Biosynthesis and Genetics of Lipopolysaccharide Core
Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison in Endotoxin in Health and Disease, 2020
The structures of the five outer core OS types from E. coli and the single structure from Salmonella are shown in Figure 5. Mutants blocked in the synthesis of specific sugar nucleotide precursors gave early indications of the sequence in outer core OS assembly. For example, in the absence of exogenous galactose in the growth medium, Salmonella mutants with a defect in the UDP-galactose-4-epimerase gene (galE) contain incomplete LPS lacking all sugars beyond the proximal glucose (Hexose I) (80,81). Mutants unable to synthesize UDP-glucose (e.g., pgi, galU) produce hexose-deficient LPS. The presence of glycosyltransferases that are capable of elongating the core OS in such mutants was subsequently demonstrated through assays for glycosyltransferase activity. These assays identify incorporation of radiolabeled sugars (from nucleotide sugar precursors) into mutant LPS acceptor in the presence of crude cell extracts and membranes. Of note, purified LPS is incapable of serving as an acceptor in combination with crude preparations of soluble glycosyltransferases (82). Membrane phospholipid, or phosphatidylethanolamine, is a requisite for enzymatic activity (5,82–86). Membrane reconstitution involving LPS, phospholipid, and glycosyltransferases was successfully used for the study of galactosyltransferase activity (86,87,149) and led to the tentative model for core OS assembly by Rothfield and coworkers (5). In the following sections we attempt to summarize the current status of biochemical and genetic data pertaining to outer core OS biosynthesis.
Emerging ergogenic aids for strength/power development
Jay R Hoffman in Dietary Supplementation in Sport and Exercise, 2019
Phosphatidylethanolamine (PE) is another phospholipid found in biological cell membranes most concentrated in the internal leaflet and is abundant in the mitochondria. It has similarities in structure to other phospholipids but has ethanolamine combined with its phosphate group (Figure 14.7). PE accounts for 20–30% of phospholipid pool (9). It is synthesized via decarboxylation of PS (by the actions of PS decarboxylase) and by the addition of cytidine diphosphate-ethanolamine to diglycerides. PE can also form PC via methylation from SAM. Some dietary sources of PE include beef, chicken, eggs, pork, soybeans, whole milk, peanuts, tuna, salmon and other fish (9, 14). Endurance athletes have been shown to have significantly higher PE content in skeletal muscle suggesting that chronic endurance training may up-regulate PE (45). Acute exercise appears to have no effect on muscle PE; however, significant reduction in muscle PE have been reported in endurance athletes two hours post exercise (45).
Phospholipids and the Clotting Process
E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson in Phospholipid-Binding Antibodies, 2020
In 1961, Bangham27 showed that membranes containing anionic dicetylphosphate express maximal coagulant activity at an optimal net negative surface charge. This observation was subsequently confirmed for phospholipid mixtures composed of phosphatidylserine with phosphatidylcholine or phosphatidylethanolamine.20,28 More recently, the same conclusions were reached on the basis of kinetic studies of coagulation factor activation in model systems. Both Pusey and Nelsestuen29 and van Rijn et al.23 have shown that the complete prothrom-binase complex (cf. Table 1) is maximally active at low mole percentages of phosphatidylserine, while in the absence of the nonenzymatic cofactor Va the membranes have to contain more phosphatidylserine in order to express maximal prothrombin-converting activity.23 It should be mentioned, however, that phosphatidylserine is exceptional among the negatively charged procoagulant phospholipids, in that it retains procoagulant activity even when the phospholipid surface has a net positive charge (vide infraSection VI).
