Ceramides are a family of waxy lipid molecules.
A ceramide is composed of sphingosine and a fatty acid.
Ceramide represents the alkyl portion of a fatty acid.
Ceramides are a family of waxy lipid molecules: composed of sphingosine and a fatty acid joined by an amide bond.
Ceramides are found in high concentrations within the cell membrane as they are component lipids that make up sphingomyelin, one of the major lipids in the lipid bilayer.
Ceramide can participate in a variety of cellular signaling processes including regulating differentiation, proliferation, and programmed cell death of cells.
Ssphingomyelinase pathways uses an enzyme to break down sphingomyelin in the cell membrane and release ceramide.
A de novo pathway creates ceramide from less complex molecules.
Sphingolipids that are broken down into sphingosine are reused by reacylation to form ceramide.
The hydrolysis of sphingomyelin is catalyzed by the enzyme sphingomyelinase.
When ionizing radiation causes apoptosis in some cells, the radiation leads to the activation of sphingomyelinase in the cell membrane and ultimately, to ceramide generation.
De novo synthesis of ceramide occurs in the endoplasmic reticulum, and subsequently transported to the Golgi apparatus by either vesicular trafficking or the ceramide transfer protein.
At the Golgi apparatus, ceramide can be further metabolized to other sphingolipids, such as sphingomyelin and the complex glycosphingolipids.
Degradation of sphingolipids and glycosphingolipids takes place in endosomes and the lysosomes, with the end goal of producing sphingosine.
Sphingosine may then contribute to the generation of ceramides.
Ceramide can be hydrolyzed by acid ceramidase to form sphingosine and a free fatty acid, both of which are able to leave the lysosome, unlike ceramide.
The ceramide synthase family members probably trap free sphingosine released from the lysosome at the surface of the endoplasmic reticulum or in endoplasmic reticulum-associated membranes.
The salvage pathway has been estimated to contribute from 50% to 90% of sphingolipid biosynthesis.
Ceramide is a bioactive lipid has been implicated in a variety of physiological functions: apoptosis, cell growth arrest, differentiation, cell senescence, cell migration and adhesion.
Ceramide and its downstream metabolites maybe involved pathological states including cancer, neurodegeneration, diabetes, microbial pathogenesis, obesity, and inflammation.
Several ceramides potently predict major adverse cardiovascular events.
Ceramide levels are positively correlated with inflammation and oxidative stress in the liver.
Ceramide levels are positively correlated with onset and progression of non-alcoholic fatty liver disease (NAFLD) is associated with elevated ceramide in hepatocytes.
Dietary intake of saturated fat increases serum ceramide and increase insulin resistance.
Although initial studies showed increased insulin resistance in muscle, subsequent studies also showed increased insulin resistance in liver and adipose tissue.
Limiting ceramide synthesis or increasing ceramide degradation lead to improved health with reduced insulin resistance and reduced fatty liver disease.
Ceramides induce skeletal muscle insulin resistance when synthesized as a result of saturated fat activation of TLR4 receptors.
Unsaturated fat does not have this effect.
Ceramides induce insulin resistance in many tissues by inhibition of Akt/PKB signaling.
Aggregation of LDL cholesterol by ceramide causes LDL retention in arterial walls, leading to atherosclerosis.
Ceramides cause endothelial dysfunction by activating protein phosphatase 2.
In mitochondria, ceramide suppresses the electron transport chain and induces production of reactive oxygen species.
Apoptosis, or programmed cell death, is essential for the maintenance of normal cellular homeostasis and is an important physiological response to many forms of cellular stress.
Ceramide accumulation has been found following treatment of cells with a number of apoptotic agents, including ionizing radiation,
UV light, TNF-alpha, and chemotherapeutic agents.
Ceramide has been termed the “tumor suppressor lipid” inducing apoptosis.
The stratum corneum of the skin is the outermost layer of the epidermis, and is composed of terminally differentiated and enucleated corneocytes that reside within a lipid matrix.
Ceramides with cholesterol and free fatty acids form the lipid mortar, a water-impermeable barrier that prevents evaporative water loss.
The epidermal lipid matrix is composed of an equimolar mixture of ceramides (~50% by weight), cholesterol (~ 25% by weight), and free fatty acids (~15% by weight), with smaller quantities of other lipids also being present.
