dihydroceramides

Dihydroceramides are a subset of sphingolipids characterized by a dihydrosphingosine (sphinganine) base that is N-acylated with a fatty acid. They differ from ceramides by the absence of a trans double bond between the C4 and C5 positions of the sphingoid backbone. In cells, dihydroceramides function as intermediates in de novo sphingolipid biosynthesis and can be converted to ceramides by desaturation.

Biosynthesis and interconversion: The pathway begins with serine palmitoyltransferase, which condenses serine with palmitoyl-CoA to yield 3-ketosphinganine, then is reduced to dihydrosphingosine. Dihydroceramide synthases attach various fatty acyl chains to form dihydroceramides. Dihydroceramide desaturase introduces the C4-C5 double bond to produce ceramide. Dihydroceramides can also be diverted to other sphingolipids, and ceramides can be further metabolized by ceramidases to generate sphingoid bases and fatty acids.

Occurrence and analysis: Dihydroceramides are found in mammalian tissues such as liver, skin, and brain, and circulate in plasma and serum as part of complex lipid pools. They are commonly quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Researchers often report dhCer species alongside ceramides, and use the dhCer/Cer ratio as an index of desaturase activity or overall sphingolipid metabolism status.

Biological relevance: Dihydroceramides are increasingly recognized as more than inert precursors. Some studies suggest they can influence cellular processes related to autophagy, ER stress, and apoptosis, and their levels are altered in metabolic disorders such as obesity and insulin resistance. While associations exist, causal roles remain an area of ongoing investigation, and their clinical utility as biomarkers requires further validation.

Nomenclature: The dhCer species are named by the sphingoid base and the N-acyl chain lengths (for example, dhCer d18:0/24:1), reflecting the two lipid components that define each molecule.