Dihydroceramide

Dihydroceramide is a type of sphingolipid that consists of a ceramide with a saturated sphingoid base. Chemically, it is N-acyl-sphinganine linked to a fatty acid by an amide bond, and it lacks the double bond between carbon atoms 4 and 5 found in ceramide’s sphingosine backbone.

Biosynthesis and metabolism occur in the de novo sphingolipid pathway. Serine palmitoyltransferase initially forms 3-ketosphinganine, which is reduced to dihydrosphingosine. This dihydrosphingosine is then N-acylated by ceramide synthases to produce dihydroceramide. Dihydroceramide desaturase (DEGS1/DEGS2) introduces the double bond to form ceramide, linking dihydroceramide as a key precursor in sphingolipid metabolism.

Occurrence and distribution are broad in mammalian tissues and fluids. Dihydroceramide exists as an intermediate in cells with active sphingolipid turnover and is present in plasma and other biological samples. It can also be found within the complex lipid matrix of the skin’s stratum corneum as part of barrier lipids.

Biological roles are increasingly recognized as more than merely a step in ceramide production. Dihydroceramide is involved in signaling pathways that influence autophagy and apoptosis and can affect membrane properties used by cells in signaling and trafficking. Because it lies directly upstream of ceramide, its levels reflect flux through the sphingolipid pathway and ARE often used as a readout of desaturation activity.

Clinical and research notes: Altered dihydroceramide metabolism has been studied in relation to metabolic, neurodegenerative, and inflammatory contexts. Lipidomics methods commonly quantify dihydroceramide alongside ceramide species to investigate sphingolipid pathway dynamics.