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Brain pyruvate and 2-oxoglutarate dehydrogenase complexes are mitochondrial targets of the CoA ester of the Refsum disease marker phytanic acid
Pyruvate and 2-oxoglutarate dehydrogenase complexes are strongly inhibited by phytanoyl-CoA (IC 50 ≈ 10 −6–10 −7 M). Palmitoyl-CoA is 10-fold less potent. Phytanic or palmitic acids have no inhibitory effect up to 0.3 mM. At the substrate saturation, the acyl-CoA’s affect the first and second enzyma...
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| Published in: | FEBS letters 2006-06, Vol.580 (14), p.3551-3557 |
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| Main Authors: | , , , |
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| cites | cdi_FETCH-LOGICAL-c4595-df49ded7bbfe7a59191a5c491ececf73615a9e00301589a358eba7c68aee27a83 |
| container_end_page | 3557 |
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| container_start_page | 3551 |
| container_title | FEBS letters |
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| creator | Bunik, Victoria I. Raddatz, Günter Wanders, Ronald J.A. Reiser, Georg |
| description | Pyruvate and 2-oxoglutarate dehydrogenase complexes are strongly inhibited by phytanoyl-CoA (IC
50
≈
10
−6–10
−7
M). Palmitoyl-CoA is 10-fold less potent. Phytanic or palmitic acids have no inhibitory effect up to 0.3
mM. At the substrate saturation, the acyl-CoA’s affect the first and second enzymatic components of the 2-oxoglutarate dehydrogenase complex, while the third component is inhibited only at a low saturation with its substrate dihydrolipoamide. Thus, key regulatory branch points of mitochondrial metabolism are targets of a cellular derivative of phytanic acid. Decreased activity of the complexes might therefore contribute to neurological symptoms upon accumulation of phytanic acid in Refsum disease. |
| doi_str_mv | 10.1016/j.febslet.2006.05.040 |
| format | article |
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50
≈
10
−6–10
−7
M). Palmitoyl-CoA is 10-fold less potent. Phytanic or palmitic acids have no inhibitory effect up to 0.3
mM. At the substrate saturation, the acyl-CoA’s affect the first and second enzymatic components of the 2-oxoglutarate dehydrogenase complex, while the third component is inhibited only at a low saturation with its substrate dihydrolipoamide. Thus, key regulatory branch points of mitochondrial metabolism are targets of a cellular derivative of phytanic acid. Decreased activity of the complexes might therefore contribute to neurological symptoms upon accumulation of phytanic acid in Refsum disease.</description><identifier>ISSN: 0014-5793</identifier><identifier>EISSN: 1873-3468</identifier><identifier>DOI: 10.1016/j.febslet.2006.05.040</identifier><identifier>PMID: 16737698</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>2-Oxo acid dehydrogenase complex ; 2-oxoglutarate dehydrogenase ; 2-oxoglutarate dehydrogenase complex ; Animals ; Biomarkers - metabolism ; Brain - enzymology ; Brain - metabolism ; Coenzyme A - chemistry ; Coenzyme A - metabolism ; dihydrolipoamide acetyltransferase ; dihydrolipoamide dehydrogenase ; dihydrolipoamide succinyltransferase ; E1o ; E1p ; E2o ; E2p ; Female ; Ketoglutarate Dehydrogenase Complex - metabolism ; Long chain acyl-CoA ; Models, Molecular ; Neurodegeneration ; OGDHC ; PDHC ; Peroxisomal inherited disorder ; Phytanic acid ; Phytanic Acid - analogs & derivatives ; Phytanic Acid - chemistry ; Phytanic Acid - metabolism ; pyruvate dehydrogenase ; pyruvate dehydrogenase complex ; Pyruvic Acid - metabolism ; Rats ; reactive oxygen species ; Refsum Disease - enzymology ; Refsum Disease - metabolism ; ROS ; ThDP ; Thiamine ; thiamine diphosphate</subject><ispartof>FEBS letters, 2006-06, Vol.580 (14), p.3551-3557</ispartof><rights>2006 Federation of European Biochemical Societies</rights><rights>FEBS Letters 580 (2006) 1873-3468 © 2015 Federation of European Biochemical Societies</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4595-df49ded7bbfe7a59191a5c491ececf73615a9e00301589a358eba7c68aee27a83</citedby><cites>FETCH-LOGICAL-c4595-df49ded7bbfe7a59191a5c491ececf73615a9e00301589a358eba7c68aee27a83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014579306006405$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3549,27924,27925,45780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16737698$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bunik, Victoria I.