Effects of fasting on the control of fatty-acid synthesis in hepatoma 7777 and host liver. Role of long-chain fatty acyl-CoA,, the mitochondrial citrate transporter and pyruvate dehydrogenase activity.
The effects of fasting on the rate of fatty acid synthesis, the properties of the mitochondrial citrate transporter and on pyruvate dehydrogenase activity were investigated in "poorly-differentiated" tmorris hepatoma 7777 and in host liver preparations. The properties of the citrate transporter from hepatoma mitochondria were similar to those of host liver mitochondria, with the exception that the Km for the liver mitochondrial citrate transporter was 248 plus or minus 20 mu M while that in hepatoma mitochondria was less than 75 mu M. The acid-insoluble CoA content was 180 plus or minus 20 pmol/mg protein in the hepatoma and remained essentially unchanged in the fasted state, while the acid-insoluble CoA levels in livers from fed rats was 720 plus or minus 80 pmol/mg protein and were increased to 1050 plus or minus 50 pmol/mg protein during fasting. After a 36-h fast, the rate of lipogenesis and the percentage of pyruvate dehydrogenase present in the active form were each decreased by approximately 80% in host liver preparations. In contrast, the rate of lipogenesis by hepatoma slices did not decrease during fasting, and essentially all pyruvate dehydrogenase present was in the active form of hepatomas obtained from either fed or fasted animals. Implications concerning the identification of possible regulatory sites in the control of lipogenesis were discussed in relation to the above observations.
D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002250:Carbon Radioisotopes; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002951:Citrates / Q000378:metabolism*; D003065:Coenzyme A / Q000031:analogs & derivatives* / Q000032:analysis; D005215:Fasting; D005227:Fatty Acids / Q000096:biosynthesis*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D009374:Neoplasms, Experimental; D010169:Palmitic Acids; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D014233:Tricarboxylic Acids / Q000494:pharmacology
D002250:Carbon Radioisotopes; D002951:Citrates; D005227:Fatty Acids; D010169:Palmitic Acids; D011768:Pyruvate Dehydrogenase Complex; D014233:Tricarboxylic Acids; D000105:Acetyl Coenzyme A; D000255:Adenosine Triphosphate; D003065:Coenzyme A