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Fatty acid chain elongation in palmitate-perfused working rat heart: mitochondrial acetyl-CoA is the source of two-carbon units for chain elongation.
MedLine Citation:
PMID:  24558043     Owner:  NLM     Status:  Publisher    
Rat hearts were perfused with [1,2,3,4-(13)C4]palmitic acid (M+4), and the isotopic patterns of myocardial acylcarnitines and acyl-CoAs analyzed using UHPLC-MS/MS. The 91.2% (13)C-enrichment in palmitoylcarnitine shows that little endogenous (M+0) palmitate contributed to its formation. The presence of M+2 myristoylcarnitine (95.7%) and M+2 acetylcarnitine (19.4%) is evidence for β-oxidation of perfused M+4 palmitic acid. Identical enrichment data were obtained in the respective acyl-CoAs. The relative (13)C-enrichment in M+4 (84.7%, 69.9%) and M+6 (16.2%, 17.8%) in stearoyl- and arachidylcarnitine, respectively, clearly shows that the perfused palmitate is chain elongated. The observed enrichment of (13)C in acetylcarnitine( 19%), M+6 stearoylcarnitine (16.2%), and M+6 arachidylcarnitine (17.8%) suggests that the majority of two-carbon units for chain elongation are derived from β-oxidation of [1,2,3,4-(13)C4]palmitic acid. These data are explained by conversion of the M+2 acetyl-CoA to M+2 malonyl-CoA, which serves as the acceptor for M+4 palmitoyl-CoA in chain elongation. Indeed, the (13)C-enrichment in mitochondrial acetyl-CoA (18.9%) and malonyl-CoA (19.9%) are identical. No (13)C-enrichment was found in acylcarnitine species with carbon chain lengths between four and twelve, arguing against the simple reversal of fatty acid β-oxidation. Furthermore, isolated, intact rat heart mitochondria 1) synthesize malonyl-CoA with simultaneous inhibition of carnitine palmitoyltransferase 1b, and 2) catalyze the palmitoyl-CoA-dependent incorporation of (14)C from [2-(14)C]malonyl-CoA into lipid-soluble products. In conclusion, rat heart has the capability to chain elongate fatty acids using mitochondria-derived two-carbon chain extenders. The data suggest that the chain elongation process is localized on the outer surface of the mitochondrial outer membrane.
Janos Kerner; Paul E Minkler; Edward J Lesnefsky; Charles L Hoppel
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-2-20
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  -     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2014 Feb 
Date Detail:
Created Date:  2014-2-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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