Linked Life Data

11673457

Source:http://linkedlifedata.com/resource/pubmed/id/11673457

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-1-7
pubmed:databankReference
pubmed:abstractText
Peroxisomes function in beta-oxidation of very long and long-chain fatty acids, dicarboxylic fatty acids, bile acid intermediates, prostaglandins, leukotrienes, thromboxanes, pristanic acid, and xenobiotic carboxylic acids. These lipids are mainly chain-shortened for excretion as the carboxylic acids or transported to mitochondria for further metabolism. Several of these carboxylic acids are slowly oxidized and may therefore sequester coenzyme A (CoASH). To prevent CoASH sequestration and to facilitate excretion of chain-shortened carboxylic acids, acyl-CoA thioesterases, which catalyze the hydrolysis of acyl-CoAs to the free acid and CoASH, may play important roles. Here we have cloned and characterized a peroxisomal acyl-CoA thioesterase from mouse, named PTE-2 (peroxisomal acyl-CoA thioesterase 2). PTE-2 is ubiquitously expressed and induced at mRNA level by treatment with the peroxisome proliferator WY-14,643 and fasting. Induction seen by these treatments was dependent on the peroxisome proliferator-activated receptor alpha. Recombinant PTE-2 showed a broad chain length specificity with acyl-CoAs from short- and medium-, to long-chain acyl-CoAs, and other substrates including trihydroxycoprostanoyl-CoA, hydroxymethylglutaryl-CoA, and branched chain acyl-CoAs, all of which are present in peroxisomes. Highest activities were found with the CoA esters of primary bile acids choloyl-CoA and chenodeoxycholoyl-CoA as substrates. PTE-2 activity is inhibited by free CoASH, suggesting that intraperoxisomal free CoASH levels regulate the activity of this enzyme. The acyl-CoA specificity of recombinant PTE-2 closely resembles that of purified mouse liver peroxisomes, suggesting that PTE-2 is the major acyl-CoA thioesterase in peroxisomes. Addition of recombinant PTE-2 to incubations containing isolated mouse liver peroxisomes strongly inhibited bile acid-CoA:amino acid N-acyltransferase activity, suggesting that this thioesterase can interfere with CoASH-dependent pathways. We propose that PTE-2 functions as a key regulator of peroxisomal lipid metabolism.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1128-38
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11673457-Acyl Coenzyme A, pubmed-meshheading:11673457-Amino Acid Sequence, pubmed-meshheading:11673457-Animals, pubmed-meshheading:11673457-Cloning, Molecular, pubmed-meshheading:11673457-Coenzyme A, pubmed-meshheading:11673457-Enzyme Induction, pubmed-meshheading:11673457-Fibroblasts, pubmed-meshheading:11673457-Genes, Reporter, pubmed-meshheading:11673457-Humans, pubmed-meshheading:11673457-Lipid Metabolism, pubmed-meshheading:11673457-Liver, pubmed-meshheading:11673457-Male, pubmed-meshheading:11673457-Mice, pubmed-meshheading:11673457-Mice, Inbred C57BL, pubmed-meshheading:11673457-Microscopy, Fluorescence, pubmed-meshheading:11673457-Models, Biological, pubmed-meshheading:11673457-Molecular Sequence Data, pubmed-meshheading:11673457-Peroxisome Proliferators, pubmed-meshheading:11673457-Peroxisomes, pubmed-meshheading:11673457-Pyrimidines, pubmed-meshheading:11673457-Recombinant Fusion Proteins, pubmed-meshheading:11673457-Sequence Alignment, pubmed-meshheading:11673457-Substrate Specificity, pubmed-meshheading:11673457-Thiolester Hydrolases, pubmed-meshheading:11673457-Tissue Extracts
pubmed:year
2002
pubmed:articleTitle
Characterization of an acyl-coA thioesterase that functions as a major regulator of peroxisomal lipid metabolism.
pubmed:affiliation
Department of Medical Laboratory Sciences and Technology, Division of Clinical Chemistry, Karolinska Institutet, Huddinge University Hospital, SE-141 86 Stockholm, Sweden. mary.hunt@chemlab.hs.sll.se
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't