deoxysphingolipid

Deoxysphingolipids are a subset of sphingolipids characterized by the absence of the C1 hydroxyl group on the sphingoid base. They arise when the enzyme serine palmitoyltransferase uses amino acids other than serine, particularly L-alanine, leading to the formation of 1-deoxysphinganine, which can be further acylated to form deoxysphingolipids. Because they lack the C1 hydroxyl, they cannot be converted into the usual ceramide or glycosphingolipid products in the same way as canonical sphingolipids.

Biosynthesis involves the serine palmitoyltransferase reaction. Normally, SPT condenses palmitoyl-CoA with serine to form 3-ketodihydrosphingosine, which is reduced and acylated to ceramide. When alanine is used instead of serine, 1-deoxysphinganine is produced and subsequently converted into deoxysphingolipids. The missing C1 hydroxyl alters their metabolism and prevents formation of standard complex sphingolipids, affecting their degradability and biological behavior.

Clinical relevance includes elevated levels of deoxysphingolipids in hereditary sensory and autonomic neuropathy type I (HSAN1), linked to mutations in SPTLC1/2 that promote alanine misincorporation. They are also found at higher levels in metabolic diseases such as obesity and type 2 diabetes, and are studied for their potential contribution to neurotoxicity and metabolic dysfunction.

Detection typically relies on mass spectrometry of plasma or serum samples. Research on deoxysphingolipids focuses on their role as biomarkers for sphingolipid metabolism disorders and their contribution to neuropathic and metabolic pathology.