A peroxisomal acyltransferase in mouse identifies a novel pathway for taurine conjugation of fatty acids.
A wide variety of endogenous carboxylic acids and xenobiotics are conjugated with amino acids, before excretion in urine or bile. The conjugation of carboxylic acids and bile acids with taurine and glycine has been widely characterized, and de novo synthesized bile acids are conjugated to either glycine or taurine in peroxisomes. Peroxisomes are also involved in the oxidation of several other lipid molecules, such as very long chain acyl-CoAs, branched chain acyl-CoAs, and prostaglandins. In this study, we have now identified a novel peroxisomal enzyme called acyl-coenzyme A:amino acid N-acyltransferase (ACNAT1). Recombinantly expressed ACNAT1 acts as an acyltransferase that efficiently conjugates very long-chain and long-chain fatty acids to taurine. The enzyme shows no conjugating activity with glycine, showing that it is a specific taurine conjugator. Acnat1 is mainly expressed in liver and kidney, and the gene is localized in a gene cluster, together with two further acyltransferases, one of which conjugates bile acids to glycine and taurine. In conclusion, these data describe ACNAT1 as a new acyltransferase, involved in taurine conjugation of fatty acids in peroxisomes, identifying a novel pathway for production of N-acyltaurines as signaling molecules or for excretion of fatty acids.
Reilly
Sarah-Jayne
SJ
Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Chemistry C1-74, Karolinska University Hospital at Huddinge, SE-141 86 Stockholm, Sweden.
O'Shea
Ethna M
EM
Andersson
Ulla
U
O'Byrne
James
J
Alexson
Stefan E H
SE
Hunt
Mary C
MC
D000217:Acyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005227:Fatty Acids / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D020675:Peroxisomes / Q000201:enzymology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D021241:Spectrometry, Mass, Electrospray Ionization; D013654:Taurine / Q000378:metabolism*
D017931:DNA Primers; D005227:Fatty Acids; D011994:Recombinant Proteins; D013654:Taurine; D000217:Acyltransferases