Diseases of the Nervous System
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
In Gaucher’s disease, the neural changes are frequently severe, and the brain involvement shows marked but patchy loss of nerve cells and neuronophagia. Some neurons store glycolipid, and this substance accumulates also in the liver, spleen, bone marrow, lymph glands, and occasionally the brain, with Gaucher cells. The reticuloendothelial cells accumulate ceramide glucoside or glucocerebroside, and in the spleen it may increase from the normal 0.1 to 0.2% up to 4% in Gaucher’s disease.319 The affected neurons also contain cerebrosides. The metabolic defect comprises the deficiency of glucocerebrosidase which catalyzes the hydrolytic breakdown of glucocerebroside to glucose and N-acylsphingosine (Table 3). This enzyme is also present in normal human brain, and in Gaucher’s disease it is reduced to minimum levels or completely absent. The loss of this enzyme activity is the probable cause of the neuropathological manifestations. Gangliosides are the source of glucocerebroside in peripheral tissues of patients suffering from Gaucher’s disease and are likely the principal substances of glucocerebroside accumulating in the brain.85
Phosphonic Acids In Nature
Richard L. Hilderbrand in The Role of Phosphonates in Living Systems, 2018
The cerebrosides from the muscle of T. cornutus contain primarily N-methyl-AEP, with some AEP, and the cerebrosides from the viscera contain only the N-methyl-AEP derivative; the long-chain base and fatty acid composition is similar in the cerebrosides of both muscle and viscera.60,61 The visceral cerebrosides contain more hydroxylated fatty acids than do the muscle cerebrosides. A notable feature is that a molecular species of the cerebrosides from viscera contains normal (dihydroxy) long-chain bases and hydroxylated fatty acids. This does not occur in the ceramide-N-methyl-AEP and is a characteristic in common with galactosylceramide and may show a common biosynthetic pathway for the phosphonyl cerebroside and the galactosylceramide.61
Fungal Lipids
Rajendra Prasad, Mahmoud A. Ghannoum in Lipids of Pathogenic Fungi, 2017
Glycosyl ceramides with an attached sugar moiety are produced by a number of fungi and include cerebrosides and glycosphingolipids similar to those associated with the nervous system, e.g. the glucocerebroside in the dimorphic human pathogen S. schenkii.116 The carcinogenic effects of grain and other materials contaminated with the mycotoxic fungus F. moniliforme on mammals have been attributed to inhibition of sphingolipid biosynthesis by fumonisins, a family of compounds with structural similarities to the long-chain (sphingoid) bases of sphingolipids.117 The associated ccumulation of sphinganine suggested that fumonisins interfered with the conversion of [14C]-sphinganine to N-acyl-[14C]-sphinganine, a step that precedes introduction of the 4,5-trans double bond of sphingosine. It was postulated that disruption of the de novo pathway of sphingolipid synthesis may be a critical event in the diseases associated with the consumption of fumonisins.
New insights into human prefrontal cortex aging with a lipidomics approach
Published in Expert Review of Proteomics, 2021
Mariona Jové, Natalia Mota-Martorell, Pascual Torres, Manuel Portero-Otin, Isidre Ferrer, Reinald Pamplona
This specific lipid pattern present in hPFC is also projected at the cellular, subcellular, and molecular levels. Thus, for instance, at the cellular level, by using IMS (imaging mass spectrometry) [82,83] it is possible to obtain density maps for lipid species such as PC, PE, and SM that exhibit a different and specific distribution among the six different layers of the hPFC [82]. At the mitochondrial and microsomal levels, the three major phospholipid classes in hPFC are PC, PE, and PS [82]. PC cover about 55% of total phospholipids, with PC(16:0/16:0), PC(16:0/18:1), and PC(18:0/18:1) being the main molecular species. PEs represent about 30%, with PE(16:0/22:6), PE(18:0/20:4), PE(18:0/22:6), and PE(18:0/22:4) as the major molecular species. Finally, PSs represent 15%, with the main lipid species being PS(18:0/18:1) and PS(18:0/22:6). Other glycerophospholipids such as PI and cardiolipin were not evaluated. At the cell membrane level, a specific lipid profile is described in lipid rafts that are microdomains which offer a highly saturated liquid-ordered microenvironment that favors protein-lipid and protein–protein interaction, and which play an essential role in intercellular communication and signal transduction [83,84]. Lipid rafts from hPFC are characterized by a higher level of sphingolipids (cerebrosides, SM, and sulfatides) and cholesterol and lower concentration in GP (particularly aminophospholipids (PS and PE), and to a lesser degree PC and PI) compared to the non-raft membranes [85].
Synthesis and structure-activity relationships of cerebroside analogues as substrates of cerebroside sulphotransferase and discovery of a competitive inhibitor
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Wenjin Li, Joren Guillaume, Younis Baqi, Isabell Wachsmann, Volkmar Gieselmann, Serge Van Calenbergh, Christa E. Müller
Psychosine was purchased from Sigma (Steinheim, Germany). Galactosylceramide and glucosylceramide were obtained from Matreya LLC (Pleasant Gap, PA); according to the supplier, cerebroside consists of a mixture of saturated or unsaturated fatty acid residues (C16:0, C18:0, C20:0, C22:0, C23:0, C24:0–C27:0, C24:1–C27:1) or hydroxyacyl residues (C18:0(2–OH), C20:0(2–OH), C22:0(2–OH), C23:0(2–OH), C24:0(2–OH), C24:1(2–OH), C25:0(2–OH)) and glucosylceramide are a mixture of glucosylceramide with saturated or unsaturated fatty acid residues (C16:0, C18:0, C20:0, C22:0, C23:0, C24:0, C24:1). 3-Phosphoadenosine-5-phosphosulphate (PAPS) was purchased from Bellbrook Labs (No. 2059) in high purity. Other commercial sources of PAPS typically contain significant amounts of PAP and are, therefore, not suitable for the assay18. α-Galactosylceramide (KRN7000) was purchased from Avanti Polar Lipids, (Alabaster, AL). β-KRN7000 was synthesised and provided by the laboratory of S. van Calenbergh.
Ceramide pathway: A novel approach to cancer chemotherapy
Published in Egyptian Journal of Basic and Applied Sciences, 2018
Mahdi Mashhadi Akbar Boojar, Masoud Mashhadi Akbar Boojar, Sepide Golmohammad
Sphingolipids are a class of lipids with sphingosine as a complex amino alcohol core containing 18 carbons, which together with glycerolipids and sterols, form the major part of the cell membrane structure. Ceramide as ubiquitous sphingolipids is composed of a sphingosine, which is amide-bonded to a fatty acyl chain with different numbers of carbons, ranging from 14 to 26 [16]. Ceramides are one of the major components of the cell membrane and play a key role in protecting the cell from environmental stress [11]. The addition of phosphoethanolamine, monosaccharide or oligosaccharide together with sialic acid to ceramide leads to the formation of sphingomyelin, cerebrosides, and ganglioside, which, apart from the structural importance, they play a role as biological markers and the binding agent of extracellular ligands to the receptor [3,17] .
Related Knowledge Centers
- Ceramide
- Galactose
- Glucocerebroside
- Glucose
- Glycosphingolipid
- Muscle
- Polysaccharide
- Cell Membrane
- Neuron
- Galactosylceramide