1-Deoxysphingolipids Encountered Exogenously and Made De Novo: Dangerous Mysteries inside an Enigma [Metabolism]

May 6th, 2015 by Duan, J., Merrill, A. H.

The traditional backbones of mammalian sphingolipids are 2-amino, 1, 3-diols made by serine palmitoyltransferase (SPT). Many organisms additionally produce non-traditional, cytotoxic 1-deoxysphingoid bases and, surprisingly, mammalian SPT biosynthesizes some of them, too (e.g., 1-deoxysphinganine from L-alanine). These are rapidly N-acylated to 1-deoxy-″ceramides″ with very uncommon biophysical properties. The functions of 1-deoxysphingolipids are not known, but they are certainly dangerous as contributors to sensory and autonomic neuropathies when elevated by inherited SPT mutations, and they are noticable in diabetes, non-alcoholic steatohepatitis, serine deficiencies and other disease. As components of food as well as made endogenously, these are new mysteries within an enigma.