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)/(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.
Kasumov
Takhar
T
Department of Nutrition, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Adams
Jillian E
JE
Bian
Fang
F
David
France
F
Thomas
Katherine R
KR
Jobbins
Kathryn A
KA
Minkler
Paul E
PE
Hoppel
Charles L
CL
Brunengraber
Henri
H
D000085:Acetates / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000108:Acetylcarnitine / Q000378:metabolism; D000818:Animals; D002210:Caprylates / Q000378:metabolism*; D002247:Carbon Isotopes; D019343:Citric Acid / Q000378:metabolism; D007553:Isotope Labeling / Q000379:methods*; D007657:Ketone Bodies / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D010477:Perfusion; D020675:Peroxisomes / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000085:Acetates; D002210:Caprylates; D002247:Carbon Isotopes; D007657:Ketone Bodies; D019343:Citric Acid; D008316:Malonyl Coenzyme A; D000108:Acetylcarnitine; D000105:Acetyl Coenzyme A; C031492:octanoic acid