Serine palmitoyltransferase

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 of SPT contains a ^[4]. Water molecules are shown as red spheres.

Dimeric prokaryotic serine palmitoyltransferase complex with serine and cofactor pyridoxal phosphate 3a2b

Drag the structure with the mouse to rotate

3D structures of serine palmitoyltransferase3D structures of serine palmitoyltransferase

Serine palmitoyltransferase 3D structures

ReferencesReferences

↑ 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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

[1] Hanada K. Serine palmitoyltransferase, a key enzyme of sphingolipid metabolism. Biochim Biophys Acta. 2003 Jun 10;1632(1-3):16-30. PMID:12782147

[2] 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

[3] 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

[4] 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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