Lipids
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"Descrizione" about Lipids by admin (19344 pt) | 2024-Sep-06 21:36 |
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Lipids are a diverse group of organic compounds that are insoluble in water but soluble in organic solvents. They play crucial roles in biological systems, including energy storage, cellular structure, and signaling.
Chemical Composition and Structure:
Lipids include several classes of molecules:
Fatty Acids: Long hydrocarbon chains with a carboxyl group at one end. They can be saturated (no double bonds) or unsaturated (one or more double bonds).
Triglycerides: Composed of three fatty acids esterified to a glycerol molecule. They are the primary form of stored energy in animals and plants.
Phospholipids: Consist of two fatty acids, a glycerol, and a phosphate group. They are major components of cell membranes.
Steroids: Lipids with a characteristic four-ring structure, including cholesterol and hormones such as testosterone and estrogen.
Waxes: Long-chain fatty acids esterified to long-chain alcohols, serving as protective coatings on plants and animals.
Physical Properties:
Production Process:
Lipids are produced through:
Applications:
Environmental and Safety Considerations:
Lipids are generally safe and biodegradable. However, it is essential to ensure that they are sourced sustainably and free from contaminants. Some lipid-derived products may cause allergic reactions or sensitivities in certain individuals, so testing is recommended when used in food or personal care products.
References__________________________________________________________________________
Pandey V, Kohli S. Lipids and Surfactants: The Inside Story of Lipid-Based Drug Delivery Systems. Crit Rev Ther Drug Carrier Syst. 2018;35(2):99-155. doi:10.1615/CritRevTherDrugCarrierSyst.2018016710. PMID: 29717664.
Abstract. In the bioavailability enhancement of poorly aqueous soluble drugs, self-emulsifying/microemulsifying drug delivery systems (SEDDS/SMEDDS) are isotropic mixtures of oils, surfactants, solvents, and cosolvents/surfactants that have gained immense popularity because of their self-emulsification ability. This characteristic relies on some critical parameters such as surfactant concentration, oil-to-surfactant ratio, polarity of the emulsion, droplet size and charge, which are acquired from an amalgamation of appropriate excipients. The fabrication of this combination is of utmost importance for formulation scientists. Hence, to explore the potential of such a delivery system, standardized guidelines for excipients must be developed to address bioavailability issues. In the present review, we summarize the approaches to selecting the most suitable lipid(s)-based drug delivery system, including characterization, especially for oral delivery, of both physicochemical and biopharmaceutical aspects and properties of assorted excipients as well as the related patent reports.
Lambert DM. Rationale and applications of lipids as prodrug carriers. Eur J Pharm Sci. 2000 Oct;11 Suppl 2:S15-27. doi: 10.1016/s0928-0987(00)00161-5. PMID: 11033424.
Abstract. Lipidic prodrugs, also called drug-lipid conjugates, have the drug covalently bound to a lipid moiety, such as a fatty acid, a diglyceride or a phosphoglyceride. Drug-lipid conjugates have been prepared in order to take advantage of the metabolic pathways of lipid biochemistry, allowing organs to be targeted or delivery problems to be overcome. Endogenous proteins taking up fatty acids from the blood stream can be targeted to deliver the drug to the heart or liver. For glycerides, the major advantage is the modification of the pharmacokinetic behavior of the drug. In this case, one or two fatty acids of a triglyceride are replaced by a carboxylic drug. Lipid conjugates exhibit some physico-chemical and absorption characteristics similar to those of natural lipids. Non-steroidal, anti-inflammatory drugs such as acetylsalicylic acid, indomethacin, naproxen and ibuprofen were linked covalently to glycerides to reduce their ulcerogenicity. Mimicking the absorption process of dietary fats, lipid conjugates have also been used to target the lymphatic route (e.g., L-Dopa, melphalan, chlorambucil and GABA). Based on their lipophilicity and resemblance to lipids in biological membranes, lipid conjugates of phenytoin were prepared to increase intestinal absorption, whereas glycerides or modified glycerides of L-Dopa, glycine, GABA, thiorphan and N-benzyloxycarbonylglycine were designed to promote brain penetration. In phospholipid conjugates, antiviral and antineoplasic nucleosides were attached to the phosphate moiety. After presenting the biochemical pathways of lipids, the review discusses the advantages and drawbacks of lipidic prodrugs, keeping in mind the potential pharmacological activity of the fatty acid itself.
Platre MP, Jaillais Y. Anionic lipids and the maintenance of membrane electrostatics in eukaryotes. Plant Signal Behav. 2017 Feb;12(2):e1282022. doi: 10.1080/15592324.2017.1282022.
Abstract. A wide range of signaling processes occurs at the cell surface through the reversible association of proteins from the cytosol to the plasma membrane. Some low abundant lipids are enriched at the membrane of specific compartments and thereby contribute to the identity of cell organelles by acting as biochemical landmarks. Lipids also influence membrane biophysical properties, which emerge as an important feature in specifying cellular territories. Such parameters are crucial for signal transduction and include lipid packing, membrane curvature and electrostatics. In particular, membrane electrostatics specifies the identity of the plasma membrane inner leaflet. Membrane surface charges are carried by anionic phospholipids, however the exact nature of the lipid(s) that powers the plasma membrane electrostatic field varies among eukaryotes and has been hotly debated during the last decade. Herein, we discuss the role of anionic lipids in setting up plasma membrane electrostatics and we compare similarities and differences that were found in different eukaryotic cells.
Cascio M. Connexins and their environment: effects of lipids composition on ion channels. Biochim Biophys Acta. 2005 Jun 10;1711(2):142-53. doi: 10.1016/j.bbamem.2004.12.001.
Abstract. Intercellular communication is mediated through paired connexons that form an aqueous pore between two adjacent cells. These membrane proteins reside in the plasma membrane of their respective cells and their activity is modulated by the composition of the lipid bilayer. The effects of the bilayer on connexon structure and function may be direct or indirect, and may arise from specific binding events or the physicochemical properties of the bilayer. While the effects of the bilayer and its constituent lipids on gap junction activity have been described in the literature, the underlying mechanisms of the interaction of connexin with its lipidic microenvironment are not as well characterized. Given that the information regarding connexons is limited, in this review, the specific roles of lipids and the properties of the bilayer on membrane protein structure and function are described for other ion channels as well as for connexons.
Sakamaki JI, Mizushima N. Cell biology of protein-lipid conjugation. Cell Struct Funct. 2023 May 11;48(1):99-112. doi: 10.1247/csf.23016. Epub 2023 Apr 6. PMID: 37019684; PMCID: PMC10721952.
Abstract. Protein-lipid conjugation is a widespread modification involved in many biological processes. Various lipids, including fatty acids, isoprenoids, sterols, glycosylphosphatidylinositol, sphingolipids, and phospholipids, are covalently linked with proteins. These modifications direct proteins to intracellular membranes through the hydrophobic nature of lipids. Some of these membrane-binding processes are reversible through delipidation or by reducing the affinity to membranes. Many signaling molecules undergo lipid modification, and their membrane binding is important for proper signal transduction. The conjugation of proteins to lipids also influences the dynamics and function of organellar membranes. Dysregulation of lipidation has been associated with diseases such as neurodegenerative diseases. In this review, we first provide an overview of diverse forms of protein-lipid conjugation and then summarize the catalytic mechanisms, regulation, and roles of these modifications.Key words: lipid, lipidation, membrane, organelle, protein modification.
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