The emerging role of acyl-CoA thioesterases and acyltransferases in regulating peroxisomal lipid metabolism

• Published in: Biochimica et biophysica acta Vol. 1822; no. 9; pp. 1397 - 1410
• Main Authors: Hunt, Mary C., Siponen, Marina I., Alexson, Stefan E.H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2012
• Subjects: Acyl Coenzyme A - metabolism; Acyl-CoA thioesterase; Acyltransferases - genetics; Acyltransferases - metabolism; Acyltransferases - physiology; Animals; Bile acid-CoA:amino acid N-acyltransferase; Bile Acids and Salts - metabolism; Cholic Acids - blood; Cholic Acids - genetics; Coenzyme A; Humans; Hydrolysis; Lipid Metabolism; Medicin och hälsovetenskap; Models, Molecular; N-Acyl taurine; Palmitoyl-CoA Hydrolase - chemistry; Palmitoyl-CoA Hydrolase - metabolism; Palmitoyl-CoA Hydrolase - physiology; Peroxisome; Peroxisomes - enzymology; Peroxisomes - metabolism; Protein Conformation; Protein structure; Steroid Metabolism, Inborn Errors - enzymology; Steroid Metabolism, Inborn Errors - genetics; CDCA; DMN-CoA; NAT; FXR; FAAH; HNF-4α; PTS1; CoASH; N-Acyl taurine; ACNAT; BAAT; 4-HNE; PPAR; Acyl-CoA thioesterase; Peroxisome; ACOT; Coenzyme A; HAO1; Bile acid-CoA:amino acid N-acyltransferase; ACOX3; Protein structure; CA
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2012.03.009

The importance of peroxisomes in lipid metabolism is now well established and peroxisomes contain approximately 60 enzymes involved in these lipid metabolic pathways. Several acyl-CoA thioesterase enzymes (ACOTs) have been identified in peroxisomes that catalyze the hydrolysis of acyl-CoAs (short-, medium-, long- and very long-chain), bile acid-CoAs, and methyl branched-CoAs, to the free fatty acid and coenzyme A. A number of acyltransferase enzymes, which are structurally and functionally related to ACOTs, have also been identified in peroxisomes, which conjugate (or amidate) bile acid-CoAs and acyl-CoAs to amino acids, resulting in the production of amidated bile acids and fatty acids. The function of ACOTs is to act as auxiliary enzymes in the α- and β-oxidation of various lipids in peroxisomes. Human peroxisomes contain at least two ACOTs (ACOT4 and ACOT8) whereas mouse peroxisomes contain six ACOTs (ACOT3, 4, 5, 6, 8 and 12). Similarly, human peroxisomes contain one bile acid-CoA:amino acid N-acyltransferase (BAAT), whereas mouse peroxisomes contain three acyltransferases (BAAT and acyl-CoA:amino acid N-acyltransferases 1 and 2: ACNAT1 and ACNAT2). This review will focus on the human and mouse peroxisomal ACOT and acyltransferase enzymes identified to date and discuss their cellular localizations, emerging structural information and functions as auxiliary enzymes in peroxisomal metabolic pathways. This article is part of a Special Issue entitled: Metabolic Functions and Biogenesis of Peroxisomes in Health and Disease. ► ACOTs regulate acyl-CoA metabolism in peroxisomes. ► Peroxisomes produce glycine and taurine-conjugated fatty acids. ► BAAT is involved in the inheritance of familial hypercholanemia. ► New insights into acyl-CoA thioesterase structure and function. ► ACOTs structurally belong to the α/β hydrolase and HotDog fold protein superfamilies.