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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
1987-1-30
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pubmed:abstractText |
The effects of 2-tetradecylglycidic acid (TDGA), TDGA-CoA and TDGA-carnitine were examined in purified hepatic CPT (carnitine palmitoyltransferase) and in hepatic mitochondria and inverted submitochondrial vesicles derived from Sprague-Dawley rats. Since TDGA has been reported as a specific inhibitor of carnitine palmitoyltransferase-A (CPT-A), the focus was on kinetics and inhibition of CPT-A, and the relationship of this key enzyme to beta-oxidation. After administration of TDGA in vivo to overnight-starved rats, the Vmax. of CPT in intact mitochondria and in inverted vesicles (CPT-B) was depressed by 66%. The S0.5 for palmitoyl-CoA and Km for carnitine were unchanged. The I50 (concn. giving 50% inhibition) for malonyl-CoA was significantly increased from 20 to 141 microM in intact mitochondria, but unchanged (199 versus 268 microM) in inverted vesicles. The addition in vitro of TDGA-CoA (0-1.0 microM) gave I50 values of 0.29 and 0.27 microM (S.E.M. = 0.19) in intact mitochondria from fed and 48 h-starved rats, and 0.81 and 1.57 microM (S.E.M. = 0.29) for inverted vesicles derived from fed and starved rats. Addition in vitro of TDGA-carnitine to mitochondria from starved rats yielded an I50 value of 27.7 mM (S.E.M. = 12.2) for L-[methyl-14C]carnitine release from palmitoyl-L-[methyl-14C]carnitine and 0.64 mM (S.E.M. = 0.07) for palmitoyl-L-[methyl-14C]carnitine formation from L-[methyl-14C]carnitine in intact mitochondria. Inverted vesicles were not measurably sensitive to TDGA-carnitine up to 500 microM for the assay of L-[methyl-14C]carnitine release, but were as sensitive as intact mitochondria when inhibition was determined in the direction of palmitoyl-L-[methyl-14C]carnitine formation (I50 = 0.54 +/- 0.07 microM). When TDGA-CoA was added to intact mitochondria, then incubated for 5 min at room temperature and subsequently washed out, Vmax. of CPT decreased from 5.8 to 3.5 (S.E.M. = 0.6) in intact mitochondria, and from 17.2 to 6.3 (S.E.M. = 4.8) in inverted vesicles. The Km for L-carnitine and the S0.5 for palmitoyl-CoA increased 2-fold with TDGA-CoA pretreatment in both intact mitochondria and inverted vesicles. Detergent solubilization (0.05% Triton X-100) resulted in a complete loss of TDGA-CoA sensitivity (up to 1.0 microM measured). Sonicated mitochondria exhibited an I50 of 0.72 +/- 0.03 microM.(ABSTRACT TRUNCATED AT 400 WORDS)
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-1171098,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-222997,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-2408671,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-3743881,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-3840167,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-3933557,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-3954744,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-3969383,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-4091801,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-4319084,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-4417814,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-4630394,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-5058225,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-5432063,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-5461620,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-5749773,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-5970554,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-6016603,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-6030383,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-6157353,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-6490647,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-6547720,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-6614163,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-6630173,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-6704164,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-6743235,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-7128831,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-7275984,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-7311851,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-7366330,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3800962-7425647
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-tetradecylglycidic acid,
http://linkedlifedata.com/resource/pubmed/chemical/2-tetradecylglycidyl-coenzyme A,
http://linkedlifedata.com/resource/pubmed/chemical/Acyl Coenzyme A,
http://linkedlifedata.com/resource/pubmed/chemical/Acyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Azetidines,
http://linkedlifedata.com/resource/pubmed/chemical/Carnitine,
http://linkedlifedata.com/resource/pubmed/chemical/Carnitine O-Palmitoyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/Epoxy Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Ethers, Cyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoglycemic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Malonyl Coenzyme A,
http://linkedlifedata.com/resource/pubmed/chemical/Palmitoyl Coenzyme A
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0264-6021
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
238
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
801-9
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:3800962-Acyl Coenzyme A,
pubmed-meshheading:3800962-Acyltransferases,
pubmed-meshheading:3800962-Administration, Oral,
pubmed-meshheading:3800962-Animals,
pubmed-meshheading:3800962-Azetidines,
pubmed-meshheading:3800962-Carnitine,
pubmed-meshheading:3800962-Carnitine O-Palmitoyltransferase,
pubmed-meshheading:3800962-Epoxy Compounds,
pubmed-meshheading:3800962-Ethers, Cyclic,
pubmed-meshheading:3800962-Fatty Acids,
pubmed-meshheading:3800962-Female,
pubmed-meshheading:3800962-Fluorescence Polarization,
pubmed-meshheading:3800962-Hypoglycemic Agents,
pubmed-meshheading:3800962-Kinetics,
pubmed-meshheading:3800962-Liver,
pubmed-meshheading:3800962-Male,
pubmed-meshheading:3800962-Malonyl Coenzyme A,
pubmed-meshheading:3800962-Mitochondria, Liver,
pubmed-meshheading:3800962-Palmitoyl Coenzyme A,
pubmed-meshheading:3800962-Rats,
pubmed-meshheading:3800962-Rats, Inbred Strains
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pubmed:year |
1986
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pubmed:articleTitle |
Action in vivo and in vitro of 2-tetradecylglycidic acid, 2-tetradecylglycidyl-CoA and 2-tetradecylglycidylcarnitine on hepatic carnitine palmitoyltransferase.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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