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Identification of bile acid-CoA:amino acid N-acyltransferase as the hepatic N-acyl taurine synthase for polyunsaturated fatty acids

Trammell, Samuel A.J. ; Gamon, Luke F. ; Gotfryd, Kamil ; Michler, Katja Thorøe ; Alrehaili, Bandar D. ; Rix, Iben ; Knop, Filip K. ; Gourdon, Pontus LU ; Lee, Yoon Kwang and Davies, Michael J. , et al. (2023) In Journal of Lipid Research 64(9).
Abstract

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... (More)

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 acidconjugating enzyme, BAAT, beyond classic bile acids to the synthesis of a novel class of bioactive lipids.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
bile acids and salts/biosynthesis, bile acids and salts/metabolism, liver, omega-3 fatty acids, peroxisomes
in
Journal of Lipid Research
volume
64
issue
9
article number
100361
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • pmid:36958721
  • scopus:85172425856
ISSN
0022-2275
DOI
10.1016/j.jlr.2023.100361
language
English
LU publication?
yes
id
0de3d2ea-fc76-45d8-9592-74c9329071d5
date added to LUP
2023-12-13 15:09:48
date last changed
2025-05-10 20:34:24
@article{0de3d2ea-fc76-45d8-9592-74c9329071d5,
  abstract     = {{<p>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 acidconjugating enzyme, BAAT, beyond classic bile acids to the synthesis of a novel class of bioactive lipids.</p>}},
  author       = {{Trammell, Samuel A.J. and Gamon, Luke F. and Gotfryd, Kamil and Michler, Katja Thorøe and Alrehaili, Bandar D. and Rix, Iben and Knop, Filip K. and Gourdon, Pontus and Lee, Yoon Kwang and Davies, Michael J. and Gillum, Matthew P. and Grevengoed, Trisha J.}},
  issn         = {{0022-2275}},
  keywords     = {{bile acids and salts/biosynthesis; bile acids and salts/metabolism; liver; omega-3 fatty acids; peroxisomes}},
  language     = {{eng}},
  number       = {{9}},
  publisher    = {{American Society for Biochemistry and Molecular Biology}},
  series       = {{Journal of Lipid Research}},
  title        = {{Identification of bile acid-CoA:amino acid N-acyltransferase as the hepatic N-acyl taurine synthase for polyunsaturated fatty acids}},
  url          = {{http://dx.doi.org/10.1016/j.jlr.2023.100361}},
  doi          = {{10.1016/j.jlr.2023.100361}},
  volume       = {{64}},
  year         = {{2023}},
}