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.¹ 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).^2,3 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.⁴ 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 (Item No. 62580).¹ 1-Deoxysphinganine is neurotoxic to dorsal root ganglion neurons in vitro, decreasing neurite length and inducing neurite contraction when used at a concentration 1 µM.² It is cytotoxic to DU145 cells (IC₅₀ = ~2 µM) but stimulates DNA synthesis in Swiss 3T3 cells when used at a concentration of 1 µM.^1,5

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1. Zitomer, N.C., Mitchell, T., Voss, K.A., et al. Ceramide synthase inhibition by fumonisin B₁ causes accumulation of 1-deoxysphinganine. A novel category of bioactive 1-deoxysphingoid bases and 1-deoxydihydroceramides biosynthesized by mammalian cell lines and animals. The Journal of Biological Chemisty 284(8), 4786-4795 (2009).

2. Penno, A., Reilly, M.M., Houlden, H., et al. Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids. The Journal of Biological Chemisty 285(15), 11178-11187 (2010).

3. Hornemann, T., Alecu, I., Hagenbuch, N., et al. Disturbed sphingolipid metabolism with elevated 1-deoxysphingolipids in glycogen storage disease type I - A link to metabolic control. Mol. Genet. Metab. 125(1-2), 73-78 (2018).

4. Alecu, I., Tedeschi, A., Behler, N., et al. Localization of 1-deoxysphingolipids to mitochondria induces mitochondrial dysfunction. J. Lipid. Res. 58(1), 42-59 (2017).

5. Schroeder, J.J., Crane, H.M., Xia, J., et al. Disruption of sphingolipid metabolism and stimulation of DNA synthesis by fumonisin B₁. A molecular mechanism for carcinogenesis associated with Fusarium moniliforme. The Journal of Biological Chemisty 269(5), 3475-3481 (1994).