Acyl-CoA Synthetase Isoforms 1, 4, and 5 Are Present in Different Subcellular Membranes in Rat Liver and Can Be Inhibited Independently
Inhibition studies have suggested that acyl-CoA synthetase (ACS, EC 6.2.1.3 ) isoforms might regulate the use of acyl-CoAs by different metabolic pathways. In order to determine whether the subcellular locations differed for each of the three ACSs present in liver and whether these isoforms were reg...
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| Veröffentlicht in: | The Journal of biological chemistry 2001-07, Vol.276 (27), p.24674-24679 |
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| creator | Lewin, T M Kim, J H Granger, D A Vance, J E Coleman, R A |
| description | Inhibition studies have suggested that acyl-CoA synthetase (ACS, EC 6.2.1.3 ) isoforms might regulate the use of acyl-CoAs by different metabolic pathways. In order to determine whether the subcellular
locations differed for each of the three ACSs present in liver and whether these isoforms were regulated independently, non-cross-reacting
peptide antibodies were raised against ACS1, ACS4, and ACS5. ACS1 was identified in endoplasmic reticulum, mitochondria-associated
membrane (MAM), and cytosol, but not in mitochondria. ACS4 was present primarily in MAM, and the 76-kDa ACS5 protein was located
in mitochondrial membrane. Consistent with these locations, N -ethylmaleimide, an inhibitor of ACS4, inhibited ACS activity 47% in MAM and 28% in endoplasmic reticulum. Troglitazone, a
second ACS4 inhibitor, inhibited ACS activity |
| doi_str_mv | 10.1074/jbc.M102036200 |
| format | Article |
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locations differed for each of the three ACSs present in liver and whether these isoforms were regulated independently, non-cross-reacting
peptide antibodies were raised against ACS1, ACS4, and ACS5. ACS1 was identified in endoplasmic reticulum, mitochondria-associated
membrane (MAM), and cytosol, but not in mitochondria. ACS4 was present primarily in MAM, and the 76-kDa ACS5 protein was located
in mitochondrial membrane. Consistent with these locations, N -ethylmaleimide, an inhibitor of ACS4, inhibited ACS activity 47% in MAM and 28% in endoplasmic reticulum. Troglitazone, a
second ACS4 inhibitor, inhibited ACS activity <10% in microsomes and mitochondria and 45% in MAM. Triacsin C, a competitive
inhibitor of both ACS1 and ACS4, inhibited ACS activity similarly in endoplasmic reticulum, MAM, and mitochondria, suggesting
that a hitherto unidentified triacsin-sensitive ACS is present in mitochondria. ACS1, ACS4, and ACS5 were regulated independently
by fasting and re-feeding. Fasting rats for 48 h resulted in a decrease in ACS4 protein, and an increase in ACS5. Re-feeding
normal chow or a high sucrose diet for 24 h after a 48-h fast increased both ACS1 and ACS4 protein expression 1.5â2.0-fold,
consistent with inhibition studies. These results suggest that ACS1 and ACS4 may be linked to triacylglycerol synthesis. Taken
together, the data suggest that acyl-CoAs may be functionally channeled to specific metabolic pathways through different ACS
isoforms in unique subcellular locations.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M102036200</identifier><identifier>PMID: 11319232</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>Amino Acid Sequence ; Animals ; Antibody Specificity ; Chromans - pharmacology ; Coenzyme A Ligases - antagonists & inhibitors ; Dietary Sucrose - pharmacology ; Ethylmaleimide - pharmacology ; Fasting ; Intracellular Membranes - enzymology ; Liver - enzymology ; Mitochondrial Proteins ; Molecular Sequence Data ; Rats ; Subcellular Fractions - enzymology ; Thiazoles - pharmacology ; Thiazolidinediones ; Triazenes - pharmacology ; Triglycerides - biosynthesis ; Troglitazone</subject><ispartof>The Journal of biological chemistry, 2001-07, Vol.276 (27), p.24674-24679</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c405t-c41c2ef702403c60d5f1803e660f5d0b8f0051c0433f501bae3fb0c45f842df53</citedby><cites>FETCH-LOGICAL-c405t-c41c2ef702403c60d5f1803e660f5d0b8f0051c0433f501bae3fb0c45f842df53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11319232$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lewin, T