Regulatory function of pyruvate dehydrogenase and the mitochondrion in lipogenesis.
The activity of pyruvate dehydrogenase from freshly isolated mitochondria was shown to be dependent upon the nutritional and metabolic state of the animal prior to sacrifice, such that mitochondria from the livers of 48 hr starved, diabetic, or high fat fed rats had lower enzyme activity than normal, chow fed rats. The activity of pyruvate dehydrogenase and the rate of lipogenesis were shown to correlate to a certain extent when a reconstituted, cell free system consisting of 105,000 x g supernatant of rat liver and isolated mitochondria was used. This system was employed so that the role of the mitochondrion and pyruvate dehydrogenase in lipogenesis could be investigated. Dichloroacetate increased the activity of pyruvate dehydrogenase and increased the rate of lipogenesis, suggesting that the activity of pyruvate dehydrogenase is an important factor in determining the rate of lipogenesis in the reconstituted system. It was observed, however, that dichloroacetate was more effective in stimulating the activity of pyruvate dehydrogenase than the rate of lipogenesis when mitochondria from starved animals were used to reconstitute lipogenesis. Furthermore, the cytoplasmic adenosine triphosphate/adenosine diphosphate ratios and phosphorylation potentials (ATP/ADP x Pi) maintained in the reconstituted system by mitochondria isolated from starved animals were found to be significantly lower than those maintained by mitochondria isolated from chow fed animals. It is proposed that the lower "energy pressure" maintained in the reconstituted system by mitochondria isolated from starved animals severely limits lipogenesis at the ATP requiring steps of the process.
D000085:Acetates / Q000494:pharmacology; D000227:Adenine Nucleotides / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004041:Dietary Fats; D005227:Fatty Acids / Q000096:biosynthesis; D008055:Lipids / Q000096:biosynthesis*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000502:physiology*; D051381:Rats; D013217:Starvation / Q000378:metabolism*
D000085:Acetates; D000227:Adenine Nucleotides; D004041:Dietary Fats; D005227:Fatty Acids; D008055:Lipids; D010710:Phosphates; D011768:Pyruvate Dehydrogenase Complex; D009243:NAD; D009249:NADP; D000251:Adenosine Triphosphatases