A distinctive property of sphingolipids in membranes is that they spontaneously form transient nanodomains termed ' rafts ', usually in conjunction with cholesterol, where such proteins as enzymes and receptors congregate to carry out their signalling and other functions.
Thus, in addition to their direct effects on metabolism, sphingolipids affect innumerable aspects of biochemistry indirectly via their physical properties. While it may be obvious that a well-balanced sphingolipid metabolism is important for health in animals, increasing evidence has been acquired to demonstrate that impaired sphingolipid metabolism and function are involved in the pathophysiology of many of the more common human diseases.
These include diabetes, various cancers, microbial infections, Alzheimer's disease and other neurological syndromes, and diseases of the cardiovascular and respiratory systems. A number of genetic defects in sphingolipid metabolism or sphingolipidoses, especially lysosomal storage diseases, are also important in humans.
Sphingolipids and their metabolism are therefore likely to prove of ever increasing interest to scientists. There are appreciable differences in sphingolipid compositions and metabolism between animal and plant cells, both with respect to the aliphatic components and especially the polar head groups, although there are also some important similarities.
While sphingomyelin is the most abundant sphingolipid in animals, it does not occur in plants and fungi. Although less is known of the role they play in plants, it has become apparent that complex sphingolipids are much more abundant in plant membranes than was once believed, and it is now recognized that they are key components of the plasma membrane and endomembrane system.
The biosynthesis and catabolism of sphingolipids involves a large number of intermediate metabolites, all of which have distinctive biological activities of their own. Many different enzymes and their isoforms are involved, and their activities depend on a number of factors, including intracellular locations and mechanisms of activation. Each of the various compounds in these pathways has characteristic metabolic properties, and these are discussed in more detail on the web pages describing the individual sphingolipids.
Thus, free sphingosine and other long-chain bases , which are the primary precursors of ceramides and thence of all the complex sphingolipids, function as mediators of many cellular events, for example by inhibiting the important enzyme protein kinase C.
Ceramides are involved in cellular signalling, and especially in the regulation of apoptosis, and cell differentiation, transformation and proliferation, and most stress conditions. Most of the reactions in the sphingomyelin cycle are reversible and the relevant enzymes are located in the endoplasmic reticulum, Golgi, plasma membrane and mitochondria, but the more complex sphingolipids are catabolized in the lysosomal compartment. Metabolic pathways that are comparable to those of the sphingomyelin cycle are believed to occur in plants, although they have not been studied as extensively as those in animals.
However, sphingolipid metabolites such as sphingosinephosphate or analogues have been linked to programmed cell death, signal transduction, membrane stability, host-pathogen interactions and stress responses, for example.
Plants also have a unique range of complex sphingolipids in their membranes, such as ceramide phosphorylinositol and the phytoglycosphingolipids , and these are now known to constitute a higher proportion of the total lipids than had hitherto been supposed, although their functions have hardly been explored.
While sphingolipids are produced by relatively few bacterial species, sulfono-analogues of long-chain bases and ceramides capnoids are produced by some species, but for convenience, these are discussed with the sulfonolipids. The fatty acids of sphingolipids are very different from those of glycerolipids, consisting of very-long-chain up to C 26 odd- and even-numbered saturated or monoenoic and related 2- R -hydroxy components, while even longer fatty acids C 28 to C 36 occur in spermatozoa and the epidermis.
The dienoic acid 15,tetracosadienoate n -6 , derived from elongation of linoleic acid, is found in the ceramides and other sphingolipids of a number of different tissues, but at relatively low levels. Polyunsaturated fatty acids are only rarely present, although sphingomyelins of testes and spermatozoa are exceptions in that they contain such fatty acids, which are even longer in chain-length up to 34 carbon atoms and include n -6 and n Skin ceramides also contain unusual very-long-chain fatty acids, while yeast sphingolipids are distinctive in containing mainly C 26 fatty acids.
In plants and yeasts, a similar range of chain-lengths occur as in animals, but 2-hydroxy acids predominate sometimes accompanied by small amounts of 2,3-dihydroxy acids; saturated fatty acids are most abundant, but monoenes are present in higher proportions in the Brassica family including Arabidopsis and a few other species.
Very-long-chain saturated and monoenoic fatty acids for sphingolipid biosynthesis are produced from medium-chain precursors by elongases ELOVL in the endoplasmic reticulum of cells in mammals, and there is increasing evidence that specific isoforms are involved in the biosynthesis of certain ceramides see our web page on long-chain bases.
Yeasts possess three elongation enzymes: Elo1 for medium to long-chain fatty acids , Elo2 up to C 22 and Elo3 up to C Hydroxylation is effected by a fatty acid 2-hydroxylase in mammals, i. The enantiomer mirror image isomer of L-glyceraldehyde is D-glyeraldehyde, in which the OH on C2 points to the right. Biochemists use L and D for lipid, sugar, and amino acid stereochemistry, instead of the R,S nomenclature you used in organic chemistry.
The stereochemical designation of all the sugars, amino acids, and glycerolipids can be determined from the absolute configuration of L- and D-glyceraldehyde. The first step in the in vivo in the body synthesis of chiral derivatives from the achiral glycerol involves the phosphorylation of the OH on C3 by ATP a phosphoanhydride similar in structure to acetic anhydride, an excellent acetylating agent to produce the chiral molecule glycerol phosphate.
Based on the absolute configuration of L-glyceraldehyde, and using this to draw glycerol with the OH on C2 pointing to the left , we can see that the phosphorylated molecule can be named L-glycerolphosphate. Hence biochemists have developed the stereospecific numbering system sn , which assigns the 1-position of a prochiral molecule to the group occupying the proS position.
Using this nomenclature, we can see that the chiral molecule described above, glycerol-phosphate, can be unambiguously named as sn-glycerolphosphate. The hydroxyl substituent on the proR carbon was phosphorylated. Figure 1: Phospholipids int he Cell Membrane. Furthermore, triglycerides are another type of lipid found in the cell. They are a form of fat stored in the fat cells. Triglycerides have three fatty acid molecules attached to the glycerol backbone.
Also, they help to maintain the structure of the cell membrane while serving as an energy source. Sphingolipids are the second most abundant form of lipids in the cell membrane.
They mainly occur in the cell membranes of nerve cells and brain cells. The backbone of sphingolipids is a sphingosine molecule. A sphingosine molecule consists of a three-carbon moiety, which contains two alcohol groups and an amino group.
The three-carbon moiety is then attached to a long hydrocarbon chain. Also, based on the side chains attached to the sphingosine molecule, there are two types of sphingolipids. Ceramide, derived from the agonist-induced hydrolysis of sphingomyelin, is a potent biomolecule with effects in multiple cell signaling pathways. The steroid hormone progesterone stimulated sphingomyelin hydrolysis in Xenopus oocytes.
Ceramide, derived from the "sphingomyelin cycle," was sufficient for meiotic cell cycle progression in the oocytes.
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