Ceramides
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Ceramides
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. The word ''ceramide'' comes from the Latin ''cera'' (wax) and ''amide''. Ceramide is a component of vernix caseosa, the waxy or cheese-like white substance found coating the skin of newborn human infants. Pathways for ceramide synthesis There are three major pathways of ceramide generation. First, the sphingomyelinase pathway uses an enzyme to break down sphingomyelin in t ...
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Sphingolipid
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. 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 phy ...
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Sphingolipids General Structures
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. 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 ...
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Lipid Signaling
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 (such as monoamine neurotransmission) because lipids can freely diffuse through membranes (''see osmosis''). 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. Sphingolipid second messengers Ceramide Ceramide (Cer) can be generated by the breakdown of sphingomyelin (SM) by sphingomyelinases (SMases), which are enzymes that hydrolyze the phosphocholine group fr ...
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Sphingomyelin
Sphingomyelin (SPH, ˌsfɪŋɡoˈmaɪəlɪn) 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. Sphingomyelin was first isolated by German chemist Johann L.W. Thudicum in the 1880s. The structure of sphingomyelin was first reported in 1927 as N-acyl-sphingosine-1-phosphorylcholine. Sphingomyelin content in mammals ranges from 2 to 15% in most tissues, with higher concentrations found in nerve tissues, red blood cells, and the ocular lenses. Sphingomyelin has significant structural and functional roles in the cell. It is a plasma membrane component and participates in many signaling pathways. The metabolism of ...
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Vernix Caseosa
Vernix caseosa, also known as vernix or birthing custard, is the waxy white substance found coating the skin of newborn human babies. It is produced by dedicated cells and is thought to have some protective roles during fetal development and for a few hours after birth. Etymology In Latin, ''vernix'' means ''varnish'' and ''caseosa'' means ''cheesy''. The term was first published in 1846 in the ''Dunglison Dictionary of Medical Sciences''. In-utero development Vernix is produced during a distinct phase of the epidermal development. Around the 21st week of gestation, periderm cells are being shed and replaced with stratum corneum; these shedding mix with secretions of sebum by the sebaceous glands to form vernix, which gradually covers the body in an anteroposterior and dorsoventral pattern. Vernix, in itself, is also believed to aid in the formation of stratum corneum. By early third trimester, the process is complete. Soon enough, part of the vernix is emulsified by increa ...
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Fatty Acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, from 4 to 28. Fatty acids are a major component of the lipids (up to 70% by weight) in some species such as microalgae but in some other organisms are not found in their standalone form, but instead exist as three main classes of esters: triglycerides, phospholipids, and cholesteryl esters. In any of these forms, fatty acids are both important dietary sources of fuel for animals and important structural components for cells. History The concept of fatty acid (''acide gras'') was introduced in 1813 by Michel Eugène Chevreul, though he initially used some variant terms: ''graisse acide'' and ''acide huileux'' ("acid fat" and "oily acid"). Types of fatty acids Fatty acids are classified in many ways: by length, by saturation vs unsa ...
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Dihydroceramide Desaturase
Dihydroceramide desaturase is the enzyme involved in the conversion of dihydroceramide into ceramide by inserting the 4,5-''trans''-double bond to the sphingolipid backbone of dihydroceramide. DDase require the and the NAD(P)H Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an aden ... as cofactor. The activity of DDase is influenced by several factors as # alkyl chain length of the sphingoid base (in the order C18 > C12 > C8) and fatty acid (C8 > C18) # The stereochemistry of the sphingoid base (D-erythro- > L-threo-dihydroceramides) # the nature of the headgroup, with the highest activity with dihydroceramide, but some (approximately 20%) activity with dihydroglucosylceramide # The ability to utilize alternative reductants like ascorbic acid could substitute for a reduced pyridine nuc ...
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Dihydrosphingosine
Safingol is a lyso-sphingolipid protein kinase inhibitor. It has the molecular formula C18H39NO2 and is a colorless solid. Medicinally, safingol has demonstrated promising anticancer potential as a modulator of multi-drug resistance and as an inducer of necrosis. The administration of safingol alone has not been shown to exert a significant effect on tumor cell growth.Schwartz, G. K., Haimovitz-Friedman, A., Dhupar, S. K., Ehleiter, D., Maslak, P., Lai, L., ... & Albino, A. P. (1995). Potentiation of apoptosis by treatment with the protein kinase C-specific inhibitor safingol in mitomycin C-treated gastric cancer cells. Journal of the National Cancer Institute, 87(18), 1394-1399. However, preclinical and clinical studies have shown that combining safingol with conventional chemotherapy agents such as fenretinide, vinblastine, irinotecan and mitomycin C can dramatically potentiate their antitumor effects. Currently in Phase I clinical trials, it is believed to be safe to co-admin ...
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Serine Palmitoyl Transferase
In enzymology, a serine C-palmitoyltransferase () is an enzyme that catalyzes the chemical reaction: :palmitoyl-CoA + L-serine \rightleftharpoons CoA + 3-dehydro-D-sphinganine + CO2 Thus, the two substrates of this enzyme are palmitoyl-CoA and L-serine, whereas its 3 products are CoA, 3-dehydro-D-sphinganine, and CO2. This reaction is a key step in the biosynthesis of sphingosine which is a precursor of many other sphingolipids. This enzyme participates in sphingolipid metabolism. It employs one cofactor, pyridoxal phosphate. Nomenclature This enzyme belongs to the family of transferases, specifically those acyltransferases transferring groups other than aminoacyl groups. The systematic name of this enzyme class is palmitoyl-CoA:L-serine C-palmitoyltransferase (decarboxylating). Other names in common use include: * serine palmitoyltransferase, * SPT, 3-oxosphinganine synthetase, and * acyl-CoA:serine C-2 acyltransferase decarboxylating. Structure Serine C ...
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Serine
Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form under biological conditions), and a side chain consisting of a hydroxymethyl group, classifying it as a polar amino acid. It can be synthesized in the human body under normal physiological circumstances, making it a nonessential amino acid. It is encoded by the codons UCU, UCC, UCA, UCG, AGU and AGC. Occurrence This compound is one of the naturally occurring proteinogenic amino acids. Only the L- stereoisomer appears naturally in proteins. It is not essential to the human diet, since it is synthesized in the body from other metabolites, including glycine. Serine was first obtained from silk protein, a particularly rich source, in 1865 by Emil Cramer. Its name is derived from the Latin for silk, ''sericum''. Serine's structure w ...
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Hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysis is the cleavage of biomolecules where a water molecule is consumed to effect the separation of a larger molecule into component parts. When a carbohydrate is broken into its component sugar molecules by hydrolysis (e.g., sucrose being broken down into glucose and fructose), this is recognized as saccharification. Hydrolysis reactions can be the reverse of a condensation reaction in which two molecules join into a larger one and eject a water molecule. Thus hydrolysis adds water to break down, whereas condensation builds up by removing water. Types Usually hydrolysis is a chemical process in which a molecule of water is added to a substance. Sometimes this addition causes both the substance and water molecule to split into two parts. ...
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