Peroxisomal and mitochondrial oxidation of fatty acids in the heart, assessed from the 13C labeling of malonyl-CoA and the acetyl moiety of citrate.
We previously showed that a fraction of the acetyls used to synthesize malonyl-CoA in rat heart derives from partial peroxisomal oxidation of very long and long-chain fatty acids. The 13C labeling ratio (malonyl-CoA)/(acetyl moiety of citrate) was >1.0 with 13C-fatty acids, which yields [13C]acetyl-CoA in both mitochondria and peroxisomes and < 1.0 with substrates, which yields [13C]acetyl-CoA only in mitochondria. In this study, we tested the influence of 13C-fatty acid concentration and chain length on the labeling of acetyl-CoA formed in mitochondria and/or peroxisomes. Hearts were perfused with increasing concentrations of labeled docosanoate, oleate, octanoate, hexanoate, butyrate, acetate, or dodecanedioate. In contrast to the liver, peroxisomal oxidation of 1-13C-fatty acids in heart does not form [1-13C]acetate. With [1-13C]docosanoate and [1,12-13C2]dodecanedioate, malonyl-CoA enrichment plateaued at 11 and 9%, respectively, with no detectable labeling of the acetyl moiety of citrate. Thus, in the intact rat heart, docosanoate and dodecanedioate appear to be oxidized only in peroxisomes. With [1-13C]oleate or [1-13C]octanoate, the labeling ratio >1 indicates the partial peroxisomal oxidation of oleate and octanoate. In contrast, with [3-13C]octanoate, [1-13C]hexanoate, [1-13C]butyrate, or [1,2-13C2]acetate, the labeling ratio was <0.7 at all concentrations. Therefore, in rat heart, (i) n-fatty acids shorter than 8 carbons do not undergo peroxisomal oxidation, (ii) octanoate undergoes only one cycle of peroxisomal beta-oxidation, (iii) there is no detectable transfer to the mitochondria of acetyl-CoA from the cytosol or the peroxisomes, and (iv) the capacity of C2-C18 fatty acids to generate mitochondrial acetyl-CoA decreases with chain length.
Bian
Fang
F
Department of Nutrition, Case Western Reserve University, Cleveland Ohio 44106, USA.
Kasumov
Takhar
T
Thomas
Katherine R
KR
Jobbins
Kathryn A
KA
David
France
F
Minkler
Paul E
PE
Hoppel
Charles L
CL
Brunengraber
Henri
H
D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000107:Acetylation; D000108:Acetylcarnitine / Q000378:metabolism; D000818:Animals; D002247:Carbon Isotopes; D002951:Citrates / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002247:Carbon Isotopes; D002951:Citrates; D005230:Fatty Acids, Nonesterified; D008316:Malonyl Coenzyme A; D000108:Acetylcarnitine; D000105:Acetyl Coenzyme A