Reversal of mitochondrial swelling associated with fatty acid oxidation. II. Effects of cytochrome c and carnitine on contraction of fatty acid swollen mitochondria

1968 ◽  
Vol 46 (9) ◽  
pp. 1151-1160 ◽  
Author(s):  
Misako Nakatani ◽  
W. C. McMurray
Keyword(s):  
Fatty Acid ◽  
Cytochrome C ◽  
Energy Requirement ◽  
Liver Mitochondria ◽  
High Energy ◽  
Fatty Acyl ◽  
Water Soluble ◽  
Rat Liver Mitochondria ◽  
Acid Oxidation ◽  
Swelling Agent

Rat liver mitochondria undergo reversible swelling in the presence of a fatty acyl CoA generating system. Contraction of the swollen mitochondria was observed on the addition of either carnitine or cytochrome c. At low concentrations the two agents acted synergistically. At high concentrations cytochrome c completely replaced the requirement for carnitine.Cytochrome c also promoted the contraction of mitochondria swollen in the presence of fatty acid alone, provided that either ATP or ADP was added to initiate the contraction. The stimulation by cytochrome c was greater in the presence of ADP, and the contraction was more sensitive to respiratory inhibitors or dinitrophenol but was less sensitive to oligomycin than in the presence of ATP. Studies of the metabolism of 14C-labelled palmitate during cytochrome c induced contraction showed that decreases in mitochondrial-bound fatty acid and corresponding increases in water-soluble metabolites coincided with the reversal of swelling. The results indicated that the energy requirement for mitochondrial contraction in the presence of cytochrome c was provided by generation of high-energy intermediates coupled to oxidation of the fatty acid swelling agent.

scholarly journals Development of fatty acid oxidation in neonatal guinea-pig liver

1982 ◽  
Vol 208 (3) ◽  
pp. 723-730 ◽  
Author(s):  
D A Shipp ◽  
M Parameswaran ◽  
I J Arinze
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Guinea Pig ◽  
Ketone Bodies ◽  
Liver Mitochondria ◽  
Fatty Acyl ◽  
Acid Oxidation ◽  
Beta Oxidation ◽  
Pig Liver ◽  
Guinea Pig Liver

The capacity of foetal and neonatal liver to oxidize short-, medium- and long-chain fatty acids was studied in the guinea pig. Liver mitochondria from foetal and newborn animals were unable to synthesize ketone bodies from octanoate, but octanoylcarnitine and palmitoylcarnitine were readily ketogenic. The ketogenic capacity at 24 h after birth was as high as in adult animals. Hepatocytes isolated from term animals were unable to oxidize fatty acids, but at 6 h after birth production of 14CO2, acid-soluble products and acetoacetate from 1-14C-labelled fatty acids was 40-50% of the rates at 24 h. At 12 h of age these rates had already reached the 24 h values and did not change during suckling in the first week of life. The activities of hepatic fatty acyl-CoA synthetases, which were minimal in the foetus or at term, increased to maximal values in 12-24 h. The data show that the capacity for beta-oxidation and ketogenesis develops maximally in this species during the first 6-12 h after birth, and appears to be partly dependent on the development of fatty acid-activating enzyme.

Ammonium Chloride Inhibits Pyruvate Oxidation in Rat Liver Mitochondria: A Possible Cause of Fatty Liver in Reye's Syndrome and Urea Cycle Defects

1994 ◽  
Vol 87 (5) ◽  
pp. 499-503 ◽  
Author(s):  
Vaddanahally T. Maddaiah ◽  
Uday Kumbar
Keyword(s):  
Oxidative Metabolism ◽  
Urea Cycle ◽  
Tricarboxylic Acid Cycle ◽  
Liver Mitochondria ◽  
Fatty Acyl ◽  
Rat Liver Mitochondria ◽  
Acid Oxidation ◽  
Reye's Syndrome ◽  
Acetyl Coa ◽  
Total Oxidation

1. Earlier studies with liver slices showed that inhibition by NH+4 of the oxidation of palmitate to CO2 was greater than total oxidation, whereas salicylate exerted a stronger inhibitory effect on the latter. We have now investigated the effects of NH4Cl and salicylate on ADP-induced O2 consumption by mitochondria (State 3 rate) respiring on pyruvate, and oxidation of [1-14C]- and [2-14C]-pyruvate to14CO2. 2. The rate of State 3 respiration was inhibited and plateaued at 45% with 10 mmol/l NH4Cl. 3. Oxidation of [1-14C]pyruvate was not significantly affected by either NH4Cl or salicylate. Oxidation of [2-14C]pyruvate was strongly inhibited and plateaued at 70% with 1 mmol/1 NH4Cl (IC50 = 0.125 mmol/1). ADP (1 mmol/l) increased the rate of decarboxylation of [2-14C] pyruvate but the extent of NH4Cl inhibition was not affected. Salicylate had a slight activating effect in the absence or presence of NH4Cl. 4. These results indicate that NH4Cl inhibits the oxidative metabolism of acetyl-CoA in the tricarboxylic acid cycle. Therefore, inhibition of fatty acid oxidation to acetyl-CoA as well as its further oxidative metabolism occurring under hyperammonaemia (>0.1 mmol-1.49 mmol/l in Reye's syndrome patients) may be one of the causes of fatty acidaemia. 5. The cumulative inhibitory effects of NH+4 and fatty acyl derivatives on mitochondrial oxidative metabolism and production of ATP, as well as the uncoupling effects of salicylate, may contribute to some of the pathophysiology observed in patients with Reye's syndrome, and enzyme defects of the urea cycle.

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