</creatorcontrib><creatorcontrib>Raddatz, Günter</creatorcontrib><creatorcontrib>Wanders, Ronald J.A.</creatorcontrib><creatorcontrib>Reiser, Georg</creatorcontrib><title>Brain pyruvate and 2-oxoglutarate dehydrogenase complexes are mitochondrial targets of the CoA ester of the Refsum disease marker phytanic acid</title><title>FEBS letters</title><addtitle>FEBS Lett</addtitle><description>Pyruvate and 2-oxoglutarate dehydrogenase complexes are strongly inhibited by phytanoyl-CoA (IC
50
≈
10
−6–10
−7
M). Palmitoyl-CoA is 10-fold less potent. Phytanic or palmitic acids have no inhibitory effect up to 0.3
mM. At the substrate saturation, the acyl-CoA’s affect the first and second enzymatic components of the 2-oxoglutarate dehydrogenase complex, while the third component is inhibited only at a low saturation with its substrate dihydrolipoamide. Thus, key regulatory branch points of mitochondrial metabolism are targets of a cellular derivative of phytanic acid. Decreased activity of the complexes might therefore contribute to neurological symptoms upon accumulation of phytanic acid in Refsum disease.</description><subject>2-Oxo acid dehydrogenase complex</subject><subject>2-oxoglutarate dehydrogenase</subject><subject>2-oxoglutarate dehydrogenase complex</subject><subject>Animals</subject><subject>Biomarkers - metabolism</subject><subject>Brain - enzymology</subject><subject>Brain - metabolism</subject><subject>Coenzyme A - chemistry</subject><subject>Coenzyme A - metabolism</subject><subject>dihydrolipoamide acetyltransferase</subject><subject>dihydrolipoamide dehydrogenase</subject><subject>dihydrolipoamide succinyltransferase</subject><subject>E1o</subject><subject>E1p</subject><subject>E2o</subject><subject>E2p</subject><subject>Female</subject><subject>Ketoglutarate Dehydrogenase Complex - metabolism</subject><subject>Long chain acyl-CoA</subject><subject>Models, Molecular</subject><subject>Neurodegeneration</subject><subject>OGDHC</subject><subject>PDHC</subject><subject>Peroxisomal inherited disorder</subject><subject>Phytanic acid</subject><subject>Phytanic Acid - analogs & derivatives</subject><subject>Phytanic Acid - chemistry</subject><subject>Phytanic Acid - metabolism</subject><subject>pyruvate dehydrogenase</subject><subject>pyruvate dehydrogenase complex</subject><subject>Pyruvic Acid - metabolism</subject><subject>Rats</subject><subject>reactive oxygen species</subject><subject>Refsum Disease - enzymology</subject><subject>Refsum Disease - metabolism</subject><subject>ROS</subject><subject>ThDP</subject><subject>Thiamine</subject><subject>thiamine diphosphate</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNqNkc1u1DAUhSMEotPCI4C8Ypdgx3Fsr1A7ammlSkj8rC3HvpnxkMTBTtrmKXhlHM0glmVl-d5zzr32l2XvCC4IJvXHQ9FCEzuYihLjusCswBV-kW2I4DSnVS1eZhuMSZUzLulZdh7jAae7IPJ1dkZqTnktxSb7fRW0G9C4hPlBT4D0YFGZ-ye_6-ZJh7VkYb_Y4Hcw6AjI-H7s4Aki0gFQ7yZv9n6wwekOJcMOpoh8i6Y9oK2_RBAnCH8LX6GNc4-si7BG9Tr8TM1xv0x6cAZp4-yb7FWruwhvT-dF9uPm-vv2Nr__8vlue3mfm4pJltu2khYsb5oWuGaSSKKZqSQBA6bltCZMS8CYYsKE1JQJaDQ3tdAAJdeCXmQfjrlj8L_mtKXqXTTQdXoAP0dVC0wZ5eWzwhJXUpCKJiE7Ck3wMQZo1RhceuKiCFYrMnVQJ2RqRaYwUwlZ8r0_DZibHuw_14lREtweBY-ug-X_UtXN9VX5beW_4sd16lSYpahPxyhIX_vgIKhoHAwGrAtgJmW9e2bbP1MIwvM</recordid><startdate>20060612</startdate><enddate>20060612</enddate><creator>Bunik, Victoria I.</creator><creator>Raddatz, Günter</creator><creator>Wanders, Ronald J.A.</creator><creator>Reiser, Georg</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</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>7TK</scope><scope>7X8</scope></search><sort><creationdate>20060612</creationdate><title>Brain pyruvate and 2-oxoglutarate dehydrogenase complexes are mitochondrial targets of the CoA ester of the Refsum disease marker phytanic acid</title><author>Bunik, Victoria I. ; Raddatz, Günter ; Wanders, Ronald J.A. ; Reiser, Georg</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4595-df49ded7bbfe7a59191a5c491ececf73615a9e00301589a358eba7c68aee27a83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>2-Oxo