The epidermal lipid matrix barrier also protects against the entry of microorganisms.
There is a diversity of ceramide structures undoubtedly in the stratum corneum across different body sites.
The stratum corneum of the face is thin and flexible accommodating different facial expressions.
The stratum corneum covering the heel of the foot is thick and rigid to protect it against trauma.
There are body-site specific alterations in the epidermal lipidome, in different epidermal ceramide structures.
Changes in epidermal ceramide expression occurs in patients with inflammatory skin diseases.
In the hyperplastic disorder psoriasis, ceramide decreases may contribute to a defect in the skin’s water impermeability barrier.
Ceramide sphingoid base length and fatty acid chain length have the strongest influence on the likelihood of a particular ceramide structure being upregulated or downregulated in inflamed skin.
Ceramide that is generated in the plasma membrane enhances membrane rigidity and stabilizes smaller lipid platforms known as lipid rafts, allowing them to serve as platforms for signalling molecules.
Lipid rafts can induce localized changes in the other leaflet of the bilayer, they can potentially serve as the link between signals from outside the cell to signals to be generated within the cell.
Ceramide forms organized large channels traversing the mitochondrial outer membrane, leading to the egress of proteins from the intermembrane space.
Ceramides may be found as ingredients of some topical skin medications used treat skin conditions such as eczema.
Ceramides are also used in cosmetic products such as some soaps, shampoos, skin creams, and sunscreens.
It is found in high concentrations within the cell membrane of eukaryotic cells.
They are component lipids that make up sphingomyelin, one of the major lipids in the lipid bilayer.
Ceramide can regulate differentiation, proliferation, and programmed cell death of cells.
There are three major pathways of ceramide generation: sphingomyelinase pathway, de novo pathway, and the salvage pathway.
It is a bioactive lipid.
Its activity has been implicated: apoptosis, cell growth arrest, differentiation, cell senescence, cell migration and adhesion.
May play a role in a number of pathological states including cancer, neurodegeneration, diabetes, microbial pathogenesis, obesity, and inflammation.
Ceramides induce skeletal muscle insulin resistance.
They induce insulin resistance in many tissues.
They inhibit Akt/PKB signaling.
The aggregation of LDL cholesterol by ceramide causes LDL retention in arterial walls, leading to atherosclerosis.
It cause endothelial dysfunction by activating protein phosphatase 2.
It suppresses mitochondrial electron transport chain and induces production of reactive oxygen species.
Functions as a proapoptotic molecule.
Ceramide accumulation has been found following treatment of cells with a number of apoptotic agents including ionizing radiation, and chemotherapy.
It has apoptosis-inducing effects in cancer cells.
Ceramide has been termed the tumor suppressor lipid.
It is thought ceramide functions upstream of the mitochondria in inducing apoptosis, but the mechanism by which this lipid regulates apoptosis remains unproven.
It is the main component of the stratum corneum of the epidermis layer of human skin.
The stratum corneum is composed of 50% ceramides, 25% cholesterol, and 15% free fatty acids.
Ceramide, along with cholesterol and saturated fatty acids, create a water-impermeable, organ that prevents excessive water loss due to evaporation as well as a barrier against the entry of microorganisms.
In psoriasis the water permeability barrier is compromised.
Ceramide VI is the most abundant ceramide of the skin, along with ceramide II.
The extracellular lipid lamellae of the stratum corneum contains ultra long chain (C28-C36) ceramides.
With aging ceramide and cholesterol in the stratum corneum of humans decrease.
Increased ceramide synthesis leads to both leptin resistance and insulin resistance.
An elevated level of ceramide leads to insulin resistance.
Substances known to induce ceramide generation:
Anandamide
Ceramidase inhibitors
Chemotherapeutic agents
Fas ligand
Endotoxin
Homocysteine
Heat
Gamma interferon
Ionizing radiation
Matrix metalloproteinases
Niacinamide
Reactive oxygen species
Tetrahydrocannabinol and other cannabinoids
TNF-alpha
1,25 Dihydroxy vitamin D
It is hypothesized ceramide generated in the plasma membrane enhances membrane rigidity.
Ceramides are ingredients in some topical skin medications used to complement treatment for skin conditions such as eczema..
They are also used in cosmetic products such as some soaps, shampoos, skin creams, and sunscreens Ceramide is rarely found in bacteria.