Biomaterial Database

Identification of bile acid-CoA:amino acid N-acyltransferase as the hepatic N-acyl taurine synthase for polyunsaturated fatty acids. 2023

Samuel A J Trammell, and Luke F Gamon, and Kamil Gotfryd, and Katja Thorøe Michler, and Bandar D Alrehaili, and Iben Rix, and Filip K Knop, and Pontus Gourdon, and Yoon-Kwang Lee, and Michael J Davies, and Matthew P Gillum, and Trisha J Grevengoed

Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.

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.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D005227	Fatty Acids	Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)	Aliphatic Acid,Esterified Fatty Acid,Fatty Acid,Fatty Acids, Esterified,Fatty Acids, Saturated,Saturated Fatty Acid,Aliphatic Acids,Acid, Aliphatic,Acid, Esterified Fatty,Acid, Saturated Fatty,Esterified Fatty Acids,Fatty Acid, Esterified,Fatty Acid, Saturated,Saturated Fatty Acids
D005231	Fatty Acids, Unsaturated	FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds.	Fatty Acids, Polyunsaturated,Polyunsaturated Fatty Acid,Unsaturated Fatty Acid,Polyunsaturated Fatty Acids,Acid, Polyunsaturated Fatty,Acid, Unsaturated Fatty,Acids, Polyunsaturated Fatty,Acids, Unsaturated Fatty,Fatty Acid, Polyunsaturated,Fatty Acid, Unsaturated,Unsaturated Fatty Acids
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000217	Acyltransferases	Enzymes from the transferase class that catalyze the transfer of acyl groups from donor to acceptor, forming either esters or amides. (From Enzyme Nomenclature 1992) EC 2.3.	Acyltransferase
D000596	Amino Acids	Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.	Amino Acid,Acid, Amino,Acids, Amino
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001647	Bile Acids and Salts	Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.	Bile Acid,Bile Salt,Bile Salts,Bile Acids,Acid, Bile,Acids, Bile,Salt, Bile,Salts, Bile
D013654	Taurine	A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids.	Taufon,Tauphon,Taurine Hydrochloride,Taurine Zinc Salt (2:1),Taurine, Monopotassium Salt
D015525	Fatty Acids, Omega-3	A group of unsaturated fatty acids occurring mainly in fish oils, with three double bonds at particular positions in the hydrocarbon chain.	N-3 Fatty Acid,Omega-3 Fatty Acid,Omega-3 Fatty Acids,n-3 Fatty Acids,n-3 Oil,n3 Oil,Omega 3 Fatty Acids,n-3 Oils,n-3 PUFA,n-3 Polyunsaturated Fatty Acid,n3 Fatty Acid,n3 Oils,n3 PUFA,n3 Polyunsaturated Fatty Acid,Acid, N-3 Fatty,Acid, Omega-3 Fatty,Fatty Acid, N-3,Fatty Acid, Omega-3,Fatty Acid, n3,N 3 Fatty Acid,Oil, n-3,Oil, n3,Omega 3 Fatty Acid,PUFA, n-3,PUFA, n3,n 3 Fatty Acids,n 3 Oil,n 3 Oils,n 3 PUFA,n 3 Polyunsaturated Fatty Acid