The basic composition of complex sphingolipids includes a ceramide backbone and often a polar head group at position 1. Typically, sphingolipids are categorized based on their head group into two main classes: phosphosphingolipids (PSLs) and glycosphingolipids (GSLs); however, these groups are not mutually exclusive.
How are complex sphingolipids formed?
Complex sphingolipids may be formed by addition of head groups to ceramide or phytoceramide: Sphingomyelins have a phosphocholine or phosphoethanolamine molecule with an ester linkage to the 1-hydroxy group of a ceramide.
What is the difference between sphingolipids and glycolipids?
The other sphingolipids are derivatives of ceramides. Glycolipids, a large group of sphingolipids, are so called because they contain one or more molecules of sugar (glucose or galactose). Glycolipids, a general property of which is immunological activity, include the cerebrosides, gangliosides, and ceramide oligosaccharides.
What is the backbone of sphingolipid made of?
The sphingosine backbone is O-linked to a (usually) charged head group such as ethanolamine, serine, or choline. The backbone is also amide-linked to an acyl group, such as a fatty acid. Simple sphingolipids, which include the sphingoid bases and ceramides, make up the early products of the sphingolipid synthetic pathways.
What is an R group in sphingolipid?
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.
What are the general classes of sphingolipids?
There are several classes of sphingolipids: the sphingoid base and simple derivatives, ceramides, and complex sphingolipids (Figure 1.5. 1).
What is a sphingolipid composed of?
The sphingolipids, like the phospholipids, are composed of a polar head group and 2 nonpolar tails. The core of a sphingolipid is the long-chain amino alcohol, sphingosine (Figure 21-1). The sphingolipids include the sphingomyelins and glycosphingolipids (the cerebrosides, sulfatides, globosides, and gangliosides).
What type of molecule is sphingosine?
Sphingosine (2-amino-4-octadecene-1,3-diol) is an amino alcohol with an 18-carbon unsaturated alkyl chain, forming a primary component of other sphingolipids.
What are the different types of bond involved in sphingolipids?
Sphingolipids are composed of a sphingosine backbone linked to a fatty acid via an amide bond. There are three main types of sphingolipids, which differ in their hydrophilic attachments: ceramides, sphingomyelins, and glycosphingolipids.
Which component is found in all sphingolipids Mcq?
Which is a characteristic of sphingolipids? They all contain a fatty acid joined to glycerol.
What is sphingosine made of?
Sphingosine is formed by an amino alcohol head group, with two hydroxyls, and one amino group attached to a long unsaturated hydrocarbon chain of typically 18 carbon atoms (see Fig. 17).
What are the two major types of sphingolipids?
Sphingoid bases are the fundamental building blocks of all sphingolipids. The main mammalian sphingoid bases are dihydrosphingosine and sphingosine, while dihydrosphingosine and phytosphingosine are the principal sphingoid bases in yeast.
What are the 4 classes of lipids?
Major types include fats and oils, waxes, phospholipids, and steroids.
How do you identify a sphingolipid?
0:321:55Sphingolipids Mnemonic for MCAT - YouTubeYouTubeStart of suggested clipEnd of suggested clipAs their name suggests. Sphingolipids are built around a sphingosine backbone. We didn't symbolizeMoreAs their name suggests. Sphingolipids are built around a sphingosine backbone. We didn't symbolize this separately since sphingolipids. And sphingosine both sound a lot like sphinx.
What are the 2 linkages present in sphingosine?
Answer and Explanation: Sphingophospholipids consist of sphingosine, fatty acid, phosphate and alcohol in which fatty acid is attached to the sphingosine moiety by an amide linkage. At the same time, the phosphate group is attached to the sphingosine moiety by an ester linkage.
What do all sphingolipids have in common?
Sphingolipid Biosynthesis They share a common structural feature, a so-called sphingoid base backbone that is comprised of an alkyl chain of approximately 18 carbon atoms with one to three hydroxyl groups and one amino group at position 2 (or in one case, at position 1) of the alkyl chain.
Do sphingolipids contain carbohydrates?
1.3. 4 Glycosphingolipids. Glycosphingolipids have a carbohydrate (glucose or galactose for mammalian sphingolipids) attached to the 1-hydroxyl of Cer via a glycosidic bond in the β configuration. More complex sphingolipids have additional carbohydrates (or other modifications of GlcCer or GalCer, such as sulfation).
Is sphingolipid a type of phospholipid?