M</creatorcontrib><creatorcontrib>Kim, J H</creatorcontrib><creatorcontrib>Granger, D A</creatorcontrib><creatorcontrib>Vance, J E</creatorcontrib><creatorcontrib>Coleman, R A</creatorcontrib><title>Acyl-CoA Synthetase Isoforms 1, 4, and 5 Are Present in Different Subcellular Membranes in Rat Liver and Can Be Inhibited Independently</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Inhibition studies have suggested that acyl-CoA synthetase (ACS, EC 6.2.1.3 ) isoforms might regulate the use of acyl-CoAs by different metabolic pathways. In order to determine whether the subcellular
locations differed for each of the three ACSs present in liver and whether these isoforms were regulated independently, non-cross-reacting
peptide antibodies were raised against ACS1, ACS4, and ACS5. ACS1 was identified in endoplasmic reticulum, mitochondria-associated
membrane (MAM), and cytosol, but not in mitochondria. ACS4 was present primarily in MAM, and the 76-kDa ACS5 protein was located
in mitochondrial membrane. Consistent with these locations, N -ethylmaleimide, an inhibitor of ACS4, inhibited ACS activity 47% in MAM and 28% in endoplasmic reticulum. Troglitazone, a
second ACS4 inhibitor, inhibited ACS activity <10% in microsomes and mitochondria and 45% in MAM. Triacsin C, a competitive
inhibitor of both ACS1 and ACS4, inhibited ACS activity similarly in endoplasmic reticulum, MAM, and mitochondria, suggesting
that a hitherto unidentified triacsin-sensitive ACS is present in mitochondria. ACS1, ACS4, and ACS5 were regulated independently
by fasting and re-feeding. Fasting rats for 48 h resulted in a decrease in ACS4 protein, and an increase in ACS5. Re-feeding
normal chow or a high sucrose diet for 24 h after a 48-h fast increased both ACS1 and ACS4 protein expression 1.5â2.0-fold,
consistent with inhibition studies. These results suggest that ACS1 and ACS4 may be linked to triacylglycerol synthesis. Taken
together, the data suggest that acyl-CoAs may be functionally channeled to specific metabolic pathways through different ACS
isoforms in unique subcellular locations.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibody Specificity</subject><subject>Chromans - pharmacology</subject><subject>Coenzyme A Ligases - antagonists & inhibitors</subject><subject>Dietary Sucrose - pharmacology</subject><subject>Ethylmaleimide - pharmacology</subject><subject>Fasting</subject><subject>Intracellular Membranes - enzymology</subject><subject>Liver - enzymology</subject><subject>Mitochondrial Proteins</subject><subject>Molecular Sequence Data</subject><subject>Rats</subject><subject>Subcellular Fractions - enzymology</subject><subject>Thiazoles - pharmacology</subject><subject>Thiazolidinediones</subject><subject>Triazenes - pharmacology</subject><subject>Triglycerides - biosynthesis</subject><subject>Troglitazone</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1vEzEQhi0EomngyhH5gDh1w_hrd3MMoUClVCAKEjfL9o5ZV_uR2rug_AL-Ng6JVEszHkuPH41eQl4xWDGo5Lt761a3DDiIkgM8IQsGtSiEYj-fkgUAZ8Waq_qCXKZ0D_nINXtOLhgTbM0FX5C_G3foiu24oXeHYWpxMgnpTRr9GPtE2RWVV9QMDVV0E5F-jZhwmGgY6IfgPcbj4262Drtu7kykt9jbaAZMR-Sbmegu_Mb437A1A32f3UMbbJiwyVODe8xtmLrDC_LMmy7hy_O9JD8-Xn_ffi52Xz7dbDe7wklQU-7McfQVcAnCldAoz2oQWJbgVQO29gCKOZBCeAXMGhTegpPK15I3XokleXvy7uP4MGOadB_Scf289DgnXcG6FJCVS7I6gS6OKUX0eh9Db-JBM9DH6HWOXj9Gnz-8Pptn22PziJ-zzsCbE9CGX-2fEFHbMLoWe82rMpfmsqyk-Aeyu4mu</recordid><startdate>20010706</startdate><enddate>20010706</enddate><creator>Lewin, T M</creator><creator>Kim, J H</creator><creator>Granger, D A</creator><creator>Vance, J E</creator><creator>Coleman, R A</creator><general>American Society for Biochemistry and Molecular Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20010706</creationdate><title>Acyl-CoA Synthetase Isoforms 1, 4, and 5 Are Present in Different Subcellular Membranes in Rat Liver and Can Be Inhibited Independently</title><author>Lewin, T M ; Kim, J H ; Granger, D A ; Vance, J E ; Coleman, R