipidy imunologie MeSH
- gama-glutamyltransferasa krev účinky léků MeSH
- glutamylaminopeptidasa MeSH
- jaterní testy MeSH
- játra chemie cytologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipoproteiny LDL analýza krev MeSH
- oxid dusnatý metabolismus MeSH
- oxidační stres účinky léků MeSH
- poruchy způsobené alkoholem metabolismus MeSH
- stopové prvky krev MeSH
- studie případů a kontrol MeSH
- volné radikály krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- aminopeptidasy MeSH
- antioxidancia MeSH
- autoprotilátky MeSH
- ethanol MeSH
- fosfolipidy MeSH
- gama-glutamyltransferasa MeSH
- glutamylaminopeptidasa MeSH
- lipoproteiny LDL MeSH
- oxid dusnatý MeSH
- oxidized low density lipoprotein MeSH Prohlížeč
- stopové prvky MeSH
- volné radikály MeSH
Phosphatidylinositol (PI) is the precursor lipid for the minor phosphoinositides (PPIns), which are critical for multiple functions in all eukaryotic cells. It is poorly understood how phosphatidylinositol, which is synthesized in the ER, reaches those membranes where PPIns are formed. Here, we used VT01454, a recently identified inhibitor of class I PI transfer proteins (PITPs), to unravel their roles in lipid metabolism, and solved the structure of inhibitor-bound PITPNA to gain insight into the mode of inhibition. We found that class I PITPs not only distribute PI for PPIns production in various organelles such as the plasma membrane (PM) and late endosomes/lysosomes, but that their inhibition also significantly reduced the levels of phosphatidylserine, di- and triacylglycerols, and other lipids, and caused prominent increases in phosphatidic acid. While VT01454 did not inhibit Golgi PI4P formation nor reduce resting PM PI(4,5)P2 levels, the recovery of the PM pool of PI(4,5)P2 after receptor-mediated hydrolysis required both class I and class II PITPs. Overall, these studies show that class I PITPs differentially regulate phosphoinositide pools and affect the overall cellular lipid landscape.
- Klíčová slova
- Golgi Complex, Membrane Contact Sites, Non-Vesicular Lipid Transport, Phosphatidylinositol, Phospholipase C,
- MeSH
- buněčná membrána metabolismus MeSH
- endozomy metabolismus MeSH
- fosfatidylinositoly * metabolismus MeSH
- HeLa buňky MeSH
- lidé MeSH
- metabolismus lipidů MeSH
- organely metabolismus MeSH
- proteiny přenášející fosfolipidy * metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The influence of an eicosapentaenoic-acid-rich diet, containing 8.1 g cod-liver oil, given daily for two weeks on various parameters of lipid metabolism, the thromboxane formation capacity, platelet function and the serum MDA level was studied in 16 patients with myocardial infarction. The 18:2, 20:3 and 20:4 fatty acid portions of serum phospholipids were significantly decreased, whereas the 20:5 and 22:6 portions were significantly elevated. Serum total cholesterol, LDL cholesterol and the thromboxane formation capacity were significantly increased. Serum triglycerides, HDL cholesterol, the prostacyclin blocking activity of LDL, and several parameters of platelet function were unchanged, the platelet count was significantly depressed. As compared to those of healthy persons, the serum MDA levels in myocardial infarction patients were significantly increased both before and after cod-liver oil ingestion. A possible correlation between the elevated serum levels of MDA and total cholesterol, LDL cholesterol as well as thromboxane formation capacity and the cod-liver oil treatment in patients with myocardial infarction is discussed.
- MeSH
- agregace trombocytů * MeSH
- cholesterol krev MeSH
- infarkt myokardu krev terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipidy krev MeSH
- lipoproteiny krev MeSH
- malonáty krev MeSH
- malondialdehyd krev MeSH
- rybí oleje aplikace a dávkování MeSH
- rybí tuk aplikace a dávkování MeSH
- thromboxany krev MeSH
- triglyceridy krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cholesterol MeSH
- lipidy MeSH
- lipoproteiny MeSH
- malonáty MeSH
- malondialdehyd MeSH
- rybí oleje MeSH
- rybí tuk MeSH
- thromboxany MeSH
- triglyceridy MeSH