Sphingolipids are a type of phospholipids that contain a long chain amino alcohol called sphingosine attached to a fatty acid chain. Hence, the core of the sphingolipids is the sphingosine. Moreover, these are the lipids commonly found in nervous tissue that involve with the signal transmission and cell recognition.
Do sphingolipids contain carbohydrates?
1.3. 4 Glycosphingolipids. Glycosphingolipids have a carbohydrate (glucose or galactose for mammalian sphingolipids) attached to the 1-hydroxyl of Cer via a glycosidic bond in the β configuration. More complex sphingolipids have additional carbohydrates (or other modifications of GlcCer or GalCer, such as sulfation).
Does sphingolipids contain glycerol?
Sphingolipids are a second type of lipid found in cell membranes, particularly nerve cells and brain tissues. They do not contain glycerol, but retain the two alcohols with the middle position occupied by an amine.
Do sphingolipids have a carbohydrates?
Ceramide oligosaccharides contain several molecules of carbohydrates as well. Globoside, which is present in red blood cells, is an example of this class of sphingolipid.
Where do sphingolipids form?
The synthesis of complex sphingolipids occurs in the Golgi apparatus. [3] The bulky headgroups of these sphingolipids make flipping between membrane leaflets very unlikely without the aid of flippases. This means that without flippases, sphingolipids are restricted to the lumenal Golgi leaflet/outer leaflet of the plasma membrane. [4] The two main type of complex sphingolipids are phospho- and glycol-sphingolipids.
What is a sphingolipid base?
Sphingoid base & simple derivatives. Sphingolipids are composed of many backbone “sphingoid bases” which are synthesized from serine and a long-chain fatty acyl-CoA. [2,5] If a backbone has not yet been analyzed, it is referred to as a sphinosine, after the original name for the fundamental component of these lipids.
What are the major phosphosphingolipids in fungi?
In insects, it is ceramide phosphoethanolamines. The major phosphosphingolipids in fungi are phytoceramidesphosphoinositols and inositol phosphates. Aquatic organisms typically have sphingolipids where the phosphate has been replaced with a phosphono- or arsenate group. [2] .
What are glycosphingolipids?
Glycosphingolipids have one or more carbohydrate groups in a glycosidic linkage (usually; ceramide phophonositols are an exception). The structure can be seen in Figure 1.5. 4. There are four classifications of glycosphingolipids: 1 Neutral glycosphingolipids: 1 or more uncharged sugars (i.e. glucose, galactose, N-acetylglucosamine, N-acetylgalacoseamine, fucose) [2] 2 Acid glycosphingolipids: ionized functional groups (i.e. phosphate or sulfate) attached to neutral or charged sugars [2] 3 Basic glycosphingolipids [5] 4 Amphoteric glycosphingolipids [5]
How do sphingolipids affect cell signaling?
Sphingolipids affect cell signaling by influencing the properties of receptors directly. The exact pathway for signal transduction varies depending on the exact function of the sphingolipids but there is a general pathway. [2]
How many carbons are in a sphingoid base?
They are fatty acid derivatives of sphingoid bases, linked by amide bonds. They are usually fully saturated or mono-unsaturated and consist of 14-26 carbons, but are sometimes longer. There is sometimes a hydroxyl group on the ω or ω-carbon atom. [2,5] The structure can be seen in Figure 1.5. 2.
What is the disordered phase of a cell?
In the liquid disordered phase, are highly fluid states in which the individual lipids can move unhindered across the surface of the membrane. The packing of the lipids is highly irregular and the lipids themselves are often kinked due to unsaturated fatty acids.
Which group of lipids contains dozens of different sphingolipid species?
At the apex of complexity is the group of lipids known as glycosphingolipids (GSL) which contain dozens of different sphingolipid species differing by both the order and type of sugar residues attached to their headgroups.
What are simple sphingolipids?
The simple sphingolipids serve both as the precursors and the breakdown products of the more complex ones. Importantly, in recent decades, these simple sphingolipids have gained attention for having significant signaling and regulatory roles within cells.
What are sphingolipids? What are their functions?
