Molecular cloning and characterization of two mouse peroxisome proliferator-activated receptor alpha (PPARalpha)-regulated peroxisomal acyl-CoA thioesterases

J Biol Chem. 2004 May 21;279(21):21841-8. doi: 10.1074/jbc.M313863200. Epub 2004 Mar 8.


Peroxisomes are organelles that function in the beta-oxidation of long- and very long-chain acyl-CoAs, bile acid-CoA intermediates, prostaglandins, leukotrienes, thromboxanes, dicarboxylic fatty acids, pristanic acid, and xenobiotic carboxylic acids. The very long- and long-chain acyl-CoAs are mainly chain-shortened and then transported to mitochondria for further metabolism. We have now identified and characterized two peroxisomal acyl-CoA thioesterases, named PTE-Ia and PTE-Ic, that hydrolyze acyl-CoAs to the free fatty acid and coenzyme A. PTE-Ia and PTE-Ic show 82% sequence identity at the amino acid level, and a putative peroxisomal type 1 targeting signal of -AKL was identified at the carboxyl-terminal end of both proteins. Localization experiments using green fluorescent fusion protein showed PTE-Ia and PTE-Ic to be localized in peroxisomes. Despite their high level of sequence identity, we show that PTE-Ia is mainly active on long-chain acyl-CoAs, whereas PTE-Ic is mainly active on medium-chain acyl-CoAs. Lack of regulation of enzyme activity by free CoASH suggests that PTE-Ia and PTE-Ic regulate intraperoxisomal levels of acyl-CoA, and they may have a function in termination of beta-oxidation of fatty acids of different chain lengths. Tissue expression studies revealed that PTE-Ia is highly expressed in kidney, whereas PTE-Ic is most highly expressed in spleen, brain, testis, and proximal and distal intestine. Both PTE-Ia and PTE-Ic were highly up-regulated in mouse liver by treatment with the peroxisome proliferator WY-14,643 and by fasting in a peroxisome proliferator-activated receptor alpha-dependent manner. These data show that PTE-Ia and PTE-Ic have different functions based on different substrate specificities and tissue expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Western
  • Cloning, Molecular
  • Cytosol / metabolism
  • DNA, Complementary / metabolism
  • Fibroblasts / metabolism
  • Gene Expression Regulation
  • Green Fluorescent Proteins
  • Humans
  • Hydrolysis
  • Kinetics
  • Liver / metabolism
  • Luminescent Proteins / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Mitochondria / metabolism
  • Models, Genetic
  • Molecular Sequence Data
  • Oxygen / metabolism
  • Peroxisomes / metabolism
  • Protein Structure, Tertiary
  • Pyrimidines / pharmacology
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Skin / metabolism
  • Thiolester Hydrolases / chemistry*
  • Thiolester Hydrolases / metabolism
  • Time Factors
  • Tissue Distribution
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • Transfection
  • Up-Regulation


  • DNA, Complementary
  • Luminescent Proteins
  • Pyrimidines
  • Receptors, Cytoplasmic and Nuclear
  • Recombinant Proteins
  • Transcription Factors
  • Green Fluorescent Proteins
  • pirinixic acid
  • Thiolester Hydrolases
  • CTE-1 protein, mouse
  • Oxygen

Associated data

  • GENBANK/AY563097
  • GENBANK/AY563098
  • GENBANK/AY563099