Mechanism of the Inhibition of Cholesterol Absorption by DL-Melinamide: Inhibition of Cholesterol Esterification
In order to elucidate the mechanism of action of DL-melinamide [DL-MA, N-(α-methylbenzyl)linoleamide], an inhibitor of cholesterol absorption, the effect of DL-MA on esterification of cholesterol in the mucosa of rabbit small intestine was studied. DL-MA inhibited acyl CoA:cholesterol acyltransferas...
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| Veröffentlicht in: | Japanese journal of pharmacology 1986, Vol.42(4), pp.517-523 |
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| container_title | Japanese journal of pharmacology |
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| creator | NATORI, Kazuichi OKAZAKI, Yuko NAKAJIMA, Takeshi HIROHASHI, Toshiyuki AONO, Shunji |
| description | In order to elucidate the mechanism of action of DL-melinamide [DL-MA, N-(α-methylbenzyl)linoleamide], an inhibitor of cholesterol absorption, the effect of DL-MA on esterification of cholesterol in the mucosa of rabbit small intestine was studied. DL-MA inhibited acyl CoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) activity in the mucosal microsomes, with 50% inhibition occurring at approximately 0.5 μM. On the other hand, DL-MA had no effect on the cholesterol esterase (EC 3.1.1.13) activity in the mucosal cytosol. Kinetic studies indicate that DL-MA is an uncompetitive inhibitor of ACAT. D-MA, one of the two optical isomers of DL-MA, was found to be a more effective inhibitor of ACAT than L-MA, another isomer. This finding indicates that the inhibition of cholesterol absorption by DL-MA depends on the inhibition of ACAT by this compound, in view of the fact that D-MA is a more effective inhibitor of cholesterol absorption than L-MA. |
| doi_str_mv | 10.1254/jjp.42.517 |
| format | Article |
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DL-MA inhibited acyl CoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) activity in the mucosal microsomes, with 50% inhibition occurring at approximately 0.5 μM. On the other hand, DL-MA had no effect on the cholesterol esterase (EC 3.1.1.13) activity in the mucosal cytosol. Kinetic studies indicate that DL-MA is an uncompetitive inhibitor of ACAT. D-MA, one of the two optical isomers of DL-MA, was found to be a more effective inhibitor of ACAT than L-MA, another isomer. This finding indicates that the inhibition of cholesterol absorption by DL-MA depends on the inhibition of ACAT by this compound, in view of the fact that D-MA is a more effective inhibitor of cholesterol absorption than L-MA.</description><identifier>ISSN: 0021-5198</identifier><identifier>EISSN: 1347-3506</identifier><identifier>DOI: 10.1254/jjp.42.517</identifier><identifier>PMID: 3807053</identifier><identifier>CODEN: JJPAAZ</identifier><language>eng</language><publisher>Kyoto: The Japanese Pharmacological Society</publisher><subject>Acrylamides - pharmacology ; Animals ; Biological and medical sciences ; Cholesterol - metabolism ; Esterification ; General and cellular metabolism. Vitamins ; In Vitro Techniques ; Intestinal Absorption - drug effects ; Intestinal Mucosa - metabolism ; Linoleic Acids - pharmacology ; Male ; Medical sciences ; Pharmacology. Drug treatments ; Polyunsaturated Alkamides ; Rabbits ; Stereoisomerism ; Sterol O-Acyltransferase - antagonists & inhibitors ; Triglycerides - biosynthesis</subject><ispartof>The Japanese Journal of Pharmacology, 1986, Vol.42(4), pp.517-523</ispartof><rights>1986 Elsevier B.V.</rights><rights>The Japanese PharmacologicalSociety</rights><rights>1987 INIST-CNRS</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c620t-bca3df8491a02f2d0683e6fe2c63b27e9f50b60ebbfe5be5ab202fd9d7644fd3</citedby><cites>FETCH-LOGICAL-c620t-bca3df8491a02f2d0683e6fe2c63b27e9f50b60ebbfe5be5ab202fd9d7644fd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1883,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=8341360$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3807053$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>NATORI, Kazuichi</creatorcontrib><creatorcontrib>OKAZAKI, Yuko</creatorcontrib><creatorcontrib>NAKAJIMA, Takeshi</creatorcontrib><creatorcontrib>HIROHASHI, Toshiyuki</creatorcontrib><creatorcontrib>AONO, Shunji</creatorcontrib><title>Mechanism of the Inhibition of Cholesterol Absorption by DL-Melinamide: Inhibition of Cholesterol Esterification</title><title>Japanese journal of pharmacology</title><addtitle>Jpn.J.Pharmacol.