Modification of this basic structure is what gives rise to the vast family of sphingolipids that play significant roles in membrane biology and provide many bioactive metabolites that regulate cell function. Despite the diversity of structure and function of sphingolipids, their creation and destruction are governed by common synthetic and catabolic pathways. In this regard, sphingolipid metabolism can be imagined as an array of interconnected networks that diverge from a single common entry point and converge into a single common breakdown pathway. In their simplest forms, sphingosine, phytosphingosine and dihydrosphingosine serve as the backbones upon which further complexity is achieved. For example, phosphorylation of the C1 hydroxyl group yields the final breakdown products and/or the important signaling molecules sphingosine-1-phosphate, phytosphingosine-1-phosphate and dihydrosphingosine-1-phosphate, respectively. On the other hand, acylation of sphingosine, phytosphingosine, or dihydrosphingosine with one of several possible acyl CoA molecules through the action of distinct ceramide synthases produces the molecules defined as ceramide, phytoceramide, or dihydroceramide. Ceramide, due to the differing acyl CoAs that can be used to produce it, is technically a class of molecules rather than a single molecule and therefore may have different biological functions depending on the acyl chain it is composed of. At the apex of complexity is the group of lipids known as glycosphingolipids (GSL) which contain dozens of different sphingolipid species differing by both the order and type of sugar residues attached to their headgroups. Since these molecules are produced from ceramide precursors, they too may have differences in their acyl chain composition, revealing an additional layer of variation. The glycosphingolipids are divided broadly into two categories: glucosphingolipids and galactosphingolipids. The glucosphingolipids depend initially on the enzyme glucosylceramide synthase (GCS) which attaches glucose as the first residue to the C1 hydroxyl position. Galactosphingolipids, on the other hand, are generated from galactosylceramide synthase (GalCerS), an evolutionarily dissimilar enzyme from GCS. Glycosphingolipids are further divided based upon further modification by various glycosyltransferases which increases the potential variation in lipid species by several fold. Far more abundant are the sphingomyelin species which are produced in parallel with glycosphingolipids, however they are defined by a phosphocholine headgroup rather than the addition of sugar residues. Although sphingomyelin species all share a common headgroup, they too are produced from a variety of ceramide species and therefore can have differing acyl chains attached to their C-2 amino groups. Whether or not the differing acyl chain lengths in SMs dictate unique functions or important biophysical distinctions has not yet been established. Understanding the function of all the existing glycosphingolipids and sphingomyelin species will be a major undertaking in the future since the tools to study and measure these species are only beginning to be developed (see Fig 1 for an illustrated depiction of the various sphingolipid structures). The simple sphingolipids serve both as the precursors and the breakdown products of the more complex ones. Importantly, in recent decades, these simple sphingolipids have gained attention for having significant signaling and regulatory roles within cells. In addition, many tools have emerged to measure the levels of simple sphingolipids and therefore have become the focus of even more intense study in recent years. With this thought in mind, this chapter will pay tribute to the complex sphingolipids, but focus on the regulation of simple sphingolipid metabolism.
What are the two main categories of glycosphingolipids?
The glycosphingolipids are divided broadly into two categories: glucosphingolipids and galactosphingolipids. The glucosphingolipids depend initially on the enzyme glucosylceramide synthase (GCS) which attaches glucose as the first residue to the C1 hydroxyl position.
How many carbons are in sphingolipids?
An overview of sphingolipid metabolism: from synthesis to breakdown. Sphingolipids constitute a class of lipids defined by their eighteen carbon amino-alcohol backbones which are synthesized in the ER from nonsphingolipid precursors.
What is the enzyme that makes galactosphingolipids?
Galactosphingolipids, on the other hand, are generated from galactosylceramide synthase (GalCerS), an evolutionarily dissimilar enzyme from GCS. Glycosphingolipids are further divided based upon further modification by various glycosyltransferases which increases the potential variation in lipid species by several fold.
Content
The sphingolipids they represent one of the three major families of lipids present in biological membranes. Like glycerophospholipids and sterols, they are amphipathic molecules with a hydrophilic polar region and a hydrophobic apolar region.
ANDstructure
All sphingolipids are derived from an L-serine, which is condensed with a long chain fatty acid to form the sphingoid base, also known as the long chain base (LCB).
characteristics
The fatty acid chains linked by amide bonds to ceramides are commonly saturated, and tend to be longer than those found in glycerophospholipids, which appears to be crucial for their biological activity.
Features
Sphingolipids are essential in animals, plants, and fungi, as well as in some prokaryotic organisms and viruses.
In the lipid "rafts"
In biological membranes, dynamic micro domains with less fluidity can be detected, made up of cholesterol and sphingolipid molecules called lipid rafts.
Byproducts of your metabolism
The most important signaling sphingolipids are the long-chain bases or sphingosines and ceramides, as well as their phosphorylated derivatives, such as sphingosine 1-phosphate.
