Diseases of the Nervous System
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
The profound damage in the central nervous system is associated with increased sphingomyelin, gangliosides, several ganglioside derivatives, and cholesterol in the grey matter. In the brain, sphingomyelin is not confined to the grey matter, but is also found in the white matter, although its turnover is more rapid in the grey matter. The major compounds accumulating in this condition are sphingomyelin, ceramide phosphorylcholine, and the metabolic defect is linked with the drastic reduction of sphingomyelinase enzyme which catalyzes the hydrolysis of sphingomyelin. The sphingomyelin stored in tissues of patients with Niemann-Pick disease originates in part from erythrocyte stroma, which contains high quantities, besides phosphatidylcholine and -ethanolamine. It is not surprising, therefore that the reticuloendothelial system, where erythrocytes are normally destroyed is one of the places ofsphingomyelin storage. Sphingomyelin is also the major lipid component of the plasma membrane of all cells and is an important constituent of subcellular organelles. Thus a large amount of sphingomyelin could continuously arise during the course of cellular turnover of a variety of tissues.319 There is no increase of sphingomyelin in the blood.
Macronutrients
Chuong Pham-Huy, Bruno Pham Huy in Food and Lifestyle in Health and Disease, 2022
Sphingolipids constitute a class of lipids defined by their 18 carbon-amino-alcohol backbones which are synthesized in the endoplasmic reticulum from non-sphingolipid precursors (66, 117). In sphingolipids, glycerol is replaced by a group of aliphatic amino alcohol named sphingosine that contains two alcohols with the middle position occupied by an amine. Sphingolipids are complex lipids which yield fatty acids, sphingosine, phosphoric acid, and an alcohol component upon hydrolysis. A sphingosine has three parts, a three carbon chain with two alcohols and amine attached and a long hydrocarbon chain containing 12–22 carbon atoms (69, 115, 117). The main and abundant component of sphingolipids in animals is sphingomyelin that constitutes the membranous myelin sheath surrounding nerve cell axons (114, 117). Sphingomyelin usually consists of a sphingosine linked to a long chain fatty acyl chain called ceramide and attached to a phosphocholine group at the primary alcohol group of a sphingosine (66, 117). Precisely, ceramide is amide of fatty acids with sphingosine. So, sphingomyelin can also be classified as sphingophospholipid (115). Like glycerophospholipids and cholesterol, sphingolipids are ubiquitous in the body and found in every cell membrane, particularly nerve cells and brain tissues (114–117).
Structures and Properties of Self-Assembled Phospholipids in Excess Water
E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson in Phospholipid-Binding Antibodies, 2020
Because of the identical phosphorylcholine headgroup, sphingomyelin appears structurally to resemble phosphatidylcholine. In fact, these two phospholipids are quite different in other aspects. As discussed above, sphingomyelin is a more asymmetrical molecule. In addition, the secondary hydroxyl and the amide bond in sphingomyelin can afford important intra- and intermolecular hydrogen bond capabilities. In fact, conformational analysis of sphingomyelin strongly suggests that the secondary hydroxyl group of the sphingosine base and the ester oxygen sandwiched in between the phosphorus atom and the C-l of the sphingosine base are intramolecularly hydrogen bonded.22 The number of atoms in the ring formed by closing the intramolecular H-bond is six (Figure 4). In the case of phosphatidylcholine, there is no H-bond donor within the molecule; hence, intramolecular hydrogen bond as well as direct intermolecular H-bond between PC molecules cannot occur.
