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  • Title: Probing peroxisomal beta-oxidation and the labelling of acetyl-CoA proxies with [1-(13C)]octanoate and [3-(13C)]octanoate in the perfused rat liver.
    Author: Kasumov T, Adams JE, Bian F, David F, Thomas KR, Jobbins KA, Minkler PE, Hoppel CL, Brunengraber H.
    Journal: Biochem J; 2005 Jul 15; 389(Pt 2):397-401. PubMed ID: 15773815.
    Abstract:
    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.
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