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Sphingolipids are a class of lipids containing a backbone of sphingoid bases, a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological sphinx because of their enigmatic nature. These compounds play important roles in signal transduction and cell recognition. Sphingolipidoses, or disorders of sphingolipid metabolism, have particular impact on neural tissue. A sphingolipid with an R group consisting of a hydrogen atom only is a ceramide. Other common R groups include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids.
Ceramides are a family of waxy lipid molecules. A ceramide is composed of N-acetylsphingosine and a fatty acid. Ceramides are found in high concentrations within the cell membrane of eukaryotic cells, since they are component lipids that make up sphingomyelin, one of the major lipids in the lipid bilayer. Contrary to previous assumptions that ceramides and other sphingolipids found in cell membrane were purely supporting structural elements, ceramide can participate in a variety of cellular signaling: examples include regulating differentiation, proliferation, and programmed cell death (PCD) of cells.
Lipid signaling, broadly defined, refers to any biological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses. Lipid signaling is thought to be qualitatively different from other classical signaling paradigms because lipids can freely diffuse through membranes. One consequence of this is that lipid messengers cannot be stored in vesicles prior to release and so are often biosynthesized "on demand" at their intended site of action. As such, many lipid signaling molecules cannot circulate freely in solution but, rather, exist bound to special carrier proteins in serum.
In enzymology, sphingosine N-acyltransferases (ceramide synthases (CerS), EC 2.3.1.24) are enzymes that catalyze the chemical reaction of synthesis of ceramide:
In enzymology, a ceramide kinase, also abbreviated as CERK, is an enzyme that catalyzes the chemical reaction:
In enzymology, a sphingomyelin synthase is an enzyme that catalyzes the chemical reaction
5'-AMP-activated protein kinase catalytic subunit alpha-1 is an enzyme that in humans is encoded by the PRKAA1 gene.
Transformer-2 protein homolog beta, also known as TRA2B previously known as splicing factor, arginine/serine-rich 10 (SFRS10), is a protein that in humans is encoded by the TRA2B gene.
Alpha-N-acetylneuraminide alpha-2,8-sialyltransferase is an enzyme that in humans is encoded by the ST8SIA1 gene.
Hyaluronan synthase 1 is an enzyme that in humans is encoded by the HAS1 gene.
Ceramide glucosyltransferase is an enzyme that in humans is encoded by the UGCG gene.
Hyaluronan synthase 3 is an enzyme that in humans is encoded by the HAS3 gene.
Neutral ceramidase is an enzyme that in humans is encoded by the ASAH2 gene.
Gopal Chandra Kundu is an renowned Indian cell and cancer biologist and a Senior Scientist (Scientist-G) at National Centre for Cell Science. He is known for his contributions towards the understanding the mechanism of cancer progression in breast, melanoma and other cancers and development of novel therapeutic targets and target-based therapy in cancers.
Very-long-chain 3-oxoacyl-CoA synthase (EC 2.3.1.199, very-long-chain 3-ketoacyl-CoA synthase, very-long-chain beta-ketoacyl-CoA synthase, condensing enzyme, CUT1 (gene), CERS6 (gene), FAE1 (gene), KCS (gene), ELO (gene)) is an enzyme with systematic name malonyl-CoA:very-long-chain acyl-CoA malonyltransferase (decarboxylating and thioester-hydrolysing). This enzyme catalyses the following chemical reaction
In enzymology, a ceramide phosphoethanolamine synthase is an enzyme that catalyzes the chemical reaction
Ceramide synthase 1 also known as LAG1 longevity assurance homolog 1 is an enzyme that in humans is encoded by the CERS1 gene.
Ceramide synthase 2, also known as LAG1 longevity assurance homolog 2 or Tumor metastasis-suppressor gene 1 protein is an enzyme that in humans is encoded by the CERS2 gene.
Ceramide synthase 3 (CersS3), also known as longevity assurance homologue 3, is an enzyme that is encoded in humans by the CERS3 gene.
Ceramide synthase 4 (CerS4) is an enzyme that in humans is encoded by the CERS4 gene and is one of the least studied of the ceramide synthases.
References
- ↑ Sujoy Lahiri; Anthony H Futerman (2005). "LASS5 is a bona fide dihydroceramide synthase that selectively utilizes palmitoyl-CoA as acyl donor". J Biol Chem. 280 (40): 33735–8. doi: 10.1074/jbc.m506485200 . PMID 16100120.
- ↑ Levy M, Futerman AH (2010). "Mammalian ceramide synthases". IUBMB Life. 62 (5): 347–56. doi:10.1002/iub.319. PMC 2858252 . PMID 20222015.
- ↑ Jin J, Hou Q, Mullen TD, Zeidan YH, Bielawski J, Kraveka JM, et al. (2008). "Ceramide generated by sphingomyelin hydrolysis and the salvage pathway is involved in hypoxia/reoxygenation-induced Bax redistribution to mitochondria in NT-2 cells". J Biol Chem. 283 (39): 26509–17. doi: 10.1074/jbc.M801597200 . PMC 2546549 . PMID 18676372.
- ↑ Riebeling C, Allegood JC, Wang E, Merrill AH, Futerman AH (Oct 2003). "Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors". J Biol Chem. 278 (44): 43452–9. doi: 10.1074/jbc.M307104200 . PMID 12912983.
- ↑ Xu Z, Zhou J, McCoy DM, Mallampalli RK (2005). "LASS5 is the predominant ceramide synthase isoform involved in de novo sphingolipid synthesis in lung epithelia". J Lipid Res. 46 (6): 1229–38. doi: 10.1194/jlr.M500001-JLR200 . PMID 15772421.
- ↑ Becker I, Wang-Eckhardt L, Yaghootfam A, Gieselmann V, Eckhardt M (2008). "Differential expression of (dihydro)ceramide synthases in mouse brain: oligodendrocyte-specific expression of CerS2/Lass2". Histochem Cell Biol. 129 (2): 233–41. doi:10.1007/s00418-007-0344-0. PMID 17901973. S2CID 2595275.
- ↑ Min J, Mesika A, Sivaguru M, Van Veldhoven PP, Alexander H, Futerman AH, et al. (2007). "(Dihydro)ceramide synthase 1 regulated sensitivity to cisplatin is associated with the activation of p38 mitogen-activated protein kinase and is abrogated by sphingosine kinase 1". Mol Cancer Res. 5 (8): 801–12. doi: 10.1158/1541-7786.MCR-07-0100 . PMID 17699106.
- ↑ van Hall T, Wolpert EZ, van Veelen P, Laban S, van der Veer M, Roseboom M, et al. (2006). "Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants". Nat Med. 12 (4): 417–24. doi:10.1038/nm1381. PMID 16550190. S2CID 33797315.
- ↑ Panjarian S, Kozhaya L, Arayssi S, Yehia M, Bielawski J, Bielawska A, et al. (2008). "De novo N-palmitoylsphingosine synthesis is the major biochemical mechanism of ceramide accumulation following p53 up-regulation". Prostaglandins Other Lipid Mediat. 86 (1–4): 41–8. doi:10.1016/j.prostaglandins.2008.02.004. PMID 18400537.