Serine Palmitoyltransferase Subunit 3 and Metabolic Diseases.
Metabolic diseases
Serine palmitoyltransferase
Serine palmitoyltransferase subunit 3 (Sptlc3)
Sphingolipid biosynthesis
Sphingolipids
Journal
Advances in experimental medicine and biology
ISSN: 0065-2598
Titre abrégé: Adv Exp Med Biol
Pays: United States
ID NLM: 0121103
Informations de publication
Date de publication:
2022
2022
Historique:
entrez:
3
5
2022
pubmed:
4
5
2022
medline:
6
5
2022
Statut:
ppublish
Résumé
Sphingolipids (SL) are a class of chemically diverse lipids that have important structural and physiological functions in eukaryotic cells. SL entail a long chain base (LCB) as the common structural element, which is typically formed by the condensation of L-serine and long chain acyl-CoA. This condensation is the first and the rate-limiting step in the de novo SL synthesis and catalyzed by the enzyme serine palmitoyltransferase (SPT). Although palmitoyl-CoA is the preferred substrate, SPT can also metabolize other acyl-CoAs, thereby forming a variety of LCBs, which differ in structures and functions. The mammalian SPT enzyme is composed of three core subunits: SPTLC1, SPTLC2, and SPTLC3. Whereas SPTLC1 and SPTLC2 are ubiquitously expressed, SPTLC3 expression is restricted to a few specific tissues. The SPTLC1 subunit is essential and can associate with either SPTLC2 or SPTLC3 to form an active enzyme. Depending on the stoichiometry of the SPTLC2 and SPTLC3 subunits, the spectrum of SPT products varies. While SPTLC1 and SPTLC2 primarily form C
Identifiants
pubmed: 35503173
doi: 10.1007/978-981-19-0394-6_4
doi:
Substances chimiques
Sphingolipids
0
Serine
452VLY9402
Serine C-Palmitoyltransferase
EC 2.3.1.50
Coenzyme A
SAA04E81UX
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
47-56Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd.
Références
Harrison, P. J., Dunn, T. M., & Campopiano, D. J. (2018). Sphingolipid biosynthesis in man and microbes. Natural Product Reports, 35(9), 921–954.
pubmed: 29863195
pmcid: 6148460
doi: 10.1039/C8NP00019K
Carreira, A. C., et al. (2019). Mammalian sphingoid bases: Biophysical, physiological and pathological properties. Progress in Lipid Research, 75, 100988.
pubmed: 31132366
doi: 10.1016/j.plipres.2019.100988
Pruett, S. T., et al. (2008). Biodiversity of sphingoid bases (“sphingosines”) and related amino alcohols. Journal of Lipid Research, 49(8), 1621–1639.
pubmed: 18499644
pmcid: 2444003
doi: 10.1194/jlr.R800012-JLR200
Fyrst, H., Herr, D. R., Harris, G. L., & Saba, J. D. (2004). Characterization of free endogenous C14 and C16 sphingoid bases from Drosophila melanogaster. Journal of Lipid Research, 45(1), 54–62.
pubmed: 13130120
doi: 10.1194/jlr.M300005-JLR200
Hannich, J. T., Mellal, D., Feng, S., Zumbuehl, A., & Riezman, H. (2017). Structure and conserved function of iso-branched sphingoid bases from the nematode Caenorhabditis elegans. Chemical Science, 8(5), 3676–3686.
pubmed: 30155209
pmcid: 6094178
doi: 10.1039/C6SC04831E
Lone, M. A., Santos, T., Alecu, I., Silva, L. C., & Hornemann, T. (2019). 1-Deoxysphingolipids. Biochimica et Biophysica Acta—Molecular and Cell Biology of Lipids, 1864(4), 512–521.
pubmed: 30625374
doi: 10.1016/j.bbalip.2018.12.013
Wang, Y., et al. (2021). Structural insights into the regulation of human serine palmitoyltransferase complexes. Nature Structural & Molecular Biology, 28(3), 240–248.
doi: 10.1038/s41594-020-00551-9
Li, S., Xie, T., Liu, P., Wang, L., & Gong, X. (2021). Structural insights into the assembly and substrate selectivity of human SPT–ORMDL3 complex. Nature Structural & Molecular Biology, 28(3), 249–257.
