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

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-,...

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Published inBiochimica 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
LanguageEnglish
Published Netherlands Elsevier B.V 01.09.2012
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Abstract 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.
AbstractList 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.
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.
Author Siponen, Marina I.
Alexson, Stefan E.H.
Hunt, Mary C.
Author_xml – sequence: 1
  givenname: Mary C.
  surname: Hunt
  fullname: Hunt, Mary C.
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– sequence: 2
  givenname: Marina I.
  surname: Siponen
  fullname: Siponen, Marina I.
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  givenname: Stefan E.H.
  surname: Alexson
  fullname: Alexson, Stefan E.H.
  organization: Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Chemistry, Karolinska University Hospital at Huddinge, SE-141 86 Stockholm, Sweden
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Issue 9
Keywords 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
Language English
License http://www.elsevier.com/open-access/userlicense/1.0
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Snippet The importance of peroxisomes in lipid metabolism is now well established and peroxisomes contain approximately 60 enzymes involved in these lipid metabolic...
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SubjectTerms 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
Title The emerging role of acyl-CoA thioesterases and acyltransferases in regulating peroxisomal lipid metabolism
URI https://dx.doi.org/10.1016/j.bbadis.2012.03.009
https://www.ncbi.nlm.nih.gov/pubmed/22465940
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Volume 1822
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