Sphingolipid groups
There are three subclasses of sphingolipids, all derived from ceramide and differing from each other by polar groups, namely, sphingomyelins, glycolipids, and gangliosides.
Where are sphingolipids found?
Sphingolipids... Sphingomyelins, which are the only phosphorus-containing sphingolipids, are most abundant in nervous tissue, but they also occur in the blood. Abnormal sphingolipid metabolismis a characteristic of a variety of diseases known collectively as sphingolipidosis, or sphingolipodystrophy.
What is a glycolipid?
glycolipid. Glycolipid, any member of a group of fat-soluble substances particularly abundant in tissues of the nervous system of animals. They are members of the class of sphingolipids (q.v.), but differ from the simpler members of that class in that their molecules contain a monosaccharide or disaccharide moiety.….
What is abnormal sphingolipid metabolism?
Abnormal sphingolipid metabolismis a characteristic of a variety of diseases known collectively as sphingolipidosis, or sphingolipod ystrophy. One of the more common forms of cerebralsphingolipidosis (or cerebral lipidosis), formerly called amaurotic familial idiocy, is Tay-Sachs disease(q.v.), a rare, inheritable disorder caused by the accumulation of sphingolipids in the brain. Another inheritable lipidosis is Niemann-Pick disease(q.v.), in which lecithinand sphingomyelin accumulate in various body tissues, such as the spleen and the liver.
Which type of tissue contains gangliosides?
Gangliosides, most abundant in nerve tissue (especially the gray matter of brain) and certain other tissues (e.g.,spleen) are similar to cerebrosides except that, in addition to the sugar component, they contain several other molecules of carbohydrate(N-acetylglucosamine or N-acetylgalactosamine and N-acetylneuramine).
What are the sphingolipids?
The sphingolipid class of cell membrane lipids includes the sphingoid bases, ceramides (sphingoid bases with N-linked acyl groups), and complex sphingolipids based on ceramide and containing polar head groups. The committed step in sphingolipid biosynthesis is the condensation of palmitate with serine, which is catalyzed by serine palmitoyltransferase (SPT), a pyridoxal 5′-phosphate-dependent enzyme composed of two subunits and requiring (at least in yeast) another small subunit for maximal activity [2]. SPT generates 3-ketosphinganine, which is then reduced to dihydrosphingosine (DHS). The N-linked addition of a fatty acid to DHS, catalyzed by dihydroceramide synthase, yields dihydroceramide, which is subsequently desaturated to form ceramide in mammalian cells, or hydroxylated to form phytoceramide in yeast. From ceramide a variety of complex sphingolipids are derived. For example, complex glycosphingolipids including cerebrosides are formed by the addition of sugar groups to the ceramide backbone, and gangliosides are formed by the further addition of sialic acid. Sphingomyelin (SM) is generated by the transfer of a phosphocholine headgroup from phosphatidylcholine to ceramide. Each of these sphingolipid classes has distinct structural and/or functional roles [3 ].
What is the sphingolipid structure?
10.2 Overview of Sphingolipids Metabolism. Sphingolipids refer to a class of complex phospholipids with a core hydrophobic structure of ceremide, which is composed of a sphingosine head and a long-chain fatty acid chain. They are essential components of plasma membranes.
How are complex sphingolipids formed?
For example, complex glycosphingolipids including cerebrosides are formed by the addition of sugar groups to the ceramide backbone, and gangliosides are formed by the further addition of sialic acid.
What is the main source of S1P?
Blood cells are the biggest sources of S1P, in particular erythrocyte, but vascular and lymphatic endothelial cells also synthesize and release S1P. Endothelial cells express S1P receptors that are stimulated by thrombin and in hypoxia conditions [97 ].
What is the role of sphingolipids in drug development?
With these roles, sphingolipids and sphingolipid synthesis emerge as a logical target for drug development, with the majority of the thus-far tested drugs targeting enzymes that are involved in the production of various sphingolipid subtypes.
What are the roles of sphingolipids in the cell cycle?
