| Function
Serine palmitoyltransferase (SPT) catalyzes the conversion of palmitoyl-CoA and serine to CoA and dehydro-sphinganine. This reaction is part of sphingosine biosynthesis. Pyridoxal phosphate (PLP) is a cofactor in the reaction. The prokaryotic SPT is a soluble homodimer while the eukaryotic one is heterodimeric and is anchored in the endoplasmic reticulum[1].
- SPT1 is required for sphingolipids synthesis[2].
- SPT2 is the rate-limiting enzyme of ceramide synthesis[3].
Structural highlights
The active site of SPT contains a serine residue covalently bound to the cofactor PLP[4]. Water molecules are shown as red spheres.
- ↑ Hanada K. Serine palmitoyltransferase, a key enzyme of sphingolipid metabolism. Biochim Biophys Acta. 2003 Jun 10;1632(1-3):16-30. PMID:12782147
- ↑ Kuo A, Checa A, Niaudet C, Jung B, Fu Z, Wheelock CE, Singh SA, Aikawa M, Smith LE, Proia RL, Hla T. Murine endothelial serine palmitoyltransferase 1 (SPTLC1) is required for vascular development and systemic sphingolipid homeostasis. Elife. 2022 Oct 5;11:e78861. PMID:36197001 doi:10.7554/eLife.78861
- ↑ Lallement J, Raho I, Merlen G, Rainteau D, Croyal M, Schiffano M, Kassis N, Doignon I, Soty M, Lachkar F, Krempf M, Van Hul M, Cani PD, Foufelle F, Amouyal C, Le Stunff H, Magnan C, Tordjmann T, Cruciani-Guglielmacci C. Hepatic deletion of serine palmitoyl transferase 2 impairs ceramide/sphingomyelin balance, bile acids homeostasis and leads to liver damage in mice. Biochim Biophys Acta Mol Cell Biol Lipids. 2023 Aug;1868(8):159333. PMID:37224999 doi:10.1016/j.bbalip.2023.159333
- ↑ Ikushiro H, Islam MM, Okamoto A, Hoseki J, Murakawa T, Fujii S, Miyahara I, Hayashi H. Structural insights into the enzymatic mechanism of serine palmitoyltransferase from Sphingobacterium multivorum. J Biochem. 2009 Oct;146(4):549-62. Epub 2009 Jun 29. PMID:19564159 doi:10.1093/jb/mvp100
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3D structures of serine palmitoyltransferase
Serine palmitoyltransferase 3D structures
References
