A peroxisomal acyltransferase in mouse identifies a novel pathway for taurine conjugation of fatty acids

Abstract

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.

Phase II Drug Metabolism

“…Amino acid conjugation is the most important route of detoxification, not only for many xenobiotic carboxylic acids but also for endogenous acids. It is known that amino acid conjugation of exogenous carboxylic acids occurs in a two-step process (Reilly et al, 2007). Amino acids conjugation of carboxylic acids is a special form of acetylation and leads to amide bond formation.…”

Endogenous N -acyl taurines regulate skin wound healing

“…A third group of FAAH substrates, the amides of long-chain fatty acids with taurine [N-acyl-taurines (NATs)], has been identified in liver and other rodent tissues (9,10). The NATs may be produced through enzyme-dependent conjugation of fatty acyl-CoA with taurine-catalyzed by the peroxisomal acyltransferase, acyl-CoA amino acid N-acyltransferase-1 (11,12)-and have demonstrated biological activity in several cellular systems (13,14). Their roles in physiology remain unknown, however.…”

Novel functions of acyl-CoA thioesterases and acyltransferases as auxiliary enzymes in peroxisomal lipid metabolism

“…These two ACNAT proteins show approx 55% sequence identity to BAAT, with 95% sequence identity to each other. ACNAT1 and ACNAT2 both contain a consensus peroxisomal targeting signal of -SKL at the carboxyterminal end, which localizes the proteins to peroxisomes [146] (and Reilly et al, unpublished results). Acnat1 mRNA is mainly expressed in liver and kidney in mouse, and characterization of recombinant ACNAT1 protein identified it as a peroxisomal acyltransferase involved in conjugation of mainly very long-chain and longchain fatty acids (C 16 -C 24 ) to taurine, with some very low activity with bile acids [146].…”

“…Interestingly, the ACNATs also contain an active site serine, however this serine is localized in a SerXaaSerXaaGly motif and not in a GlyXaaSerXaaGly motif common to the ACOTs [146]. A mutation in the BAAT protein (and tight junction protein 2) in an Amish population resulted in familial hypercholanemia, which is characterized by elevated serum bile acid concentrations, itching and fat malabsorption [147].…”

“…7), however as stated earlier, the ACNAT gene in human is a pseudogene. These mouse genes encode two novel acyl-CoA:amino acid N-acyltransferases (ACNAT1 and ACNAT2) and one of these enzymes, ACNAT1, was recently characterized [146]. These two ACNAT proteins show approx 55% sequence identity to BAAT, with 95% sequence identity to each other.…”