Sphingolipids have a significant role as structural components in cell membranes as well as signaling molecules in regulatory pathways, such as cell cycle arrest, apoptosis, senescence, and differentiation. With these roles, sphingolipids and sphingolipid synthesis emerge as a logical target for drug development, with the majority of the thus-far tested drugs targeting enzymes that are involved in the production of various sphingolipid subtypes. The goal of these novel therapies is to adjust the sphingolipid metabolism so as to accumulate ceramine and to decrease sphingosine-1-phosphate, which is a tumor-promoting lipid. The target enzymes of human sphingolipid pathway are serine palmitoyl transferase, ceramine synthase, ceramidase, sphingosine kinase, glucosylceramide synthase, and 1-O-acylceramide synthase. Several drugs targeting these enzymes, including 4-HPR, PSC 833, daunorubicin, B13, safingol, PPMP, PPPP, butyldeoxynojiriMYCin and phenoxodiol, are currently in preclinical or clinical trials (Reynolds, 2004; Zeidan, 2007; reviewed in Oskouian and Saba, 2010). To date, the approaches taken in general to target sphingolipid metabolism for cancer therapy have involved: (a) synthetic ceramide analogs; (b) small-molecule inhibitors of enzymes that catabolize ceramide; (c) the inhibition of SK; and (d) S1P receptor antagonists. Although many ceramide analogs have been created and have provided interesting results in vitro, they have the potential to interact with many other targets, such that toxicity becomes a major concern for their clinical use. Some drugs that have been used to treat sphingolipidosis (a lipid-storage disease) target enzymes in the sphingolipid pathway, and have shown potential as anti-cancer drugs, with initial tests in model systems showing much promise (Oskouian and Saba, 2010 and references therein). The inhibition of S1P synthesis by blocking SK activity appears to be useful for enhancing the response of a cancer to chemotherapy, both in vitro and in animal models ( Oskouian and Saba, 2010 and references therein). The chemotherapeutic agent fenretinide is cytotoxic towards a variety of tumors, including neuroblastoma, and was shown to increase ceramide generation via de novo synthesis through an activation of both SPT and ceramide synthase ( Wang et al., 2001 ). These and other examples of tools for regulating sphingolipid pathways are currently under development, and present an interesting, novel therapeutic strategy against cancer.
What are the two products of hydrolysis?
Sphingolipids are characterized by the presence of sphingosine as one of their moieties:Derived lipid and a water-soluble compound are the other products of hydrolysis.
Overview
Types
Simple sphingolipids, which include the sphingoid bases and ceramides, make up the early products of the sphingolipid synthetic pathways.
• Sphingoid bases are the fundamental building blocks of all sphingolipids. The main mammalian sphingoid bases are dihydrosphingosine and sphingosine, while dihydrosphingosine and phytosphingosine are the principal sphingoid bases in yeast. Sphingosine, dihydrosphingosine, a…
Structure
The long-chain bases, sometimes simply known as sphingoid bases, are the first non-transient products of de novo sphingolipid synthesis in both yeast and mammals. These compounds, specifically known as phytosphingosine and dihydrosphingosine (also known as sphinganine, although this term is less common), are mainly C18 compounds, with somewhat lower levels of C20 bases. Ceramides and glycosphingolipids are N-acyl derivatives of these compounds.
Mammalian sphingolipid metabolism
De novo sphingolipid synthesis begins with formation of 3-keto-dihydrosphingosine by serine palmitoyltransferase. The preferred substrates for this reaction are palmitoyl-CoA and serine. However, studies have demonstrated that serine palmitoyltransferase has some activity toward other species of fatty acyl-CoA and alternative amino acids, and the diversity of sphingoid bases has …
Functions of mammalian sphingolipids
Sphingolipids are commonly believed to protect the cell surface against harmful environmental factors by forming a mechanically stable and chemically resistant outer leaflet of the plasma membrane lipid bilayer. Certain complex glycosphingolipids were found to be involved in specific functions, such as cell recognition and signaling. Cell recognition depends mainly on the physical properties of the sphingolipids, whereas signaling involves specific interactions of the glycan str…
Other sphingolipids
Sphingolipids are universal in eukaryotes but are rare in bacteria and archaea. Bacteria that do produce sphingolipids are found in family Sphingomonadaceae, the FCB group (some members), and some parts of Deltaproteobacteria.
Because of the incredible complexity of mammalian systems, yeast are often used as a model organism for working out new pathways. These single-celled organisms are often more genetical…
Disorders
There are several disorders of sphingolipid metabolism, known as sphingolipidoses. The main members of this group are Niemann-Pick disease, Fabry disease, Krabbe disease, Gaucher disease, Tay–Sachs disease and Metachromatic leukodystrophy. They are generally inherited in an autosomal recessive fashion, but notably Fabry disease is X-linked. Taken together, sphingolipidoses have an incidence of approximately 1 in 10,000, but substantially more in certai…
Additional images
• Sphingosine