MicroRNA-21-containing microvesicles from tubular epithelial cells promote cardiomyocyte hypertrophy
Published in Renal Failure, 2021
Jia Di, Min Yang, Hua Zhou, Min Li, Jiabi Zhao
In the present study, we first induced the injury of renal tubular epithelial cells with TGF-β1 and collected the conditioned medium. MVs were extracted and observed under electron microscope (Figure 1). MV is a microcosm of cell state. In general, cell membrane phospholipids, such as phosphatidylserine (PS) and phosphatidylethanolamine (PE), are located inside of the cell membrane. When the intracellular calcium concentration is increased, PS turns from the inside of the cell membrane to the outside [12]. In this study, donor cells were labeled with fluorescent dye Dil-C18, because Dil-C18 is a type of lipid dye, which can be used to label the cell membrane of donor cells. The lipid membrane structure of MV usually contains the cell membrane from donor cells. When donor cells secrete MVs, the MVs are also labeled with Dil-C18 [8]. Therefore, such labeling can be used to verify whether the MVs produced by donor cells can enter the recipient cells. In our present study, the recipient cardiomyocytes treated with MVs could be labeled with Dil-C18, and the longer of the treatment, the more MVs entered the cells. These results showed that MVs could be transmitted from tubular epithelial cells to cardiomyocytes (Figure 2).
Rationale utilization of phospholipid excipients: a distinctive tool for progressing state of the art in research of emerging drug carriers
Published in Journal of Liposome Research, 2023
Koilpillai Jebastin, Damodharan Narayanasamy
Soybeans, flaxseed, sunflower, wheat germ, egg yolk, milk, and canola seed, all contain natural phospholipids, such as phosphatidylcholine, phosphatidylglycerol, phosphatidylserine, phosphatidylethanolamine, etc. The raw material sources influence the phospholipid and fatty acid compositions of lecithins (Baer 1965, Pfennig 1996, Acevedo-Fani and Singh 2022). Soybean phospholipids are mostly used in oral and dermal pharmaceuticals. The skin is also treated with hydrogenated soybean phospholipids. According to the FDA's (Food and Drug Administration) Inactive Ingredient (excipient) list, both natural and synthesized phospholipids are frequently found in parenteral products. In contrast to synthetic phospholipids, which are frequently used in pharmaceutical formulations, Figure 4 shows acceptable natural phospholipid alternatives.
Improving cellular uptake of therapeutic entities through interaction with components of cell membrane
Published in Drug Delivery, 2019
Renshuai Zhang, Xiaofei Qin, Fandong Kong, Pengwei Chen, Guojun Pan
Phospholipid bilayer is the basic scaffold of cell membrane, which consist of a hydrophobic and a hydrophilic portion (van Meer et al., 2008). The hydrophobic moieties propend to self-associate (entropically driven by water), and the hydrophilic moieties tend to interact with aqueous environments, thus spontaneously form phospholipid bilayer. Membrane lipids contain three major structural lipids, glycerophospholipids, sphingolipids, and cholesterol, respectively. Glycerophospholipids primarily consists of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS) (Figure 1(A)). Sphingomyelin (SM) is the major sphingolipid in mammalian cells. Cholesterol is the major non-polar lipids of cell membranes. Except for cholesterol, the hydrophobic portions are diacylglycerol and ceramide, which contains saturated or unsaturated fatty acyl chains of varying lengths. The three major hydrophobic portions are highly associated with the cell uptake of lipophilic small molecules by simple diffusion. Because soluble in lipid bilayer is a prerequisite for small molecules penetrate into cells by simple diffusion. The hydrophilic portion consists of phosphate and nucleophilic amine (in PS and PE)/quaternary amine (in PC and SM), the former can interact with guanidine to form a bidentate bond and the latter can be captured by 2-acetylphenylboronic acid to form an iminoboronate (Figure 1(B)). The cellular uptake of a large of cargoes (including small molecules, macromolecules, and drug carriers) may be enhanced by interacting with phospholipid bilayer described as above.
Related Knowledge Centers
- Amine
- Cytidine Diphosphate
- Cytidine Monophosphate
- Diglyceride
- Ethanolamine
- Methylation
- Phosphatidylcholine
- Phospholipid
- Biological Membrane
- S-Adenosyl Methionine