[HTML][HTML] Hereditary Sensory Neuropathy Type 1 Is Caused by the Accumulation of Two Neurotoxic Sphingolipids*♦
A Penno, MM Reilly, H Houlden, M Laurá… - Journal of biological …, 2010 - ASBMB
HSAN1 is an inherited neuropathy found to be associated with several missense mutations
in the SPTLC1 subunit of serine palmitoyltransferase (SPT). SPT catalyzes the condensation
of serine and palmitoyl-CoA, the initial step in the de novo synthesis of sphingolipids. Here
we show that the HSAN1 mutations induce a shift in the substrate specificity of SPT, which
leads to the formation of the two atypical deoxy-sphingoid bases (DSBs) 1-deoxy-
sphinganine and 1-deoxymethyl-sphinganine. Both metabolites lack the C 1 hydroxyl group …
in the SPTLC1 subunit of serine palmitoyltransferase (SPT). SPT catalyzes the condensation
of serine and palmitoyl-CoA, the initial step in the de novo synthesis of sphingolipids. Here
we show that the HSAN1 mutations induce a shift in the substrate specificity of SPT, which
leads to the formation of the two atypical deoxy-sphingoid bases (DSBs) 1-deoxy-
sphinganine and 1-deoxymethyl-sphinganine. Both metabolites lack the C 1 hydroxyl group …