Ceramide

Ceramide is a component of vernix caseosa, the waxy or cheese-like white substance found coating the skin of newborn human infants.

[2] De novo synthesis of ceramide begins with the condensation of palmitate and serine to form 3-keto-dihydrosphingosine.

In turn, 3-keto-dihydrosphingosine is reduced to dihydrosphingosine, which is then followed by acylation by the enzyme (dihydro)ceramide synthase to produce dihydroceramide.

[3] Constitutive degradation of sphingolipids and glycosphingolipids takes place in the acidic subcellular compartments, the late endosomes and the lysosomes, with the end goal of producing sphingosine.

In the case of glycosphingolipids, exohydrolases acting at acidic pH optima cause the stepwise release of monosaccharide units from the end of the oligosaccharide chains, leaving just the sphingosine portion of the molecule, which may then contribute to the generation of ceramides.

[3] Roles for ceramide and its downstream metabolites have also been suggested in a number of pathological states including cancer, neurodegeneration, diabetes, microbial pathogenesis, obesity, and inflammation.

[5][6] Several distinct ceramides potently predict major adverse cardiovascular events (MACE), namely C16:0, C18:0, and C24:1, although C24:0 has an inverse relationship.

[7] Ceramides induce skeletal muscle insulin resistance when synthesized as a result of saturated fat activation of TLR4 receptors.

[12] In mitochondria, ceramide suppresses the electron transport chain and induces production of reactive oxygen species.

Because of its apoptosis-inducing effects in cancer cells, ceramide has been termed the "tumor suppressor lipid".

[18][19][20] It is composed of terminally differentiated and enucleated corneocytes that reside within a lipid matrix, like "bricks and mortar."

Together with cholesterol and free fatty acids, ceramides form the lipid mortar, a water-impermeable barrier that prevents evaporative water loss.

[18] The diversity of ceramide structures undoubtedly plays an important role in the unique attributes of the stratum corneum across different body sites.

In contrast, the stratum corneum covering the heel of the foot is thick and rigid to protect against trauma.

[citation needed] Ceramide has also been shown to form organized large channels traversing the mitochondrial outer membrane.

[33][34][35] 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).