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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 (758.2)
Author(s) -
Kerner Janos,
Minkler Paul,
Lesnefsky Edward,
Hoppel Charles
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.758.2
Subject(s) - palmitic acid , malonyl coa , palmitoylcarnitine , elongation , chemistry , carnitine , mitochondrion , coenzyme a , acyl coa , biochemistry , carnitine palmitoyltransferase i , beta oxidation , fatty acid , enzyme , materials science , reductase , metallurgy , ultimate tensile strength
Rat hearts were perfused with [1,2,3,4‐ 13 C 4 ]palmitic acid (M+4) and the isotopic patterns of myocardial acylcarnitines and acyl‐CoAs analyzed using UHPLC‐MS/MS. The 13 C‐enrichment in palmitoyl‐CoA and palmitoylcarnitine shows that little endogenous palmitate contributed to their formation. The stable isotope enrichment of acyl‐CoAs and acylcarnitines clearly shows that the perfused palmitate was β‐oxidized and chain elongated at the same time. The observed 13 C enrichment in acetyl‐CoA and acetylcarnitine and M+6 stearoyl‐CoA and stearoylcarnitine suggests that the majority of two‐carbon units for chain elongation are derived from β‐oxidation of [1,2,3,4‐ 13 C 4 ]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 and is supported by the identical 13 C‐enrichment in mitochondrial acetyl‐CoA and malonyl‐CoA. 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 chain elongate fatty acids using mitochondria‐derived two‐carbon units in a process localized to the outer surface of the mitochondrial outer membrane. Support: NIH, PO1 AG15885. Grant Funding Source : Supported by NIH