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

Creator:

Westin, Maria; Hunt, Mary; Alexson, Stefan;

Institution: Dublin Institute of Technology
Subject Keywords: acyl-CoA thioesterase; acyl-CoA hydrolase; peroxisomes; lipid metabolism; acyl-CoA; b-oxidation.; Biochemistry and molecular biology; Biochemistry; Life Sciences; Molecular Biology;
Region:
Description:

Peroxisomes are organelles that function in the b-oxidation of very-long and
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, which hydrolyze acyl-CoAs to
the free fatty acid and coenzyme A. PTE-Ia and PTE-Ic show 82% sequence
identity at amino acid level and a putative peroxisomal type 1 targeting signal
of –AKL was identified at the carboxy-terminal end of both proteins.
Localization experiments using green fluorescent fusion protein showed PTEIa
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, while 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 intra-peroxisomal levels of acyl-CoA, and they may have a function
in termination of b-oxidation of fatty acids of different chain-lengths. Tissue
expression studies revealed that PTE-Ia is highly expressed in kidney, while
PTE-Ic is most highly expressed in spleen, brain, testis and proximal and
distal intestine. Both PTE-Ia and PTE-Ic were highly upregulated in mouse
liver by treatment with the peroxisome proliferator WY-14,643 and by fasting,
in a peroxisome proliferator-activated receptor alpha (PPARa) dependent
manner. These data show that PTE-Ia and PTE-Ic have different functions
based on different substrate specificities and tissue expression.

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Suggested citation:

Westin, Maria; Hunt, Mary; Alexson, Stefan; . () Molecular cloning and characterization of two mouse peroxisome proliferator-activated receptor alpha (PPARa) regulated peroxisomal acyl-CoA thioesterases. [Online]. Available from: http://publichealthwell.ie/node/637622 [Accessed: 16th September 2019].

  

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