Stereochemistry of the α-oxidation of 3-methyl-branched fatty acids in rat liver
The stereochemistry of the α-oxidation of 3-methyl-branched fatty acids was studied in rat liver. R- and S-3-methylhexadecanoic acid were equally well α-oxidized in intact hepatocytes and homogenates. Subcellular fractionation studies showed that α-oxidation of both isomers is confined to peroxisome...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
1999-04-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520321398 |
| _version_ | 1818934967020814336 |
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| author | Kathleen Croes Minne Casteels Martine Dieuaide-Noubhani Guy P. Mannaerts Paul P. Van Veldhoven |
| author_facet | Kathleen Croes Minne Casteels Martine Dieuaide-Noubhani Guy P. Mannaerts Paul P. Van Veldhoven |
| author_sort | Kathleen Croes |
| collection | DOAJ |
| description | The stereochemistry of the α-oxidation of 3-methyl-branched fatty acids was studied in rat liver. R- and S-3-methylhexadecanoic acid were equally well α-oxidized in intact hepatocytes and homogenates. Subcellular fractionation studies showed that α-oxidation of both isomers is confined to peroxisomes. Dehydrogenation of 2-methylpentadecanal, the end-product of the peroxisomal α-oxidation of 3-methylhexadecanoic acid, to 2-methylpentadecanoic acid, followed by derivatization with R-1-phenylethylamine and subsequent separation of the stereoisomers by gas chromatography, revealed that the configuration of the methylbranch is preserved throughout the whole α-oxidation process. Metabolism and formation of the 2-hydroxy-3-methylhexadecanoyl-CoA intermediate were also investigated. Separation of the methyl esters of the four isomers of 2-hydroxy-3-methylhexadecanoic acid was achieved by gas chromatography after derivatization of the hydroxy group with R-2-methoxy-2-trifluoromethylphenylacetic acid chloride and the absolute configuration of the four isomers was determined. Although purified peroxisomes are capable of metabolizing all four isomers of 2-hydroxy-3-methylhexadecanoyl-CoA, they can only form the (2S,3R) and the (2R,3S) isomers. Our experiments exclude the racemization of the 3-methyl branch during the α-oxidation process. The configuration of the 3-methyl branch does not influence the rate of α-oxidation, but determines the side of the 2-hydroxylation, hence the configuration of the 2-hydroxy-3-methylacyl-CoA intermediates formed during the process.—Croes, K., M. Casteels, M. Dieuaide-Noubhani, G. P. Mannaerts, and P. P. Van Veldhoven. Stereochemistry of the α-oxidation of 3-methyl-branched fatty acids in rat liver. J. Lipid Res. 1999. 40: 601–609. |
| first_indexed | 2024-12-20T05:12:41Z |
| format | Article |
| id | doaj.art-699d88aee25544a2b568bada5e043649 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-20T05:12:41Z |
| publishDate | 1999-04-01 |
| publisher | Elsevier |
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| series | Journal of Lipid Research |
| spelling | doaj.art-699d88aee25544a2b568bada5e0436492022-12-21T19:52:14ZengElsevierJournal of Lipid Research0022-22751999-04-01404601609Stereochemistry of the α-oxidation of 3-methyl-branched fatty acids in rat liverKathleen Croes0Minne Casteels1Martine Dieuaide-Noubhani2Guy P. Mannaerts3Paul P. Van Veldhoven4To whom correspondence should be addressed.; Katholieke Universiteit Leuven, Campus Gasthuisberg, Departement Moleculaire Celbiologie, Afdeling Farmacologie, Herestraat 49, B-3000 Leuven, BelgiumKatholieke Universiteit Leuven, Campus Gasthuisberg, Departement Moleculaire Celbiologie, Afdeling Farmacologie, Herestraat 49, B-3000 Leuven, BelgiumKatholieke Universiteit Leuven, Campus Gasthuisberg, Departement Moleculaire Celbiologie, Afdeling Farmacologie, Herestraat 49, B-3000 Leuven, BelgiumKatholieke Universiteit Leuven, Campus Gasthuisberg, Departement Moleculaire Celbiologie, Afdeling Farmacologie, Herestraat 49, B-3000 Leuven, BelgiumKatholieke Universiteit Leuven, Campus Gasthuisberg, Departement Moleculaire Celbiologie, Afdeling Farmacologie, Herestraat 49, B-3000 Leuven, BelgiumThe stereochemistry of the α-oxidation of 3-methyl-branched fatty acids was studied in rat liver. R- and S-3-methylhexadecanoic acid were equally well α-oxidized in intact hepatocytes and homogenates. Subcellular fractionation studies showed that α-oxidation of both isomers is confined to peroxisomes. Dehydrogenation of 2-methylpentadecanal, the end-product of the peroxisomal α-oxidation of 3-methylhexadecanoic acid, to 2-methylpentadecanoic acid, followed by derivatization with R-1-phenylethylamine and subsequent separation of the stereoisomers by gas chromatography, revealed that the configuration of the methylbranch is preserved throughout the whole α-oxidation process. Metabolism and formation of the 2-hydroxy-3-methylhexadecanoyl-CoA intermediate were also investigated. Separation of the methyl esters of the four isomers of 2-hydroxy-3-methylhexadecanoic acid was achieved by gas chromatography after derivatization of the hydroxy group with R-2-methoxy-2-trifluoromethylphenylacetic acid chloride and the absolute configuration of the four isomers was determined. Although purified peroxisomes are capable of metabolizing all four isomers of 2-hydroxy-3-methylhexadecanoyl-CoA, they can only form the (2S,3R) and the (2R,3S) isomers. Our experiments exclude the racemization of the 3-methyl branch during the α-oxidation process. The configuration of the 3-methyl branch does not influence the rate of α-oxidation, but determines the side of the 2-hydroxylation, hence the configuration of the 2-hydroxy-3-methylacyl-CoA intermediates formed during the process.—Croes, K., M. Casteels, M. Dieuaide-Noubhani, G. P. Mannaerts, and P. P. Van Veldhoven. Stereochemistry of the α-oxidation of 3-methyl-branched fatty acids in rat liver. J. Lipid Res. 1999. 40: 601–609.http://www.sciencedirect.com/science/article/pii/S0022227520321398peroxisomephytanic acidRefsum's diseasehydroxylation |
| spellingShingle | Kathleen Croes Minne Casteels Martine Dieuaide-Noubhani Guy P. Mannaerts Paul P. Van Veldhoven Stereochemistry of the α-oxidation of 3-methyl-branched fatty acids in rat liver Journal of Lipid Research peroxisome phytanic acid Refsum's disease hydroxylation |
| title | Stereochemistry of the α-oxidation of 3-methyl-branched fatty acids in rat liver |
| title_full | Stereochemistry of the α-oxidation of 3-methyl-branched fatty acids in rat liver |
| title_fullStr | Stereochemistry of the α-oxidation of 3-methyl-branched fatty acids in rat liver |
| title_full_unstemmed | Stereochemistry of the α-oxidation of 3-methyl-branched fatty acids in rat liver |
| title_short | Stereochemistry of the α-oxidation of 3-methyl-branched fatty acids in rat liver |
| title_sort | stereochemistry of the α oxidation of 3 methyl branched fatty acids in rat liver |
| topic | peroxisome phytanic acid Refsum's disease hydroxylation |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520321398 |
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