Ceramide
Ceramides are a family of
.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 the cell membrane and release ceramide. Second, the de novo pathway creates ceramide from less complex molecules. Third, in the "salvage" pathway, sphingolipids that are broken down into sphingosine are reused by reacylation to form ceramide.
Sphingomyelin hydrolysis
De novo
De novo synthesis of ceramide begins with the condensation of
Salvage pathway
Constitutive degradation of sphingolipids and glycosphingolipids takes place in the acidic subcellular compartments, the late endosomes and the
Physiological roles
Pathology
As a bioactive lipid, ceramide has been implicated in a variety of physiological functions including
Several distinct ceramides potently predict
Ceramides induce skeletal muscle insulin resistance when synthesized as a result of saturated fat activation of
Apoptosis
One of the most studied roles of ceramide pertains to its function as a proapoptotic molecule.
Skin
The
Epidermal ceramides have a diversity of structures and can be broadly classified as AS and NS ceramides; ADS and NDS dihydroceramides; AH, EOH, and NH 6-hydroxyceramides; AP and NP phytoceramides; and EOH and EOS acylceramides, see figure.
[18] The diversity of ceramide structures undoubtedly plays an important role in the unique attributes of the stratum corneum across different body sites. For example, the stratum corneum of the face is thin and flexible to accommodate different facial expressions. In contrast, the stratum corneum covering the heel of the foot is thick and rigid to protect against trauma. Matching these structural changes, there are body-site specific alterations in the epidermal lipidome, including changes in the relative abundance of the different epidermal ceramide structures.[18]
Similar to body site-specific alterations in ceramide abundance, there are also well-characterized changes in epidermal ceramide expression in patients with inflammatory skin diseases. In the hyperplastic disorder psoriasis, investigators have reported an increase in AS and NS ceramides and a decrease in EOS, AP, and NP ceramides, which may contribute to a defect in the skin's water impermeability barrier.[23][24][22] Studying ceramide expression in atopic dermatitis and psoriasis patients, other investigators have reported that rather than focusing on ceramide classes, 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.[18]
Hormonal
Inhibition of ceramide synthesis with
Substances known to induce ceramide generation
- Anandamide
- Ceramidase inhibitors
- Chemotherapeutic agents
- Fas ligand
- Endotoxin
- Homocysteine[27]
- Heat
- Hydroxypalmitoyl Sphinganine[28][29]
- Gamma interferon
- Ionizing radiation[2][30]
- Matrix metalloproteinases[27]
- Niacinamide
- Reactive oxygen species[27]
- Sphingosine[citation needed]
- cannabinoids[31]
- TNF-alpha[27]
- 1,25 Dihydroxy vitamin D
Mechanism by which ceramide signaling occurs
Currently, the means by which ceramide acts as a signaling molecule are not clear.
One hypothesis is that ceramide generated in the
Ceramide has also been shown to form organized large channels traversing the mitochondrial outer membrane. This leads to the egress of proteins from the intermembrane space.[32][33][34]
Related diseases
In the metabolic disease combined malonic and methylmalonic aciduria (CMAMMA) due to ACSF3, a massive altered composition of complex lipids occurs as a result of impaired mitochondrial fatty acid synthesis (mtFAS).[35][36] For example, while the concentration of sphingomyelin is noticeably increased, the concentration of ceramides is proportionally decreased.[35]
Uses
Ceramides may be found as ingredients of some topical skin medications used to complement treatment for skin conditions such as
Ceramide in bacteria
Ceramide is rarely found in bacteria.[40] Bacteria of family Sphingomonadaceae, however, contain it.
Ceramide phosphoethanolamine
Ceramide phosphoethanolamine (CPE) is a
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- ^ Whitney P. Bowe; Leon H. Kircik (August 2014). "The Importance of Photoprotection and Moisturization in Treating Acne Vulgaris". Journal of Drugs in Dermatology. 13 (8): 89. Archived from the original on 2022-01-02. Retrieved 2022-01-02.
- ^ "Hydroxypalmitoyl Sphinganine (Explained + Products)". incidecoder.com. Archived from the original on 12 July 2021. Retrieved 12 July 2021.
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- ^ "Ceramides - Skin Lipids That Keep Skin Moisturized". Archived from the original on 6 April 2016. Retrieved 29 January 2015.
- ^ "Safety Assessment of Ceramides as Used in Cosmetics" (PDF). Cosmetic Ingredient Review. May 16, 2014. Archived (PDF) from the original on January 13, 2021. Retrieved August 26, 2015.
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External links
- Ceramides at the U.S. National Library of Medicine Medical Subject Headings (MeSH)