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

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*

*Corresponding author af dette arbejde

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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 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.

OriginalsprogEngelsk
Artikelnummer100361
TidsskriftJournal of Lipid Research
Vol/bind64
Udgave nummer9
Antal sider9
ISSN0022-2275
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
J. D. (NNF20SA0064214) and from Lundbeck Foundation fellowship to L. F. G. (R322-2019-2337).

Funding Information:
This work was funded by a Novo Nordisk Foundation award (NNF21OC0067271) to T. J. G. It was also supported by additional grants from the Novo Nordisk Foundation to M.

Publisher Copyright:
© 2023 THE AUTHORS.

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