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Biosynthesis and Genetics of Lipopolysaccharide Core
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
David E. Heinrichs, Chris Whitfield, Miguel A. Valvano
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.
Features of Lipid Metabolism in Diabetes Mellitus and Ischemic Heart Disease
Published in E.I. Sokolov, Obesity and Diabetes Mellitus, 2020
Phosphatidylcholine (PC) and phosphatidylethanolamine (PEA) together with cholesterol are the main structural components of a cell membrane. We attach great significance to the ratio PEA/PC for appraising the structural and functional state inside a membrane.
Atherosclerosis
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
The synthesis of phospholipids is also enhanced in arteries with lesions as compared to normal arteries.421 The composition of phospholipids changes as atherosclerotic lesions evolve. The relative roles of deposition and synthesis of phospholipids in the accumulation are uncertain, but there is evidence that local synthesis of phospholipids plays a greater role than the deposition from the plasma.709 The rate of arterial wall phospholipid synthesis is greater in cholesterol-fed animals.685 Among individual phospholipids, the greatest absolute rise occurs in lecithin, but in relative terms sphingomyelin accumulation in the arterial lesions also increases significantly. Whenever lysolecithin concentration is raised several fold, phosphatidylethanolamine content shows no change.498 Furthermore, the sphingomyelin level is enhanced during the early stages of development although lecithin concentrations are elevated only after the lesions have reached an advanced phase. The sphingomyelin content of the arteries rises with age, and this accumulation of sphingomyelin is probably due to slow degradation of β-lipoproteins which are rich in this component. Removal of phospholipids from the arteries is also reduced. This may be connected with changes in the activity of various phospholipid hydrolases, particularly sphingomyelin phosphocholine hydrolase, which decreases with age.
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.
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).
MICROBIOTA INSIGHTS IN CLOSTRIDIUM DIFFICILE INFECTION AND INFLAMMATORY BOWEL DISEASE
Published in Gut Microbes, 2020
C. Rodríguez, E. Romero, L. Garrido-Sanchez, G. Alcaín-Martínez, RJ. Andrade, B. Taminiau, G. Daube, E. García-Fuentes
The impairment of intestinal barrier function or disruption of mucosal T cells by inflammatory mediators favor C. difficile colonization and toxin production. Some phospholipids, such as phosphatidylcholine and phosphatidylethanolamine, are released during this disruption. Phosphatidylcholine is converted into ethanolamine and glycerol by bacterial phosphodiesterases. C. difficile benefits from the breakdown of ethanolamine and utilizes it as a source of nitrogen and carbon.95,96 On the other hand, a higher glycosidase activity has been reported in IBD patients than in healthy subjects. Indeed, disruption of intestinal barrier function and the intestinal microbiota also entails the liberation of monosaccharides, which promote the multiplication and colonization of C. difficile.96 A previous study described in depth how C. difficile catabolises microbiota-liberated mucosal carbohydrates and how pathogen expansion is even aided by microbiota-induced elevation of sialic acid levels in vivo.97