doi: 10.1038/s41594-020-00553-7
Lone, M. A., et al. (2020). Subunit composition of the mammalian serine-palmitoyltransferase defines the spectrum of straight and methyl-branched long-chain bases. Proceedings of the National Academy of Sciences of the United States of America, 117(27), 15591–15598.
pubmed: 32576697
pmcid: 7355037
doi: 10.1073/pnas.2002391117
Davis, D., Kannan, M., & Wattenberg, B. (2018). Orm/ORMDL proteins: Gate guardians and master regulators. Advances in Biological Regulation, 70, 3–18.
pubmed: 30193828
pmcid: 6251742
doi: 10.1016/j.jbior.2018.08.002
Han, G., et al. (2009). Identification of small subunits of mammalian serine palmitoyltransferase that confer distinct acyl-CoA substrate specificities. Proceedings of the National Academy of Sciences of the United States of America, 106(20), 8186–8191.
pubmed: 19416851
pmcid: 2688822
doi: 10.1073/pnas.0811269106
Zhao, L., et al. (2015). Elevation of 20-carbon long chain bases due to a mutation in serine palmitoyltransferase small subunit b results in neurodegeneration. Proceedings of the National Academy of Sciences of the United States of America, 112(42), 12962–12967.
pubmed: 26438849
pmcid: 4620873
doi: 10.1073/pnas.1516733112
Hornemann, T., Richard, S., Rutti, M. F., Wei, Y., & von Eckardstein, A. (2006). Cloning and initial characterization of a new subunit for mammalian serine-palmitoyltransferase. The Journal of Biological Chemistry, 281(49), 37275–37281.
pubmed: 17023427
doi: 10.1074/jbc.M608066200
Ikushiro, H., Hayashi, H., & Kagamiyama, H. (2001). A water-soluble homodimeric serine palmitoyltransferase from Sphingomonas paucimobilis EY2395T strain. Purification, characterization, cloning, and overproduction. The Journal of Biological Chemistry, 276(21), 18249–18256.
pubmed: 11279212
doi: 10.1074/jbc.M101550200
Teng, C., et al. (2008). Serine palmitoyltransferase, a key enzyme for de novo synthesis of sphingolipids, is essential for male gametophyte development in Arabidopsis. Plant Physiology, 146(3), 1322–1332.
pubmed: 18218968
pmcid: 2259075
doi: 10.1104/pp.107.113506
Dietrich, C. R., et al. (2008). Loss-of-function mutations and inducible RNAi suppression of Arabidopsis LCB2 genes reveal the critical role of sphingolipids in gametophytic and sporophytic cell viability. The Plant Journal, 54(2), 284–298.
pubmed: 18208516
doi: 10.1111/j.1365-313X.2008.03420.x
Harmon, J. M., et al. (2013). Topological and functional characterization of the ssSPTs, small activating subunits of serine palmitoyltransferase. The Journal of Biological Chemistry, 288(14), 10144–10153.
pubmed: 23426370
pmcid: 3617257
doi: 10.1074/jbc.M113.451526
Kimberlin, A. N., et al. (2013). Arabidopsis 56-amino acid serine palmitoyltransferase-interacting proteins stimulate sphingolipid synthesis, are essential, and affect mycotoxin sensitivity. Plant Cell, 25(11), 4627–4639.
pubmed: 24214397
pmcid: 3875740
doi: 10.1105/tpc.113.116145
Lee, S. Y., et al. (2012). Cardiomyocyte specific deficiency of serine palmitoyltransferase subunit 2 reduces ceramide but leads to cardiac dysfunction. The Journal of Biological Chemistry, 287(22), 18429–18439.
pubmed: 22493506
pmcid: 3365730
doi: 10.1074/jbc.M111.296947
Lynch, C. J., & Adams, S. H. (2014). Branched-chain amino acids in metabolic signalling and insulin resistance. Nature Reviews. Endocrinology, 10(12), 723–736.
pubmed: 25287287
pmcid: 4424797
doi: 10.1038/nrendo.2014.171
Wallace, M., et al. (2018). Enzyme promiscuity drives branched-chain fatty acid synthesis in adipose tissues. Nature Chemical Biology, 14(11), 1021–1031.
