Synthesis of citrate from phosphoenolpyruvate and acetylcarnitine by mitochondria from rabbit, pigeon and rat liver: implications for lipogenesis.
Rabbit, pigeon and rat liver mitochondria convert exogenous phosphoenolpyruvate and acetylcarnitine to citrate at rates of 14, 74 and 8 nmol/15 min/mg protein. Citrate formation is dependent on exogenous HCO3-, is increased consistently by exogenous nucleotides (GDP, IDP, GTP, ADP, ATP) and inhibited strongly by 3-mercaptopicolinate and 1,2,3-benzenetricarboxylate. Citrate is not made from pyruvate alone or combined with acetylcarnitine. Pigeon and rat liver mitochondria make large amounts of citrate from exogenous succinate, suggesting the presence of an endogenous source of acetyl units or means of converting oxalacetate to acetyl units. Citrate synthesis from succinate by pigeon and rabbit mitochondria is increased significantly by exogenous acetylcarnitine. Pigeon and rat liver contain 80 and 15 times, respectively, more ATP:citrate lyase activity than does rabbit liver. Data suggest that mitochondrial phosphoenolpyruvate carboxykinase in vivo could convert glycolysis-derived phosphoenolpyruvate to oxalacetate that, with acetyl CoA, could form citrate for export to support cytosolic lipogenesis as an activator of acetyl CoA carboxylase, a carbon source via ATP:citrate lyase and NADPH via NADP:malate dehydrogenase or NADP:isocitrate dehydrogenase.
Wiese
T J
TJ
Department of Biochemistry and Molecular Biology, University of North Dakota School of Medicine, Grand Forks 58202, USA.
Wuensch
S A
SA
Ray
P D
PD
D000108:Acetylcarnitine / Q000378:metabolism*; D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D019343:Citric Acid / Q000378:metabolism*; D010856:Columbidae; D003600:Cytosol / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D007652:Oxo-Acid-Lyases / Q000378:metabolism; D010728:Phosphoenolpyruvate / Q000378:metabolism*; D010848:Picolinic Acids / Q000494:pharmacology; D019289:Pyruvic Acid / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid; D014233:Tricarboxylic Acids / Q000494:pharmacology
D001555:Benzene Derivatives; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D010848:Picolinic Acids; D013386:Succinates; D014233:Tricarboxylic Acids; C020723:citrate-binding transport protein; D019343:Citric Acid; C004288:benzene 1,2,3-tricarboxylic acid; D000108:Acetylcarnitine; D010728:Phosphoenolpyruvate; C008363:3-mercaptopicolinic acid; D019289:Pyruvic Acid; D019802:Succinic Acid; D007521:Isocitrate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D007652:Oxo-Acid-Lyases; C019909:citrate (pro-3S)-lyase