Reactome | SPTLC complexes transfer acyl-CoA onto serine

SPTLC complexes transfer acyl-CoA onto serine

Stable Identifier

R-HSA-428127

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, endoplasmic reticulum membrane

Synonyms

acyl-CoA + serine => 3-ketosphingoid + CoASH + CO2

ReviewStatus

5/5

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SPTLC complexes transfer acyl-CoA onto serine

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SPTLC (serine palmitoyltransferase) enzyme complexes associated with the endoplasmic reticulum membrane catalyze the reaction of acyl-CoA and serine to form a 3-ketosphingoid. Quantitatively, the most common ligand is palmitoyl-CoA (C16), but different isoforms of the complexes have specific activity toward the C12, C14, and C18 species (Han et al., 2009; Suzuki et al., 2022). SPTLC2 and SPTLC3 polypeptides exhibit enzyme activity when either is complexed with SPTLC1. SPTLC1 and 2 are abundant and widely expressed in human tissues, while SPTLC3 is expressed only in a smaller group of tissues and at variable levels. Analyses of complexes from cultured human cells and placenta suggested that the SPTLC heterodimers might associate with larger complexes (Hanada et al., 2000; Weiss and Stoffel, 1997; Hornemann et al. 2006, 2007; reviewed by Ikushiro & Hayashi, 2011; Lowther et al., 2012). Two novel small subunits (SPTSSA and SPTSSB) were identified, both of which enhance SPTLC activity >10-fold when bound to either of the SPTLC heterodimers (Han et al. 2009). Orosomucoid (ORM) proteins, first identified in yeast, associate with and negatively regulate SPTLC activity (Breslow et al. 2010; Han et al. 2010). The three human ORM proteins similarly bind and negatively regulate SPTLC activity (Breslow et al., 2010; reviewed by Davis et al., 2018). In particular, dysregulation of SPT activity by ORML3 appears to be involved with forms of obesity (reviewed by Brown & Spiegel, 2023). In serine deficiency, SPTLC transfers acyl-CoA onto alanine, and the resulting 1-deoxysphingoids ultimately get processed to 1-deoxyceramides (reviewed by Duan & Merrill, 2015).

Literature References

PubMed ID	Title	Journal	Year
21315853	Mechanistic enzymology of serine palmitoyltransferase Hayashi, H, Ikushiro, H	Biochim Biophys Acta	2011
22616865	Structural, mechanistic and regulatory studies of serine palmitoyltransferase Naismith, JH, Campopiano, DJ, Dunn, TM, Lowther, J	Biochem Soc Trans	2012
17023427	Cloning and initial characterization of a new subunit for mammalian serine-palmitoyltransferase Richard, S, Wei, Y, Rutti, MF, Hornemann, T, von Eckardstein, A	J Biol Chem	2006
9363775	Human and murine serine-palmitoyl-CoA transferase--cloning, expression and characterization of the key enzyme in sphingolipid synthesis Stoffel, W, Weiss, B	Eur J Biochem	1997
20212121	Orm1 and Orm2 are conserved endoplasmic reticulum membrane proteins regulating lipid homeostasis and protein quality control Schneiter, R, Chang, A, Han, S, Lone, MA	Proc. Natl. Acad. Sci. U.S.A.	2010
17331073	Is the mammalian serine palmitoyltransferase a high-molecular-mass complex? Wei, Y, Hornemann, T, von Eckardstein, A	Biochem J	2007
20182505	Orm family proteins mediate sphingolipid homeostasis Aebersold, R, Bodenmiller, B, Weissman, JS, Collins, SR, Simons, K, Shevchenko, A, Ejsing, CS, Breslow, DK	Nature	2010
19416851	Identification of small subunits of mammalian serine palmitoyltransferase that confer distinct acyl-CoA substrate specificities Gupta, SD, Harmon, JM, Brown, RH, Eichler, F, Han, G, Niranjanakumari, S, Moitra, P, Gable, K, Dunn, TM	Proc. Natl. Acad. Sci. U.S.A.	2009
10722674	Purification of the serine palmitoyltransferase complex responsible for sphingoid base synthesis by using affinity peptide chromatography techniques Hara, T, Hanada, K, Nishijima, M	J Biol Chem	2000
37003301	ORMDL in metabolic health and disease Brown, RDR, Spiegel, S	Pharmacol Ther	2023
35654151	Whole picture of human stratum corneum ceramides, including the chain-length diversity of long-chain bases Ohno, Y, Kihara, A, Suzuki, M	J Lipid Res	2022
25947379	1-Deoxysphingolipids Encountered Exogenously and Made de Novo: Dangerous Mysteries inside an Enigma Merrill, AH, Duan, J	J Biol Chem	2015
30193828	Orm/ORMDL proteins: Gate guardians and master regulators Kannan, M, Davis, D, Wattenberg, B	Adv Biol Regul	2018