Document Detail

Intrinsic acyl-CoA thioesterase activity of a peroxisomal ATP binding cassette transporter is required for transport and metabolism of fatty acids.
MedLine Citation:
PMID:  23288899     Owner:  NLM     Status:  MEDLINE    
Peroxisomes are organelles that perform diverse metabolic functions in different organisms, but a common function is β-oxidation of a variety of long chain aliphatic, branched, and aromatic carboxylic acids. Import of substrates into peroxisomes for β-oxidation is mediated by ATP binding cassette (ABC) transporter proteins of subfamily D, which includes the human adrenoleukodystropy protein (ALDP) defective in X-linked adrenoleukodystrophy (X-ALD). Whether substrates are transported as CoA esters or free acids has been a matter of debate. Using COMATOSE (CTS), a plant representative of the ABCD family, we demonstrate that there is a functional and physical interaction between the ABC transporter and the peroxisomal long chain acyl-CoA synthetases (LACS)6 and -7. We expressed recombinant CTS in insect cells and showed that membranes from infected cells possess fatty acyl-CoA thioesterase activity, which is stimulated by ATP. A mutant, in which Serine 810 is replaced by asparagine (S810N) is defective in fatty acid degradation in vivo, retains ATPase activity but has strongly reduced thioesterase activity, providing strong evidence for the biological relevance of this activity. Thus, CTS, and most likely the other ABCD family members, represent rare examples of polytopic membrane proteins with an intrinsic additional enzymatic function that may regulate the entry of substrates into the β-oxidation pathway. The cleavage of CoA raises questions about the side of the membrane where this occurs and this is discussed in the context of the peroxisomal coenzyme A (CoA) budget.
Carine De Marcos Lousa; Carlo W T van Roermund; Vincent L G Postis; Daniela Dietrich; Ian D Kerr; Ronald J A Wanders; Stephen A Baldwin; Alison Baker; Frederica L Theodoulou
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-03
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  110     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-23     Completed Date:  2013-03-21     Revised Date:  2014-10-28    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1279-84     Citation Subset:  IM    
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MeSH Terms
ATP-Binding Cassette Transporters / genetics,  metabolism*
Acyl Coenzyme A / metabolism
Amino Acid Substitution
Arabidopsis / genetics,  metabolism
Arabidopsis Proteins / genetics,  metabolism
Biological Transport, Active
Coenzyme A Ligases / metabolism
Fatty Acid Transport Proteins / genetics,  metabolism*
Fatty Acids / metabolism*
Models, Biological
Mutagenesis, Site-Directed
Peroxisomes / metabolism
Plants, Genetically Modified
Recombinant Proteins / genetics,  metabolism
Saccharomyces cerevisiae / genetics,  metabolism
Saccharomyces cerevisiae Proteins / metabolism
Thiolester Hydrolases / genetics,  metabolism*
Grant Support
BB/F007108/1//Biotechnology and Biological Sciences Research Council; BB/F007299/1//Biotechnology and Biological Sciences Research Council
Reg. No./Substance:
0/Acyl Coenzyme A; 0/Arabidopsis Proteins; 0/Fatty Acid Transport Proteins; 0/Fatty Acids; 0/Ped3 protein, Arabidopsis; 0/Recombinant Proteins; 0/Saccharomyces cerevisiae Proteins; EC 3.1.2.-/Thiolester Hydrolases; EC 6.2.1.-/Coenzyme A Ligases; EC protein, S cerevisiae; EC protein, Arabidopsis; EC protein, Arabidopsis

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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