pubmed: 30327559
pmcid: 6245668
doi: 10.1038/s41589-018-0132-2
Al Sazzad, M. A., Yasuda, T., Murata, M., & Slotte, J. P. (2017). The long-chain sphingoid base of ceramides determines their propensity for lateral segregation. Biophysical Journal, 112(5), 976–983.
pubmed: 28297656
pmcid: 5355484
doi: 10.1016/j.bpj.2017.01.016
Troupiotis-Tsailaki, A., et al. (2017). Ligand chain length drives activation of lipid G protein-coupled receptors. Scientific Reports, 7(1), 2020.
pubmed: 28515494
pmcid: 5435731
doi: 10.1038/s41598-017-02104-5
Vutukuri, R., et al. (2020). S1P d20:1, an endogenous modulator of S1P d18:1/S1P2-dependent signaling. The FASEB Journal, 34(3), 3932–3942.
pubmed: 31944406
doi: 10.1096/fj.201902391R
Hicks, A. A., et al. (2009). Genetic determinants of circulating sphingolipid concentrations in European populations. PLoS Genetics, 5(10), e1000672.
pubmed: 19798445
pmcid: 2745562
doi: 10.1371/journal.pgen.1000672
Illig, T., et al. (2010). A genome-wide perspective of genetic variation in human metabolism. Nature Genetics, 42(2), 137–141.
pubmed: 20037589
doi: 10.1038/ng.507
Demirkan, A., et al. (2012). Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations. PLoS Genetics, 8(2), e1002490.
pubmed: 22359512
pmcid: 3280968
doi: 10.1371/journal.pgen.1002490
Willer, C. J., et al. (2013). Discovery and refinement of loci associated with lipid levels. Nature Genetics, 45(11), 1274–1283.
pubmed: 24097068
pmcid: 3838666
doi: 10.1038/ng.2797
Tabassum, R., et al. (2019). Genetic architecture of human plasma lipidome and its link to cardiovascular disease. Nature Communications, 10(1), 4329.
pubmed: 31551469
pmcid: 6760179
doi: 10.1038/s41467-019-11954-8
Cresci, S., et al. (2020). Genetic architecture of circulating very-long-chain (C24:0 and C22:0) ceramide concentrations. Journal of Lipid and Atherosclerosis, 9(1), 172–183.
pubmed: 32489964
pmcid: 7266332
doi: 10.12997/jla.2020.9.1.172
McGurk, K. A., et al. (2021). Heritability and family-based GWAS analyses of the N-acyl ethanolamine and ceramide plasma lipidome. Human Molecular Genetics, 30(6), 500–513.
pubmed: 33437986
pmcid: 8101358
doi: 10.1093/hmg/ddab002
Choi, R. H., Tatum, S. M., Symons, J. D., Summers, S. A., & Holland, W. L. (2021). Ceramides and other sphingolipids as drivers of cardiovascular disease. Nature Reviews. Cardiology, 18(10), 701–711.
pubmed: 33772258
doi: 10.1038/s41569-021-00536-1
Poss, A. M., et al. (2020). Machine learning reveals serum sphingolipids as cholesterol-independent biomarkers of coronary artery disease. The Journal of Clinical Investigation, 130(3), 1363–1376.
pubmed: 31743112
pmcid: 7269567
doi: 10.1172/JCI131838
Hilvo, M., et al. (2020). Development and validation of a ceramide- and phospholipid-based cardiovascular risk estimation score for coronary artery disease patients. European Heart Journal, 41(3), 371–380.
pubmed: 31209498
Russo, S. B., Tidhar, R., Futerman, A. H., & Cowart, L. A. (2013). Myristate-derived d16:0 sphingolipids constitute a cardiac sphingolipid pool with distinct synthetic routes and functional properties. The Journal of Biological Chemistry, 288(19), 13397–13409.
pubmed: 23530041
pmcid: 3650378
doi: 10.1074/jbc.M112.428185
Mirkov, S., Myers, J. L., Ramirez, J., & Liu, W. (2012). SNPs affecting serum metabolomic traits may regulate gene transcription and lipid accumulation in the liver. Metabolism, 61(11), 1523–1527.
