Identification of bile acid-CoA:amino acid N-acyltransferase as the hepatic N-acyl taurine synthase for polyunsaturated fatty acids
N-acyl taurines (NATs) are bioactive lipids with emerging roles in glucose homeostasis and lipid metabolism. The acyl chains of hepatic and biliary NATs are enriched in polyunsaturated fatty acids (PUFAs). Dietary supplementation with a class of PUFAs, the omega-3 fatty acids, increases their cognat...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227523000342 |
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| author | Samuel A.J. Trammell Luke F. Gamon Kamil Gotfryd Katja Thorøe Michler Bandar D. Alrehaili Iben Rix Filip K. Knop Pontus Gourdon Yoon-Kwang Lee Michael J. Davies Matthew P. Gillum Trisha J. Grevengoed |
| author_facet | Samuel A.J. Trammell Luke F. Gamon Kamil Gotfryd Katja Thorøe Michler Bandar D. Alrehaili Iben Rix Filip K. Knop Pontus Gourdon Yoon-Kwang Lee Michael J. Davies Matthew P. Gillum Trisha J. Grevengoed |
| author_sort | Samuel A.J. Trammell |
| collection | DOAJ |
| description | N-acyl taurines (NATs) are bioactive lipids with emerging roles in glucose homeostasis and lipid metabolism. The acyl chains of hepatic and biliary NATs are enriched in polyunsaturated fatty acids (PUFAs). Dietary supplementation with a class of PUFAs, the omega-3 fatty acids, increases their cognate NATs in mice and humans. However, the synthesis pathway of the PUFA-containing NATs remains undiscovered. Here, we report that human livers synthesize NATs and that the acyl-chain preference is similar in murine liver homogenates. In the mouse, we found that hepatic NAT synthase activity localizes to the peroxisome and depends upon an active-site cysteine. Using unbiased metabolomics and proteomics, we identified bile acid-CoA:amino acid N-acyltransferase (BAAT) as the likely hepatic NAT synthase in vitro. Subsequently, we confirmed that BAAT knockout livers lack up to 90% of NAT synthase activity and that biliary PUFA-containing NATs are significantly reduced compared with wildtype. In conclusion, we identified the in vivo PUFA-NAT synthase in the murine liver and expanded the known substrates of the bile acid-conjugating enzyme, BAAT, beyond classic bile acids to the synthesis of a novel class of bioactive lipids. |
| first_indexed | 2024-03-11T22:33:29Z |
| format | Article |
| id | doaj.art-f84f1e3b40024fd5a3352b3eef7e65dc |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-03-11T22:33:29Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-f84f1e3b40024fd5a3352b3eef7e65dc2023-09-23T05:09:45ZengElsevierJournal of Lipid Research0022-22752023-09-01649100361Identification of bile acid-CoA:amino acid N-acyltransferase as the hepatic N-acyl taurine synthase for polyunsaturated fatty acidsSamuel A.J. Trammell0Luke F. Gamon1Kamil Gotfryd2Katja Thorøe Michler3Bandar D. Alrehaili4Iben Rix5Filip K. Knop6Pontus Gourdon7Yoon-Kwang Lee8Michael J. Davies9Matthew P. Gillum10Trisha J. Grevengoed11Department of Biomedical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA; Department of Pharmacology and Toxicology, Pharmacy College, Taibah University, Medina, Saudi ArabiaCenter for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, DenmarkCenter for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Steno Diabetes Center Copenhagen, Herlev, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Experimental Medical Science, Lund University, Lund, SwedenDepartment of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH, USADepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, DenmarkGlobal Obesity and Liver Disease Research, Novo Nordisk A/S, Måløv, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark; For correspondence: Trisha J. GrevengoedN-acyl taurines (NATs) are bioactive lipids with emerging roles in glucose homeostasis and lipid metabolism. The acyl chains of hepatic and biliary NATs are enriched in polyunsaturated fatty acids (PUFAs). Dietary supplementation with a class of PUFAs, the omega-3 fatty acids, increases their cognate NATs in mice and humans. However, the synthesis pathway of the PUFA-containing NATs remains undiscovered. Here, we report that human livers synthesize NATs and that the acyl-chain preference is similar in murine liver homogenates. In the mouse, we found that hepatic NAT synthase activity localizes to the peroxisome and depends upon an active-site cysteine. Using unbiased metabolomics and proteomics, we identified bile acid-CoA:amino acid N-acyltransferase (BAAT) as the likely hepatic NAT synthase in vitro. Subsequently, we confirmed that BAAT knockout livers lack up to 90% of NAT synthase activity and that biliary PUFA-containing NATs are significantly reduced compared with wildtype. In conclusion, we identified the in vivo PUFA-NAT synthase in the murine liver and expanded the known substrates of the bile acid-conjugating enzyme, BAAT, beyond classic bile acids to the synthesis of a novel class of bioactive lipids.http://www.sciencedirect.com/science/article/pii/S0022227523000342bile acids and salts/biosynthesisbile acids and salts/metabolismliveromega-3 fatty acidsperoxisomes |
| spellingShingle | Samuel A.J. Trammell Luke F. Gamon Kamil Gotfryd Katja Thorøe Michler Bandar D. Alrehaili Iben Rix Filip K. Knop Pontus Gourdon Yoon-Kwang Lee Michael J. Davies Matthew P. Gillum Trisha J. Grevengoed Identification of bile acid-CoA:amino acid N-acyltransferase as the hepatic N-acyl taurine synthase for polyunsaturated fatty acids Journal of Lipid Research bile acids and salts/biosynthesis bile acids and salts/metabolism liver omega-3 fatty acids peroxisomes |
| title | Identification of bile acid-CoA:amino acid N-acyltransferase as the hepatic N-acyl taurine synthase for polyunsaturated fatty acids |
| title_full | Identification of bile acid-CoA:amino acid N-acyltransferase as the hepatic N-acyl taurine synthase for polyunsaturated fatty acids |
| title_fullStr | Identification of bile acid-CoA:amino acid N-acyltransferase as the hepatic N-acyl taurine synthase for polyunsaturated fatty acids |
| title_full_unstemmed | Identification of bile acid-CoA:amino acid N-acyltransferase as the hepatic N-acyl taurine synthase for polyunsaturated fatty acids |
| title_short | Identification of bile acid-CoA:amino acid N-acyltransferase as the hepatic N-acyl taurine synthase for polyunsaturated fatty acids |
| title_sort | identification of bile acid coa amino acid n acyltransferase as the hepatic n acyl taurine synthase for polyunsaturated fatty acids |
| topic | bile acids and salts/biosynthesis bile acids and salts/metabolism liver omega-3 fatty acids peroxisomes |
| url | http://www.sciencedirect.com/science/article/pii/S0022227523000342 |
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