Probing peroxisomal beta-oxidation and the labelling of acetyl-CoA proxies with [1-(13C)]octanoate and [3-(13C)]octanoate in the perfused rat liver

We reported previously that a substantial fraction of the acetyl groups used to synthesize malonyl-CoA in rat heart is derived from peroxisomal beta-oxidation of long-chain and very-long-chain fatty acids. This conclusion was based on the interpretation of the 13C-labelling ratio (malonyl-CoA)/(acet...

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Published in:Biochemical journal 2005-07, Vol.389 (Pt 2), p.397-401
Main Authors: Kasumov, Takhar, Adams, Jillian E, Bian, Fang, David, France, Thomas, Katherine R, Jobbins, Kathryn A, Minkler, Paul E, Hoppel, Charles L, Brunengraber, Henri
Format: Article
Language:English
Subjects:
Acetates - metabolism
Acetyl Coenzyme A - metabolism
Acetylcarnitine - metabolism
Animals
Caprylates - metabolism
Carbon Isotopes
Citric Acid - metabolism
Isotope Labeling - methods
Ketone Bodies - metabolism
Liver - metabolism
Male
Malonyl Coenzyme A - metabolism
Mitochondria, Liver - metabolism
Oxidation-Reduction
Perfusion
Peroxisomes - metabolism
Rats
Rats, Sprague-Dawley
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Summary:We reported previously that a substantial fraction of the acetyl groups used to synthesize malonyl-CoA in rat heart is derived from peroxisomal beta-oxidation of long-chain and very-long-chain fatty acids. This conclusion was based on the interpretation of the 13C-labelling ratio (malonyl-CoA)/(acetyl moiety of citrate) measured in the presence of substrates that label acetyl-CoA in mitochondria only (ratio < 1.0) or in both mitochondria and peroxisomes (ratio > 1.0). The goals of the present study were to test, in rat livers perfused with [1-(13C)]octanoate or [3-(13C)]octanoate, (i) whether peroxisomal beta-oxidation contributes acetyl groups for malonyl-CoA synthesis, and (ii) the degree of labelling homogeneity of acetyl-CoA proxies (acetyl moiety of citrate, acetate, beta-hydroxybutyrate, malonyl-CoA and acetylcarnitine). Our data show that (i) octanoate undergoes two cycles of peroxisomal beta-oxidation in liver, (ii) acetyl groups formed in peroxisomes contribute to malonyl-CoA synthesis, (iii) the labelling of acetyl-CoA proxies is markedly heterogeneous, and (iv) the labelling of C1+2 of beta-hydroxybutyrate does not reflect the labelling of acetyl-CoA used in the citric acid cycle.
ISSN:0264-6021
1470-8728
DOI:10.1042/BJ20050144