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Lipids are a broad group of organic compounds which include fats,waxes,sterols,fat-soluble vitamins,monoglycerides,diglycerides,phospholipids,and others. The functions of lipids include storing energy,signaling,and acting as structural components of cell membranes. Lipids have applications in the cosmetic and food industries,and in nanotechnology.
Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids,joined by an alcohol residue. Marine phospholipids typically have omega-3 fatty acids EPA and DHA integrated as part of the phospholipid molecule. The phosphate group can be modified with simple organic molecules such as choline,ethanolamine or serine.
The stratum corneum is the outermost layer of the epidermis. Consisting of dead tissue,it protects underlying tissue from infection,dehydration,chemicals and mechanical stress. It is composed of 15–20 layers of flattened cells with no nuclei and cell organelles.
Lipidomics is the large-scale study of pathways and networks of cellular lipids in biological systems. The word "lipidome" is used to describe the complete lipid profile within a cell,tissue,organism,or ecosystem and is a subset of the "metabolome" which also includes other major classes of biological molecules. Lipidomics is a relatively recent research field that has been driven by rapid advances in technologies such as mass spectrometry (MS),nuclear magnetic resonance (NMR) spectroscopy,fluorescence spectroscopy,dual polarisation interferometry and computational methods,coupled with the recognition of the role of lipids in many metabolic diseases such as obesity,atherosclerosis,stroke,hypertension and diabetes. This rapidly expanding field complements the huge progress made in genomics and proteomics,all of which constitute the family of systems biology.
The plasma membranes of cells contain combinations of glycosphingolipids,cholesterol and protein receptors organised in glycolipoprotein lipid microdomains termed lipid rafts. Their existence in cellular membranes remains controversial. Indeed,Kervin and Overduin imply that lipid rafts are misconstrued protein islands,which they propose form through a proteolipid code. Nonetheless,it has been proposed that they are specialized membrane microdomains which compartmentalize cellular processes by serving as organising centers for the assembly of signaling molecules,allowing a closer interaction of protein receptors and their effectors to promote kinetically favorable interactions necessary for the signal transduction. Lipid rafts influence membrane fluidity and membrane protein trafficking,thereby regulating neurotransmission and receptor trafficking. Lipid rafts are more ordered and tightly packed than the surrounding bilayer,but float freely within the membrane bilayer. Although more common in the cell membrane,lipid rafts have also been reported in other parts of the cell,such as the Golgi apparatus and lysosomes.
Metabolomics is the scientific study of chemical processes involving metabolites,the small molecule substrates,intermediates,and products of cell metabolism. Specifically,metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind",the study of their small-molecule metabolite profiles. The metabolome represents the complete set of metabolites in a biological cell,tissue,organ,or organism,which are the end products of cellular processes. Messenger RNA (mRNA),gene expression data,and proteomic analyses reveal the set of gene products being produced in the cell,data that represents one aspect of cellular function. Conversely,metabolic profiling can give an instantaneous snapshot of the physiology of that cell,and thus,metabolomics provides a direct "functional readout of the physiological state" of an organism. There are indeed quantifiable correlations between the metabolome and the other cellular ensembles,which can be used to predict metabolite abundances in biological samples from,for example mRNA abundances. One of the ultimate challenges of systems biology is to integrate metabolomics with all other -omics information to provide a better understanding of cellular biology.
Sphingolipids are a class of lipids containing a backbone of sphingoid bases,which are 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 a terminal hydroxyl group is a ceramide. Other common groups bonded to the terminal oxygen atom include phosphocholine,yielding a sphingomyelin,and various sugar monomers or dimers,yielding cerebrosides and globosides,respectively. Cerebrosides and globosides are collectively known as glycosphingolipids.
Sphingomyelin is a type of sphingolipid found in animal cell membranes,especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphocholine and ceramide,or a phosphoethanolamine head group;therefore,sphingomyelins can also be classified as sphingophospholipids. In humans,SPH represents ~85% of all sphingolipids,and typically make up 10–20 mol % of plasma membrane lipids.
