Fatty acids ceramide

The remarkable barrier function of the skin is primarily located in the stratum corneum (SC), the thin, outermost layer of the epidermis. The SC consists of several layers of protein-filled corneocytes (i.e., terminally differentiated keratinocytes) embedded in an extracellular lipid matrix. Attached to the outer cor-neocyte envelope are long-chain covalently bound cer-amides that interact with the lipids of the extracellular space. These lipids are composed primarily of free fatty acids, ceramides, and cholesterol arranged in multiple lamellae.f Passive permeation across the SC is believed to occur primarily via the intercellular... 

Ceramides can be rapidly formed from erythro or threo long-chain bases. The specificity of this acylation by acyl-CoAs has been studied in brain and other tissues (cf. Stoffel, 1971). The significance of the nature of the fatty acid moiety in ceramides is well seen when the glycosylation of ceramides is considered hydroxy fatty acid containing ceramides accept predominantly galactose while non-hydroxy fatty acid ceramides accept glucose. 

A similar method separated the following lipids from human fibroblasts into the following groups CE, TAG, phytols, C, diglycerides, fatty acids, ceramides, PE, PS, SM, and LPC on a silica column (ELSD). Working curves were shown for CE, TAG, C, ceramide, PC, and SM fractions. A two-ramp 60-min 99/1/0/0/0-+ 0/0/20/80/0 -> 0/0/0/50/50 hexane/THF/chloroform/IPA/water gradient was used. Samples containing 30 nmol total lipid phosphorus were used [433],... 

Ceramide types III and IV were isolated from stratum comeum lipid extracts and separated from cholesterol, free fatty acids, and triglycerides on a silica column (ELSD) in <15min using a 19/1 hexane/ethanol mobile phase [717]. Related compound classes (hydroxy fatty acid ceramide, C2 ceramide, sphingolipid, phyto-sphingosine) were separated on a silica column using a 90/10/1/1 chloroform/ ethanol/triethylamine/formic acid mobile phase. In this case elution was complete in 10 min. 

The benzoic anhydride derivatives of ceramide-related compounds (fatty acids, non-hydroxy fatty acid ceramide, dihydroceramide, sphingosine, sphinganine) were separated on a silica column (A = 230nm) using a 99.44/0.45 cyclohexane/IPA mobile phase [719]. Elution was complete in 8 min. Good resolution was achieved. 

Figure 3 Structures of the three dominant classes of lipids found in the stratum comeum fatty acid, ceramides, and sterols.

Hydroxy fatty acid) ceramide -f- UDP galactose — c mide galactoside... 

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. 

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... 

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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