Biological membranes in EV biogenesis, stability, uptake, and cargo transfer: an ISEV position paper arising from the ISEV membranes and EVs workshop
Published in Journal of Extracellular Vesicles, 2019
Ashley E. Russell, Alexandra Sneider, Kenneth W. Witwer, Paolo Bergese, Suvendra N. Bhattacharyya, Alexander Cocks, Emanuele Cocucci, Uta Erdbrügger, Juan M. Falcon-Perez, David W. Freeman, Thomas M. Gallagher, Shuaishuai Hu, Yiyao Huang, Steven M. Jay, Shin-ichi Kano, Gregory Lavieu, Aleksandra Leszczynska, Alicia M. Llorente, Quan Lu, Vasiliki Mahairaki, Dillon C. Muth, Nicole Noren Hooten, Matias Ostrowski, Ilaria Prada, Susmita Sahoo, Tine Hiorth Schøyen, Lifu Sheng, Deanna Tesch, Guillaume Van Niel, Roosmarijn E. Vandenbroucke, Frederik J. Verweij, Ana V. Villar, Marca Wauben, Ann M. Wehman, Hang Yin, David Raul Francisco Carter, Pieter Vader
Sphingomyelin is a sphingolipid normally found in the outer leaflet of membranes (extracellular or luminal side). Enzymes such as neutral sphingomyelinase (nSMase) and acid sphingomyelinase (aSMase) convert sphingomyelin into phosphocholine and ceramide, which alters membrane fluidity and promotes microdomain formation. Interestingly, 62% of survey respondents believe that lipid rafts/microdomains contribute to the formation of vesicles [69,70] (Figure 6). nSMase inhibitors, such as GW4869, have been shown to significantly reduce small EV release from some [71], but not all systems [72], and even results in a compensatory increase in large EVs in some systems [73]. Conversely, overexpressing nSMase2 increases ILV formation, which is thought to occur via an ESCRT-independent biogenesis pathway [71]. More than half (59%) of ISEV workshop participants doubted nSMase2 involvement in the biogenesis of all EV subtypes (Figure 6), but there is also evidence that aSMases are involved in EV release [74]. Thus, the roles of various sphingomyelinases, ceramide, and lipid rafts in EV biogenesis require further investigation.
Lipid–drug conjugates and associated carrier strategies for enhanced antiretroviral drug delivery
Published in Pharmaceutical Development and Technology, 2020
Funanani Takalani, Pradeep Kumar, Pierre P. D. Kondiah, Yahya E. Choonara, Viness Pillay
Phospholipids are lipid structures comprising of polar and non-polar potions as well as a phosphorous element. Owing to the presence of alcohol groups, phospholipids can be divided into glycerophospholipids and sphingomyelins (Li et al. 2014). Glycerophospholipids are the main phospholipids containing α-structure, L-configuration, and glycerol as the backbone. Chemical structures of glycerophospholipids and sphingomyelins are closely related except that in sphingomyelins, the backbone is a sphingosine. During conjugation, drugs can attach to the glycerol backbone at position sn-2 using an enzyme called phospholipase A2 (PLA2) or they can directly attach to the phosphate group by replacing the fatty acid either in positions sn-1 or sn-2 (Markovic et al. 2019). Conjugates developed from these strategies can improve incorporation of drugs into lipid-based delivery systems to enhance absorption and stability of the drug (Arouri and Mouritsen 2011). Phospholipids compounds possess anti-HIV-1 activity which works by altering viral envelopes and membrane cell surface (Krugner-Higby et al. 1995).
Roles of membrane lipids in the organization of epithelial cells: Old and new problems
Published in Tissue Barriers, 2018
Kai Simons and colleagues examined the compositional differences of membrane lipids in the apical and basolateral membranes by taking advantage of the enveloped virus. They extracted lipids from the fowl plague virus that selectively sprouts from the apical membrane and the vesicular somatitis virus that emerges from the basolateral membrane in MDCK cells and compared the lipid composition of these enveloped viruses. This pioneering work revealed that sphingomyelin is enriched, compared to phosphatidylcholine, in the apical membrane but not in the basolateral membrane.3 The fact that sphingolipid-rich domains exist in the apical membrane was later extended to the concept of “lipid raft”.4 Kai Simons and colleagues first described that sphingolipids biosynthesized in the Golgi apparatus form lipid rafts with cholesterol in the trans-Golgi network and then a group of proteins having affinity for lipid rafts such as GPI anchor proteins assemble to form transport vesicles directed to the apical membrane. In fact, GPI-anchored proteins often have saturated fatty acids in their lipid moiety and have affinity to detergent-insoluble fractions.5 Thus, lipid rafts were proposed as a mechanism of polar transport to the apical membranes in epithelial cells.6 In this way, the sphingolipids-enriched membrane domain is assumed to be involved in the establishment of apico-basal polarity.
Related Knowledge Centers
- Axon
- Ceramide
- Ethanolamine
- Fatty Acid
- Sphingolipid
- Sphingosine
- Cell Membrane
- Myelin
- Neuron
- Phosphocholine