Fumonisin B1 is the most prevalent member of a family of toxins,known as fumonisins,produced by multiple species of Fusarium molds,such as Fusarium verticillioides,which occur mainly in maize (corn),wheat and other cereals. Fumonisin B1 contamination of maize has been reported worldwide at mg/kg levels. Human exposure occurs at levels of micrograms to milligrams per day and is greatest in regions where maize products are the dietary staple.
Ceramides are a family of waxy lipid molecules. A ceramide is composed of sphingosine and a fatty acid joined by an amide bond. 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 cell 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.
The lipidome refers to the totality of lipids in cells. Lipids are one of the four major molecular components of biological organisms,along with proteins,sugars and nucleic acids. Lipidome is a term coined in the context of omics in modern biology,within the field of lipidomics. It can be studied using mass spectrometry and bioinformatics as well as traditional lab-based methods. The lipidome of a cell can be subdivided into the membrane-lipidome and mediator-lipidome.
Sphingosine-1-phosphate (S1P) is a signaling sphingolipid,also known as lysosphingolipid. It is also referred to as a bioactive lipid mediator. Sphingolipids at large form a class of lipids characterized by a particular aliphatic aminoalcohol,which is sphingosine.
Serine palmitoyltransferase,long chain base subunit 1,also known as SPTLC1,is a protein which in humans is encoded by the SPTLC1 gene.
Serine palmitoyltransferase,long chain base subunit 2,also known as SPTLC2,is a protein which in humans is encoded by the SPTLC2 gene. SPTLC2 belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.
The Lactosylceramides,also known as LacCer,are a class of glycosphingolipids composed of a variable hydrophobic ceramide lipid and a hydrophilic sugar moiety. Lactosylceramides are found in microdomains on the plasma layers of numerous cells. Moreover,they are a type of ceramide including lactose,which is an example of a globoside.
Lysophosphatidylcholines,also called lysolecithins,are a class of chemical compounds which are derived from phosphatidylcholines.
1-Lysophosphatidylcholines are a class of phospholipids that are intermediates in the metabolism of lipids. They result from the hydrolysis of an acyl group from the sn-1 position of phosphatidylcholine. They are also called 2-acyl-sn-glycero-3-phosphocholines. The synthesis of phosphatidylcholines with specific fatty acids occurs through the synthesis of 1-lysoPC. The formation of various other lipids generates 1-lysoPC as a by-product.
Ceramide synthase 3 (CersS3),also known as longevity assurance homologue 3,is an enzyme that is encoded in humans by the CERS3 gene.
The 1-deoxysphingolipids (1-deoxySLs) are an atypical and recently discovered class of sphingolipids (SLs). They are formed during the nove synthesis pathway and their essential C1-OH deficit causes the malfunctions of the following transformations to achieve complex sphingolipids. In general,sphingolipids are formed during a reaction that is catalyzed by the SPT enzyme (serine-palmitoyltransferase) where the condensation of serine and palmitoyl-CoA takes place. The origin of this rare sphingolipid,though,is due to a defect of the SPT which can also use alanine or glycine. This change is what forms the 1-deoxySL.
References
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- 1 2 "Google Scholar–Markus R Wenk".
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- ↑ "NUS–Visiting Faculty".
- ↑ "SLING–Visiting Members".
- ↑ "New Head of Department of Biochemistry, NUS Medicine".
- ↑ Wenk, Markus R. (2005). "The emerging field of lipidomics". Nature Reviews Drug Discovery. 4 (7): 594–610. doi:10.1038/nrd1776. PMID 16052242.
- ↑ Wenk, Markus R.; Lucast, Louise; Di Paolo, Gilbert; Romanelli, Anthony J.; Suchy, Sharon F.; Nussbaum, Robert L.; Cline, Gary W.; Shulman, Gerald I.; McMurray, Walter; De Camilli, Pietro (2003). "Phosphoinositide profiling in complex lipid mixtures using electrospray ionization mass spectrometry". Nature Biotechnology. 21 (7): 813–817. doi:10.1038/nbt837. PMID 12808461.
- ↑ Guan, Xue Li; Wenk, Markus R. (2006). "Mass spectrometry-based profiling of phospholipids and sphingolipids in extracts from Saccharomyces cerevisiae". Yeast. 23 (6): 465–477. doi:10.1002/yea.1362. PMID 16652392.