A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c405t-c41c2ef702403c60d5f1803e660f5d0b8f0051c0433f501bae3fb0c45f842df53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibody Specificity</topic><topic>Chromans - pharmacology</topic><topic>Coenzyme A Ligases - antagonists & inhibitors</topic><topic>Dietary Sucrose - pharmacology</topic><topic>Ethylmaleimide - pharmacology</topic><topic>Fasting</topic><topic>Intracellular Membranes - enzymology</topic><topic>Liver - enzymology</topic><topic>Mitochondrial Proteins</topic><topic>Molecular Sequence Data</topic><topic>Rats</topic><topic>Subcellular Fractions - enzymology</topic><topic>Thiazoles - pharmacology</topic><topic>Thiazolidinediones</topic><topic>Triazenes - pharmacology</topic><topic>Triglycerides - biosynthesis</topic><topic>Troglitazone</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lewin, T M</creatorcontrib><creatorcontrib>Kim, J H</creatorcontrib><creatorcontrib>Granger, D A</creatorcontrib><creatorcontrib>Vance, J E</creatorcontrib><creatorcontrib>Coleman, R A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lewin, T M</au><au>Kim, J H</au><au>Granger, D A</au><au>Vance, J E</au><au>Coleman, R A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acyl-CoA Synthetase Isoforms 1, 4, and 5 Are Present in Different Subcellular Membranes in Rat Liver and Can Be Inhibited Independently</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2001-07-06</date><risdate>2001</risdate><volume>276</volume><issue>27</issue><spage>24674</spage><epage>24679</epage><pages>24674-24679</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Inhibition studies have suggested that acyl-CoA synthetase (ACS, EC 6.2.1.3 ) isoforms might regulate the use of acyl-CoAs by different metabolic pathways. In order to determine whether the subcellular
locations differed for each of the three ACSs present in liver and whether these isoforms were regulated independently, non-cross-reacting
peptide antibodies were raised against ACS1, ACS4, and ACS5. ACS1 was identified in endoplasmic reticulum, mitochondria-associated
membrane (MAM), and cytosol, but not in mitochondria. ACS4 was present primarily in MAM, and the 76-kDa ACS5 protein was located
in mitochondrial membrane. Consistent with these locations, N -ethylmaleimide, an inhibitor of ACS4, inhibited ACS activity 47% in MAM and 28% in endoplasmic reticulum. Troglitazone, a
second ACS4 inhibitor, inhibited ACS activity <10% in microsomes and mitochondria and 45% in MAM. Triacsin C, a competitive
inhibitor of both ACS1 and ACS4, inhibited ACS activity similarly in endoplasmic reticulum, MAM, and mitochondria, suggesting
that a hitherto unidentified triacsin-sensitive ACS is present in mitochondria. ACS1, ACS4, and ACS5 were regulated independently
by fasting and re-feeding. Fasting rats for 48 h resulted in a decrease in ACS4 protein, and an increase in ACS5. Re-feeding
normal chow or a high sucrose diet for 24 h after a 48-h fast increased both ACS1 and ACS4 protein expression 1.5â2.0-fold,
consistent with inhibition studies. These results suggest that ACS1 and ACS4 may be linked to triacylglycerol synthesis. Taken
together, the data suggest that acyl-CoAs may be functionally channeled to specific metabolic pathways through different ACS
isoforms in unique subcellular locations.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>11319232</pmid><doi>10.1074/jbc.M102036200</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Amino Acid Sequence Animals Antibody Specificity Chromans - pharmacology Coenzyme A Ligases - antagonists & inhibitors Dietary Sucrose - pharmacology Ethylmaleimide - pharmacology Fasting Intracellular Membranes - enzymology Liver - enzymology Mitochondrial Proteins Molecular Sequence Data Rats Subcellular Fractions - enzymology Thiazoles - pharmacology Thiazolidinediones Triazenes - pharmacology Triglycerides - biosynthesis Troglitazone |
| title | Acyl-CoA Synthetase Isoforms 1, 4, and 5 Are Present in Different Subcellular Membranes in Rat Liver and Can Be Inhibited Independently |
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