The SPTLC3 subunit of serine palmitoyltransferase generates short chain sphingoid bases.

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Hornemann T, Penno A, Rutti MF, Ernst D, Kivrak-Pfiffner F, Rohrer L, von Eckardstein A

The SPTLC3 subunit of serine palmitoyltransferase generates short chain sphingoid bases.

J Biol Chem. 2009 Sep 25;284(39):26322-30. doi: 10.1074/jbc.M109.023192. Epub 2009 Aug 1.

PubMed ID

19648650 [ View in PubMed

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Abstract

The enzyme serine palmitoyltransferase (SPT) catalyzes the rate-limiting step in the de novo synthesis of sphingolipids. Previously the mammalian SPT was described as a heterodimer composed of two subunits, SPTLC1 and SPTLC2. Recently we identified a novel third SPT subunit (SPTLC3). SPTLC3 shows about 68% identity to SPTLC2 and also includes a pyridoxal phosphate consensus motif. Here we report that the overexpression of SPTLC3 in HEK293 cells leads to the formation of two new sphingoid base metabolites, namely C(16)-sphinganine and C(16)-sphingosine. SPTLC3-expressing cells have higher in vitro SPT activities with lauryl- and myristoyl-CoA than SPTLC2-expressing cells, and SPTLC3 mRNA expression levels correlate closely with the C(16)-sphinganine synthesis rates in various human and murine cell lines. Approximately 15% of the total sphingolipids in human plasma contain a C(16) backbone and are found in the high density and low density but not the very low density lipoprotein fraction. In conclusion, we show that the SPTLC3 subunit generates C(16)-sphingoid bases and that sphingolipids with a C(16) backbone constitute a significant proportion of human plasma sphingolipids.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pyridoxal phosphate	Serine palmitoyltransferase 3	Protein	Humans	Unknown	Cofactor	Details