acid dehydrogenase complex</topic><topic>2-oxoglutarate dehydrogenase</topic><topic>2-oxoglutarate dehydrogenase complex</topic><topic>Animals</topic><topic>Biomarkers - metabolism</topic><topic>Brain - enzymology</topic><topic>Brain - metabolism</topic><topic>Coenzyme A - chemistry</topic><topic>Coenzyme A - metabolism</topic><topic>dihydrolipoamide acetyltransferase</topic><topic>dihydrolipoamide dehydrogenase</topic><topic>dihydrolipoamide succinyltransferase</topic><topic>E1o</topic><topic>E1p</topic><topic>E2o</topic><topic>E2p</topic><topic>Female</topic><topic>Ketoglutarate Dehydrogenase Complex - metabolism</topic><topic>Long chain acyl-CoA</topic><topic>Models, Molecular</topic><topic>Neurodegeneration</topic><topic>OGDHC</topic><topic>PDHC</topic><topic>Peroxisomal inherited disorder</topic><topic>Phytanic acid</topic><topic>Phytanic Acid - analogs & derivatives</topic><topic>Phytanic Acid - chemistry</topic><topic>Phytanic Acid - metabolism</topic><topic>pyruvate dehydrogenase</topic><topic>pyruvate dehydrogenase complex</topic><topic>Pyruvic Acid - metabolism</topic><topic>Rats</topic><topic>reactive oxygen species</topic><topic>Refsum Disease - enzymology</topic><topic>Refsum Disease - metabolism</topic><topic>ROS</topic><topic>ThDP</topic><topic>Thiamine</topic><topic>thiamine diphosphate</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bunik, Victoria I.</creatorcontrib><creatorcontrib>Raddatz, Günter</creatorcontrib><creatorcontrib>Wanders, Ronald J.A.</creatorcontrib><creatorcontrib>Reiser, Georg</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>FEBS letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bunik, Victoria I.</au><au>Raddatz, Günter</au><au>Wanders, Ronald J.A.</au><au>Reiser, Georg</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Brain pyruvate and 2-oxoglutarate dehydrogenase complexes are mitochondrial targets of the CoA ester of the Refsum disease marker phytanic acid</atitle><jtitle>FEBS letters</jtitle><addtitle>FEBS Lett</addtitle><date>2006-06-12</date><risdate>2006</risdate><volume>580</volume><issue>14</issue><spage>3551</spage><epage>3557</epage><pages>3551-3557</pages><issn>0014-5793</issn><eissn>1873-3468</eissn><abstract>Pyruvate and 2-oxoglutarate dehydrogenase complexes are strongly inhibited by phytanoyl-CoA (IC
50
≈
10
−6–10
−7
M). Palmitoyl-CoA is 10-fold less potent. Phytanic or palmitic acids have no inhibitory effect up to 0.3
mM. At the substrate saturation, the acyl-CoA’s affect the first and second enzymatic components of the 2-oxoglutarate dehydrogenase complex, while the third component is inhibited only at a low saturation with its substrate dihydrolipoamide. Thus, key regulatory branch points of mitochondrial metabolism are targets of a cellular derivative of phytanic acid. Decreased activity of the complexes might therefore contribute to neurological symptoms upon accumulation of phytanic acid in Refsum disease.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>16737698</pmid><doi>10.1016/j.febslet.2006.05.040</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 0014-5793 1873-3468 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68035372 |
| source | Wiley; ScienceDirect Journals |
| subjects | 2-Oxo acid dehydrogenase complex 2-oxoglutarate dehydrogenase 2-oxoglutarate dehydrogenase complex Animals Biomarkers - metabolism Brain - enzymology Brain - metabolism Coenzyme A - chemistry Coenzyme A - metabolism dihydrolipoamide acetyltransferase dihydrolipoamide dehydrogenase dihydrolipoamide succinyltransferase E1o E1p E2o E2p Female Ketoglutarate Dehydrogenase Complex - metabolism Long chain acyl-CoA Models, Molecular Neurodegeneration OGDHC PDHC Peroxisomal inherited disorder Phytanic acid Phytanic Acid - analogs & derivatives Phytanic Acid - chemistry Phytanic Acid - metabolism pyruvate dehydrogenase pyruvate dehydrogenase complex Pyruvic Acid - metabolism Rats reactive oxygen species Refsum Disease - enzymology Refsum Disease - metabolism ROS ThDP Thiamine thiamine diphosphate |
| title | Brain pyruvate and 2-oxoglutarate dehydrogenase complexes are mitochondrial targets of the CoA ester of the Refsum disease marker phytanic acid |
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