What disease is associated with metabolic disorders of sphingolipids?
Introduction. Many experimental and clinical studies have described the role of sphingolipids in the pathogenesis of lifestyle diseases such as myocardial infarction, hypertension, stroke and diabetes mellitus. They are involved in the regulation of numerous cellular processes, including apoptosis [1].
What is sphingolipid metabolism?
Sphingolipid metabolic pathway is an important cellular pathway that represents a highly coordinated system linking together various pathways, where ceramide occupies a central position in both biosynthesis and catabolism, thereby crafting a metabolic hub [9.
How are sphingolipids degraded?
Sphingolipid degradation occurs in the lysosome and depends upon two families of proteins: glycosyl hydrolases, and lipid-transfer proteins including saposins and the GM2 activator protein4,5,6,7. The hydrolases are water soluble while the substrates are embedded in lysosomal intraluminal vesicle membranes.
What is the disease condition of sphingolipid storage disease?
Sphingolipid storage diseases are caused by defective catabolic activities in the endolysosomal system of the cells. Lysosomal accumulation occurs predominantly in cells and organs that have the highest rates of biosynthesis or uptake of the undegradeable sphingolipids and their precursors.
What are two major types of sphingolipids?
Among the most simple sphingolipids are the ceramides (sphingosine plus a fatty acid), widely distributed in small amounts in plant and animal tissues. The other sphingolipids are derivatives of ceramides.
Where does sphingolipid synthesis occur?
Sphingolipids are synthesized in a pathway that begins in the ER and is completed in the Golgi apparatus, but these lipids are enriched in the plasma membrane and in endosomes, where they perform many of their functions.
Where are sphingolipids broken down?
Breakdown of sphingomyelin occurs through the hydrolysis of the phosphocholine headgroups by the sphingomyelinase family. The direct result of sphingomyelin hydrolysis is the production of ceramide and free phosphocholine.
Where are sphingolipids commonly found?
Sphingolipids are synthesized in a pathway that begins in the ER and is completed in the Golgi apparatus, but these lipids are enriched in the plasma membrane and in endosomes, where they perform many of their functions. Transport occurs via vesicles and monomeric transport in the cytosol.
How is lipid storage disease diagnosed?
Diagnosis of the lipid storage disorders can be achieved through the use of several tests. These tests include clinical examination, biopsy, genetic testing, molecular analysis of cells or tissues, and enzyme assays.
What are some examples of sphingolipids?
Sphingolipids attached to a glycan (or a carbohydrate) is referred to as glycosphingolipid. Examples are cerebrosides and gangliosides. Cerebrosides are glycosphingolipids found in the cell membranes of the neurons and the muscle cells. The cerebroside has a sphingosine core.
What is an example of sphingolipids?
What causes Wilson’s syndrome?
What causes Wilson disease? Mutations link of a gene called ATP7B cause Wilson disease. These gene mutations prevent the body from removing extra copper. Normally, the liver releases extra copper into bile.
What is the most common lipid storage disease?
What are the types of lipid storage disease?
- Type 1 (or nonneuronopathic type) is the most common form of the disease in the U.S. and Europe.
- Type 2 (or acute infantile neuropathic Gaucher disease) typically begins within 3 months of birth.
What are the disease condition of sphingolipid storage disease?
Lipid Storage Disorders/Sphingolipidoses Sphingolipidoses are lysosomal storage disorders in which enzymes of sphingolipid catabolism are absent. In these disorders, the sites of sphingolipid catabolism like lysosomes of phagocytes, histiocytes or macrophages in bone marrow, liver and spleen are affected.
What is Maroteaux Lamy Syndrome?
Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI; MPS VI) is a rare genetic disorder characterized by complete or partial lack of activity of the enzyme arylsulfatase B (also called N-acetylgalactosamine-4-sulfatase), encoded by the ARSB gene.
Do sphingolipids play a role in cancer drug resistance?
Drug resistance continues to be one of the major challenges to cure cancer. As research in this field evolves, it has been proposed that numerous bioactive molecules might be involved in the resistance of cancer cells to certain chemotherapeutics. One well-known group of lipids that play a major role in drug resistance are the sphingolipids.
How does sphingolipid metabolism promote MOMP?
NSMase-dependent sphingolipid metabolism promoted MOMP via coordinated activation of BAX and BAK, suggesting that BCL-2 homology 3 (BH3)-only proteins and the specific sphingolipid milieu at the mitochondrial membrane regulate apoptosis 88.
What is the role of Sphingolipid metabolites in inflammatory disease?
Maceyka, M. & Spiegel, S. Sphingolipid metabolites in inflammatory disease. Nature 510, 58–67 (2014). Huang, W. C. et al. Sphingosine-1-phosphate phosphatase 2 promotes disruption of mucosal integrity, and contributes to ulcerative colitis in mice and humans. FASEB J. 30, 2945–2958 (2016).
What are the enzymes involved in sphingolipid metabolism?
Figure 1: Pathways of sphingolipid metabolism and key enzymes. Ceramide is the central molecule in sphingolipid metabolism and can be synthesized de novo (dark blue boxes) by the functions of serine palmitoyltransferase (SPT), 3-ketosphinganine reductase, (dihydro)ceramide synthases (CERS1–6) and dihydroceramide desaturase (DES).