Synthesis of phosphoenolpyruvate from propionate in sheep liver.
1. Utilization of propionate by sheep liver mitochondria was stimulated equally by pyruvate or alpha-oxoglutarate, with formation predominantly of malate. Pyruvate increased conversion of propionate carbon into citrate, whereas alpha-oxoglutarate increased formation of phosphoenolpyruvate. The fraction of metabolized propionate converted into phosphoenolpyruvate was about 17% in the presence or absence of alpha-oxoglutarate and about 7% in the presence of pyruvate. Pyruvate consumption was inhibited by 80% by 5mm-propionate. 2. Compared with rat liver, sheep liver was characterized by very high activities of phosphoenolpyruvate carboxykinase and moderately high activities of aconitase in the mitochondria and by low activities of ;malic' enzyme, pyruvate kinase and lactate dehydrogenase in the cytosol. Activities of phosphoenolpyruvate carboxy-kinase were similar in liver cytosol from rats and sheep. Activities of malate dehydrogenase and NADP-linked isocitrate dehydrogenase in sheep liver were about half those in rat liver. 3. The phosphate-dicarboxylate antiport was active in sheep liver mitochondria, but compared with rat liver mitochondria the citrate-malate antiport showed only low activity and mitochondrial aconitase was relatively inaccessible to external citrate. The rate of swelling of mitochondria induced by phosphate in solutions of ammonium malate was inversely related to the concentration of malate. 4. The results are discussed in relation to gluconeogenesis from propionate in sheep liver. It is proposed that propionate is converted into malate by the mitochondria and the malate is converted into phosphoenolpyruvate by enzymes in the cytosol. In this way sufficient NADH would be generated in the cytosol to convert the phosphoenolpyruvate into glucose.
D000818:Animals; D002951:Citrates / Q000096:biosynthesis; D003593:Cytoplasm / Q000201:enzymology; D003998:Dicarboxylic Acids / Q000378:metabolism; D005943:Gluconeogenesis; D005947:Glucose / Q000096:biosynthesis; D005977:Glutarates / Q000378:metabolism; D006836:Hydro-Lyases / Q000378:metabolism; D066298:In Vitro Techniques; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000378:metabolism; D008293:Malates / Q000096:biosynthesis / Q000378:metabolism; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009243:NAD / Q000096:biosynthesis; D009994:Osmolar Concentration; D010710:Phosphates / Q000494:pharmacology; D010728:Phosphoenolpyruvate / Q000096:biosynthesis* / Q000378:metabolism; D011422:Propionates / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D012756:Sheep; D013268:Stimulation, Chemical
D002951:Citrates; D003998:Dicarboxylic Acids; D005977:Glutarates; D008293:Malates; D010710:Phosphates; D011422:Propionates; D011773:Pyruvates; D009243:NAD; D010728:Phosphoenolpyruvate; D007770:L-Lactate Dehydrogenase; D008291:Malate Dehydrogenase; D007521:Isocitrate Dehydrogenase; D011770:Pyruvate Kinase; D006836:Hydro-Lyases; D005947:Glucose