- ↑ Chew, Wee Siong; Torta, Federico; Ji, Shanshan; Choi, Hyungwon; Begum, Husna; Sim, Xueling; Khoo, Chin Meng; Khoo, Eric Yin Hao; Ong, Wei-Yi; Van Dam, Rob M.; Wenk, Markus R.; Tai, E. Shyong; Herr, Deron R. (2019). "Large-scale lipidomics identifies associations between plasma sphingolipids and T2DM incidence". JCI Insight. 4 (13). doi:10.1172/jci.insight.126925. PMC 6629294 . PMID 31162145.
- ↑ Chua, Eric Chern-Pin; Shui, Guanghou; Lee, Ivan Tian-Guang; Lau, Pauline; Tan, Luuan-Chin; Yeo, Sing-Chen; Lam, Buu Duyen; Bulchand, Sarada; Summers, Scott A.; Puvanendran, Kathiravelu; Rozen, Steven G.; Wenk, Markus R.; Gooley, Joshua J. (2013). "Extensive diversity in circadian regulation of plasma lipids and evidence for different circadian metabolic phenotypes in humans". Proceedings of the National Academy of Sciences. 110 (35): 14468–14473. doi: 10.1073/pnas.1222647110 . PMC 3761633 . PMID 23946426.
- ↑ Nguyen, Long N.; Ma, Dongliang; Shui, Guanghou; Wong, Peiyan; Cazenave-Gassiot, Amaury; Zhang, Xiaodong; Wenk, Markus R.; Goh, Eyleen L. K.; Silver, David L. (2014). "Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid". Nature. 509 (7501): 503–506. doi:10.1038/nature13241. PMID 24828044.
- ↑ Vu, Thiet M.; Ishizu, Ayako-Nakamura; Foo, Juat Chin; Toh, Xiu Ru; Zhang, Fangyu; Whee, Ding Ming; Torta, Federico; Cazenave-Gassiot, Amaury; Matsumura, Takayoshi; Kim, Sangho; Toh, Sue-Anne E. S.; Suda, Toshio; Silver, David L.; Wenk, Markus R.; Nguyen, Long N. (2017). "Mfsd2b is essential for the sphingosine-1-phosphate export in erythrocytes and platelets". Nature. 550 (7677): 524–528. doi:10.1038/nature24053. PMID 29045386.
- ↑ "ASBMB Today–Harmonizing lipidomics".
- ↑ Burla, Bo; Arita, Makoto; Arita, Masanori; Bendt, Anne K.; Cazenave-Gassiot, Amaury; Dennis, Edward A.; Ekroos, Kim; Han, Xianlin; Ikeda, Kazutaka; Liebisch, Gerhard; Lin, Michelle K.; Loh, Tze Ping; Meikle, Peter J.; Orešič, Matej; Quehenberger, Oswald; Shevchenko, Andrej; Torta, Federico; Wakelam, Michael J.O.; Wheelock, Craig E.; Wenk, Markus R. (2018). "MS-based lipidomics of human blood plasma: a community-initiated position paper to develop accepted guidelines". Journal of Lipid Research. 59 (10): 2001–2017. doi: 10.1194/jlr.S087163 . PMC 6168311 . PMID 30115755.
- ↑ Liebisch, Gerhard; Ahrends, Robert; Arita, Makoto; Arita, Masanori; Bowden, John A.; Ejsing, Christer S.; Griffiths, William J.; Holčapek, Michal; Köfeler, Harald; Mitchell, Todd W.; Wenk, Markus R.; Ekroos, Kim (2019). "Lipidomics needs more standardization". Nature Metabolism. 1 (8): 745–747. doi:10.1038/s42255-019-0094-z. PMID 32694765.
- ↑ Triebl, Alexander; Wenk, Markus R. (2018). "Analytical Considerations of Stable Isotope Labelling in Lipidomics". Biomolecules. 8 (4): 151. doi: 10.3390/biom8040151 . PMC 6315579 . PMID 30453585.
- ↑ "iLS Reference materials and biological reference ranges".
- ↑ Torta, Federico; et al. (2024). "Concordant inter-laboratory derived concentrations of ceramides in human plasma reference materials via authentic standards". Nature Communications. 15 (1): 8562. doi:10.1038/s41467-024-52087-x. PMC 11449902 . PMID 39362843.
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