Ceramides fatty acids

The success of the Potts-Guy equation led many authors to advocate a single mechanism as the rate determining step for permeation through the skin barrier for all or at least a wide range of solutes diffusion was assumed to occur primarily via the interkeratinocyte lipids of the stratum corneum, a mixture of ceramides, fatty acids, and sterols. While from a macroscopic point of view these lipids may be modeled as a bulk solvent, on a microscopic scale they... 

The major lipids found in the stratum comeum are ceramides, fatty acids, and cholesterol. Free fatty acids make up 10-15% of the lipid mass of the stratum corneum and predominantly consist of straight-chain saturated species ranging from 14 to 28 carbons in length. Cholesterol, a major lipid found in the stratum corneum, represents approximately 25% of the total stratum comeum lipid while cholesterol sulfate accounts for another 5%. 

The exact mechanism of action of moisturizers and emollients is still unknown. Theoretically, the improvement in the barrier function could be due to absorption of the moisturizer into the delipidized stratum corneum, acting as an effective barrier, as suggested in a study on the effect of petrolatum (Ghadially et al. 1992). Due to a better knowledge of the structural organization of the horny layer with corneocytes embedded in between lipid bilayers (ceramides, cholesterol and free fatty acids in approximately equal quantities), new emollients could be developed to supply the missing elements in the bilayer structure after acute or chronic irritant contact. However, applications of ceramides, linoleic acid and a variety of other fatty acids alone have been reported to actually delay barrier recovery in acetone-treated murine skin, despite the fact that these lipids are required for barrier homeostasis. The only treatments that allowed normal barrier recovery were applications of complete mixtures of ceramide, fatty acid and cholesterol, or pure cholesterol (Man et al. 

Kiarash A, Boyd B, Lingwood CA Glycosphingolipid receptor function is modified by fatty acid content Verotoxin 1 and verotoxin 2c preferentially recognize different globotriaosyl ceramide fatty acid homologues. J. Biol. Chem. 1994 269 11138-11146. 

Arab, S. and Lingwood, C., Intracellular targeting of the endoplasmic reticulum/nuclear envelope by retrograde transport may determine cell hypersensitivity to Verotoxin sodium butyrate or selection of drug resistance may induce nuclear toxin targeting via globotriosyl ceramide fatty acid isoform traffic, J Cell Physiol, 1998, 777 646 660. 

FIGURE8.il Formation of an amide linkage between a fatty acid and sphingosine produces a ceramide. 

Acetyl coenzyme A is the precursor of both cholesterol and fatty acids 39 Phosphatidic acid is the precursor of all glycerolipids 42 Sphingolipids are biosynthesized by adding head groups to the ceramide moiety 44... 

The amino group of sphingosine is acylated with long-chain fatty acids and the N-acylated product is termed a ceramide (Fig. 3-3). C-l of ceramide is linked to different... 

Figure 12.12 Sphingomyelins. Sphingomyelins are esters of a ceramide and phospho-ryl choline. However, similar compounds are ceramide-1-phosphoryl ethanolamines and phosphono forms of sphingolipids. Ceramides W-acyl-sphingosines) are amides of a long chain di- or trihydroxy base containing 12 to 22 carbon atoms, of which sphingosine (4-sphingenine) is the commonest, and a long chain fatty acid whose acyl chain is shown by R1. This may contain up to 26 carbon atoms.

The stratum corneum consists of separated, nonviable, cornified, almost nonpermeable corneocytes embedded into a continuous lipid bilayer made of various classes of lipids, for example, ceramides, cholesterol, cholesterol esters, free fatty acids, and triglycerides [6], Structurally, this epidermis layer is best described by the so-called brick-and-mortar model [7], The stratum corneum is crucial for the barrier function of the skin, controlling percutaneous absorption of dermally applied substances and regulating fluid homeostasis. The thickness of the stratum corneum is usually 10-25 /an, with exceptions at the soles of the feet and the palms, and swells several-fold when hydrated. All components of the stratum corneum originate from the basal layer of the epidermis, the stratum germinativum. 

Figure 11.24 A summary of the reactions involved in synthesis of sphingomyelin. Reaction between serine and palmitoyl-CoA produces 3-oxosphinganine, which is converted to sphingamine. Attachment of a Long-chain fatty acid to the amino group of sphinganine produces dihydroxyceramide. Ceramide reacts with phosphatidylcholine the phosphocholine component forms an ester bond with the hydroxyl group at position one of ceramide.

Attachment of another long-chain fatty acid in an amide linkage to the amino group of sphingosine forms a ceramide, the parent compound for many of the physiologically important sphingolipids. 

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