1-Deoxysphinganine (m18:0)

1-Deoxysphinganine is an atypical sphingolipid that lacks the C1-hydroxyl group of canonical sphinganine and is formed when serine palmitoyltransferase condenses palmitoyl-CoA with alanine instead of serine during sphingolipid synthesis. Plasma levels of 1-deoxysphinganine are increased in patients with hereditary sensory and autonomic neuropathy type 1 (HSAN1), an inherited neuropathy associated with serine palmitoyltransferase gene mutations, and in patients with glycogen storage disease type I (GSDI). Deoxysphingolipids, including 1-deoxysphinganine, are not converted to canonical sphingolipids or fatty acids and accumulate in cells, particularly in the mitochondria where 1-deoxysphinganine induces mitochondrial fragmentation and dysfunction. It also accumulates in LLC-PK1 cells and in mouse liver and kidney following application or administration, respectively, of the ceramide synthase inhibitor fumonisin B1 . 1-Deoxysphinganine is neurotoxic to dorsal root ganglion neurons in vitro, decreasing neurite length and inducing neurite contraction when used at a concentration 1 uM. It is cytotoxic to DU145 cells (IC50 = ~2 uM) but stimulates DNA synthesis in Swiss 3T3 cells when used at a concentration of 1 uM.