Synthesis and degradation pathways, functions, and pathology of ceramides and epidermal acylceramides

Prog Lipid Res. 2016 Jul:63:50-69. doi: 10.1016/j.plipres.2016.04.001. Epub 2016 Apr 21.


Ceramide (Cer) is a structural backbone of sphingolipids and is composed of a long-chain base and a fatty acid. Existence of a variety of Cer species, which differ in chain-length, hydroxylation status, and/or double bond number of either of their hydrophobic chains, has been reported. Ceramide is produced by Cer synthases. Mammals have six Cer synthases (CERS1-6), each of which exhibits characteristic substrate specificity toward acyl-CoAs with different chain-lengths. Knockout mice for each Cer synthase show corresponding, isozyme-specific phenotypes, revealing the functional differences of Cers with different chain-lengths. Cer diversity is especially prominent in epidermis. Changes in Cer levels, composition, and chain-lengths are associated with atopic dermatitis. Acylceramide (acyl-Cer) specifically exists in epidermis and plays an essential role in skin permeability barrier formation. Accordingly, defects in acyl-Cer synthesis cause the cutaneous disorder ichthyosis with accompanying severe skin barrier defects. Although the molecular mechanism by which acyl-Cer is generated was long unclear, most genes involved in its synthesis have been identified recently. In Cer degradation pathways, the long-chain base moiety of Cer is converted to acyl-CoA, which is then incorporated mainly into glycerophospholipids. This pathway generates the lipid mediator sphingosine 1-phosphate. This review will focus on recent advances in our understanding of the synthesis and degradation pathways, physiological functions, and pathology of Cers/acyl-Cers.

Keywords: Acylceramide; Ceramide; Fatty acid; Long-chain base; Skin barrier; Sphingolipid.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetyltransferases / metabolism
  • Alcohol Oxidoreductases / metabolism
  • Animals
  • Ceramides / chemistry
  • Ceramides / metabolism*
  • Dermatitis, Atopic / metabolism
  • Dermatitis, Atopic / pathology
  • Epidermis / metabolism
  • Fatty Acids / metabolism
  • Humans
  • Serine C-Palmitoyltransferase / metabolism
  • Sphingosine N-Acyltransferase / metabolism
  • Substrate Specificity


  • Ceramides
  • Fatty Acids
  • Alcohol Oxidoreductases
  • 3-ketodihydrosphingosine reductase
  • Acetyltransferases
  • Sphingosine N-Acyltransferase
  • Serine C-Palmitoyltransferase