</addtitle><description>In order to elucidate the mechanism of action of DL-melinamide [DL-MA, N-(α-methylbenzyl)linoleamide], an inhibitor of cholesterol absorption, the effect of DL-MA on esterification of cholesterol in the mucosa of rabbit small intestine was studied. DL-MA inhibited acyl CoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) activity in the mucosal microsomes, with 50% inhibition occurring at approximately 0.5 μM. On the other hand, DL-MA had no effect on the cholesterol esterase (EC 3.1.1.13) activity in the mucosal cytosol. Kinetic studies indicate that DL-MA is an uncompetitive inhibitor of ACAT. D-MA, one of the two optical isomers of DL-MA, was found to be a more effective inhibitor of ACAT than L-MA, another isomer. This finding indicates that the inhibition of cholesterol absorption by DL-MA depends on the inhibition of ACAT by this compound, in view of the fact that D-MA is a more effective inhibitor of cholesterol absorption than L-MA.</description><subject>Acrylamides - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cholesterol - metabolism</subject><subject>Esterification</subject><subject>General and cellular metabolism. Vitamins</subject><subject>In Vitro Techniques</subject><subject>Intestinal Absorption - drug effects</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Linoleic Acids - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Polyunsaturated Alkamides</subject><subject>Rabbits</subject><subject>Stereoisomerism</subject><subject>Sterol O-Acyltransferase - antagonists & inhibitors</subject><subject>Triglycerides - biosynthesis</subject><issn>0021-5198</issn><issn>1347-3506</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1986</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtv1DAUhS0EKkNhwx4pC8QCKYOfebCrpgUqTcWme8uPa-IoiYOdqdR_j0NGs0JsfOV7Pp9rHyP0nuA9oYJ_6ft5z-lekPoF2hHG65IJXL1EO4wpKQVpm9foTUp93jaY8Ct0xRpcY8F2aH4A06nJp7EIrlg6KO6nzmu_-DCtnUMXBkgLxDAUNzqFOP9V9HNxeywfYPCTGr2Fr_85drdW77xRq_oWvXJqSPDuXK_R47e7x8OP8vjz-_3h5liaiuKl1EYx6xreEoWpoxZXDYPKATUV07SG1gmsKwxaOxAahNI0c7a1dcW5s-wafdps5xh-n_JV5OiTgWFQE4RTknVNRcu4yODnDTQxpBTByTn6UcVnSbBc05U5XcmpzOlm-MPZ9aRHsBf0HGfWP551lYwaXFST8emCNYwTVuGM3W5Ynxb1Cy66ios3A8h-7hJpBVnH8m3J0y9y_rAoYco2fLOBnOOThyiT8TAZsD6CWaQN_l-P-AOOD66U</recordid><startdate>1986</startdate><enddate>1986</enddate><creator>NATORI, Kazuichi</creator><creator>OKAZAKI, Yuko</creator><creator>NAKAJIMA, Takeshi</creator><creator>HIROHASHI, Toshiyuki</creator><creator>AONO, Shunji</creator><general>The Japanese Pharmacological Society</general><general>Japanese Pharmacological Society</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><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>1986</creationdate><title>Mechanism of the Inhibition of Cholesterol Absorption by DL-Melinamide: Inhibition of Cholesterol Esterification</title><author>NATORI, Kazuichi ; OKAZAKI, Yuko ; NAKAJIMA, Takeshi ; HIROHASHI, Toshiyuki ; AONO, Shunji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c620t-bca3df8491a02f2d0683e6fe2c63b27e9f50b60ebbfe5be5ab202fd9d7644fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1986</creationdate><topic>Acrylamides - pharmacology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cholesterol - metabolism</topic><topic>Esterification</topic><topic>General and cellular metabolism. Vitamins</topic><topic>In Vitro Techniques</topic><topic>Intestinal Absorption - drug effects</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Linoleic Acids - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Pharmacology. 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DL-MA inhibited acyl CoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) activity in the mucosal microsomes, with 50% inhibition occurring at approximately 0.5 μM. On the other hand, DL-MA had no effect on the cholesterol esterase (EC 3.1.1.13) activity in the mucosal cytosol. Kinetic studies indicate that DL-MA is an uncompetitive inhibitor of ACAT. D-MA, one of the two optical isomers of DL-MA, was found to be a more effective inhibitor of ACAT than L-MA, another isomer. This finding indicates that the inhibition of cholesterol absorption by DL-MA depends on the inhibition of ACAT by this compound, in view of the fact that D-MA is a more effective inhibitor of cholesterol absorption than L-MA.</abstract><cop>Kyoto</cop><pub>The Japanese Pharmacological Society</pub><pmid>3807053</pmid><doi>10.1254/jjp.42.517</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0021-5198 |
| ispartof | The Japanese Journal of Pharmacology, 1986, Vol.42(4), pp.517-523 |
| issn | 0021-5198 1347-3506 |
| language | eng |
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| source | J-STAGE Free; MEDLINE; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Acrylamides - pharmacology Animals Biological and medical sciences Cholesterol - metabolism Esterification General and cellular metabolism. Vitamins In Vitro Techniques Intestinal Absorption - drug effects Intestinal Mucosa - metabolism Linoleic Acids - pharmacology Male Medical sciences Pharmacology. Drug treatments Polyunsaturated Alkamides Rabbits Stereoisomerism Sterol O-Acyltransferase - antagonists & inhibitors Triglycerides - biosynthesis |
| title | Mechanism of the Inhibition of Cholesterol Absorption by DL-Melinamide: Inhibition of Cholesterol Esterification |
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