pubmed: 22738862
doi: 10.1016/j.metabol.2012.05.004
Gulati, S., Liu, Y., Munkacsi, A. B., Wilcox, L., & Sturley, S. L. (2010). Sterols and sphingolipids: Dynamic duo or partners in crime? Progress in Lipid Research, 49(4), 353–365.
pubmed: 20362613
pmcid: 2938828
doi: 10.1016/j.plipres.2010.03.003
Shah, C., et al. (2008). Protection from high fat diet-induced increase in ceramide in mice lacking plasminogen activator inhibitor 1. The Journal of Biological Chemistry, 283(20), 13538–13548.
pubmed: 18359942
pmcid: 2376236
doi: 10.1074/jbc.M709950200
Cinar, R., et al. (2014). Hepatic cannabinoid-1 receptors mediate diet-induced insulin resistance by increasing de novo synthesis of long-chain ceramides. Hepatology, 59(1), 143–153.
pubmed: 23832510
doi: 10.1002/hep.26606
Yoshimine, Y., et al. (2015). Hepatic expression of the Sptlc3 subunit of serine palmitoyltransferase is associated with the development of hepatocellular carcinoma in a mouse model of nonalcoholic steatohepatitis. Oncology Reports, 33(4), 1657–1666.
pubmed: 25607821
doi: 10.3892/or.2015.3745
Teng, W., et al. (2019). Sulforaphane prevents hepatic insulin resistance by blocking serine palmitoyltransferase 3-mediated ceramide biosynthesis. Nutrients, 11(5), 1185.
pmcid: 6566605
doi: 10.3390/nu11051185
Dong, Y. Q., et al. (2017). Omega-3 PUFA ameliorates hyperhomocysteinemia-induced hepatic steatosis in mice by inhibiting hepatic ceramide synthesis. Acta Pharmacologica Sinica, 38(12), 1601–1610.
pubmed: 28933423
pmcid: 5719150
doi: 10.1038/aps.2017.127
Chew, W. S., et al. (2019). Large-scale lipidomics identifies associations between plasma sphingolipids and T2DM incidence. JCI Insight, 5(13), e126925.
doi: 10.1172/jci.insight.126925
Gantner, M. L., et al. (2019). Serine and lipid metabolism in macular disease and peripheral neuropathy. The New England Journal of Medicine, 381(15), 1422–1433.
pubmed: 31509666
pmcid: 7685488
doi: 10.1056/NEJMoa1815111
Muthusamy, T., et al. (2020). Serine restriction alters sphingolipid diversity to constrain tumour growth. Nature, 586(7831), 790–795.
pubmed: 32788725
pmcid: 7606299
doi: 10.1038/s41586-020-2609-x
Mohassel, P., et al. (2021). Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis. Nature Medicine, 27(7), 1197–1204.
pubmed: 34059824
doi: 10.1038/s41591-021-01346-1
Gonzaga-Jauregui, C., et al. (2015). Exome sequence analysis suggests that genetic burden contributes to phenotypic variability and complex neuropathy. Cell Reports, 12(7), 1169–1183.
pubmed: 26257172
doi: 10.1016/j.celrep.2015.07.023
Waterhouse, A., et al. (2018). SWISS-MODEL: Homology modelling of protein structures and complexes. Nucleic Acids Research, 46(W1), W296–W303.
pubmed: 29788355
pmcid: 6030848
doi: 10.1093/nar/gky427
Bienert, S., et al. (2017). The SWISS-MODEL repository-new features and functionality. Nucleic Acids Research, 45(D1), D313–D319.
pubmed: 27899672
doi: 10.1093/nar/gkw1132
Guex, N., Peitsch, M. C., & Schwede, T. (2009). Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: A historical perspective. Electrophoresis, 30(Suppl 1), S162–S173.
pubmed: 19517507
doi: 10.1002/elps.200900140
Studer, G., et al. (2020). QMEANDisCo-distance constraints applied on model quality estimation. Bioinformatics, 36(6), 1765–1771.
pubmed: 31697312
doi: 10.1093/bioinformatics/btz828
Bertoni, M., Kiefer, F., Biasini, M., Bordoli, L., & Schwede, T. (2017). Modeling protein quaternary structure of homo- and hetero-oligomers beyond binary interactions by homology. Scientific Reports, 7(1), 10480.
pubmed: 28874689
pmcid: 5585393
doi: 10.1038/s41598-017-09654-8