scholarly journals Biochemical effects of the hypoglycaemic compound pent-4-enoic acid and related non-hypoglycaemic fatty acids. Oxidative phosphorylation and mitochondrial oxidation of pyruvate, 3-hydroxybutyrate and tricarboxylic acid-cycle intermediates

1968 ◽  
Vol 110 (3) ◽  
pp. 499-509 ◽  
Author(s):  
A. E. Senior ◽  
H. S. A. Sherratt
Keyword(s):  
Oxidative Phosphorylation ◽  
Tricarboxylic Acid Cycle ◽  
Time Lag ◽  
Liver Mitochondria ◽  
Enoic Acid ◽  
Rat Liver Mitochondria ◽  
Pentanoic Acid ◽  
Low Concentrations ◽  
Cyclobutanecarboxylic Acid ◽  
Tricarboxylic Acid Cycle Intermediates

1. The effects of the hypoglycaemic compound pent-4-enoic acid, and of four structurally related non-hypoglycaemic compounds (pent-2-enoic acid, pentanoic acid, cyclopropanecarboxylic acid and cyclobutanecarboxylic acid), on several reactions in rat liver mitochondria were determined. 2. The use of manometric techniques for measurements of oxidations and of phosphorylation is critically discussed. 3. Pent-4-enoic acid and pentanoic acid uncoupled oxidative phosphorylation at low concentrations, but usually by not more than about 50%. 4. All the compounds, except cyclobutanecarboxylic acid, strongly inhibited the oxidation of pyruvate and 2-oxoglutarate, but the oxidations of succinate, citrate and 3-hydroxybutyrate were not strongly inhibited. 5. All the compounds, except cyclobutanecarboxylic acid, inhibited decarboxylation of [1−14C]pyruvate with ferricyanide as electron acceptor. 6. All the compounds, except pent-2-enoic acid, caused mitochondrial swelling after a time-lag.

scholarly journals A spectrophotometric procedure for rapid and sensitive measurements of β-oxidation. Demonstration of factors that can be rate-limiting for β-oxidation

1977 ◽  
Vol 164 (3) ◽  
pp. 621-633 ◽  
Author(s):  
H Osmundsen ◽  
J Bremer
Keyword(s):  
Tricarboxylic Acid Cycle ◽  
Liver Mitochondria ◽  
Heart Mitochondria ◽  
Rat Liver Mitochondria ◽  
Beta Oxidation ◽  
Direct Reading ◽  
Kidney Mitochondria ◽  
Final Electron ◽  
Acyl Coa Dehydrogenases ◽  
Tricarboxylic Acid Cycle Intermediates

1. A spectrophotometric direct-reading assay for measurements of beta-oxidation by intact mitochondria is described. The procedure relies on the ability of ferricyanide to trap reducing equivalents generated by the acyl-CoA dehydrogenases (EC 1.3.99.3). The reduction of ferricyanide was recorded by using a dual-wavelength spectrophotometer. 2. Oxaloacetate or acetoacetate was used to stimulate the rate of beta-oxidation by rotenone-blocked mitochondria. Although both were effective with rat liver mitochondria, oxaloacetate gave about 75% more stimulation. With heart or kidney mitochondria, only oxaloacetate gave marked stimulation. Acetoacetate had no stimulatory effect with heart mitochondria, but a small stimulatory effect on the rate of beta-oxidation by kidney mitochondria. 3. The stoicheiometry of beta-oxidation-dependent reduction of ferricyanide was examined, and good correlations were found between experimental and theoretical amounts of ferricyanide reduced. 4. Ferricyanide appears as efficient a final electron acceptor as O2. With ferricyanide the rate of beta-oxidation by heart mitochondria can be measured without interference from the oxidation of tricarboxylic acid-cycle intermediates.

scholarly journals Biochemical effects of the hypoglycaemic compound pent-4-enoic acid and related non-hypoglycaemic fatty acids. Carbohydrate metabolism

1968 ◽  
Vol 110 (3) ◽  
pp. 521-527 ◽  
Author(s):  
A. E. Senior ◽  
H. S. A. Sherratt
Keyword(s):  
Rat Liver ◽  
Rat Kidney ◽  
Enoic Acid ◽  
Rat Tissues ◽  
Pentanoic Acid ◽  
Kidney Slices ◽  
Biochemical Effects ◽  
Low Concentrations ◽  
Cyclopropanecarboxylic Acid ◽  
Cyclobutanecarboxylic Acid

1. The effects of the hypoglycaemic compound, pent-4-enoic acid, and of four structurally related non-hypoglycaemic compounds (pent-2-enoic acid, pentanoic acid, cyclopropanecarboxylic acid and cyclobutanecarboxylic acid), on glycolysis, glucose oxidation and gluconeogenesis in some rat tissues were determined. 2. None of the compounds at low concentrations inhibited glycolysis by particle-free supernatant fractions from rat liver, skeletal muscle and intestinal mucosa, though there was inhibition by cyclopropanecarboxylic acid and cyclobutanecarboxylic acid at 3mm concentration. 3. Pent-4-enoic inhibited the oxidation of [1−14C]palmitate by rat liver slices, but did not increase the oxidation of [U−14C]glucose. 4. Pent-4-enoic acid (0·01mm) strongly inhibited gluconeogenesis by rat kidney slices from pyruvate or succinate, but none of the other compounds inhibited significantly at low concentrations. 5. There was also some inhibition of gluconeogenesis in kidney slices from rats injected with pent-4-enoic acid. 6. The mechanism of the hypoglycaemic effect of pent-4-enoic acid is discussed; it is suggested that there is an inhibition of fatty acid and ketone-body oxidation and of gluconeogenesis so that glucose reserves become exhausted, leading to hypoglycaemia. 7. The mechanism of the hypoglycaemic action of pent-4-enoic acid appears to be similar to that of hypoglycin.

scholarly journals Oxidative phosphorylation. The specific binding of trimethyltin and triethyltin to rat liver mitochondria

1970 ◽  
Vol 118 (1) ◽  
pp. 171-179 ◽  
Author(s):  
W. N. Aldridge ◽  
B. W. Street
Keyword(s):  
Adipose Tissue ◽  
Oxidative Phosphorylation ◽  
Brown Adipose Tissue ◽  
Binding Site ◽  
Rat Liver ◽  
Specific Binding ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Affinity Constants ◽  
Brown Adipose

1. The binding of trimethyltin and triethyltin to rat liver mitochondria was determined and the results were analysed by the method of Scatchard (1949). 2. One binding site (site 1) has the correct characteristics for the site to which trimethyltin and triethyltin are attached when they inhibit oxidative phosphorylation. For each compound the concentration of site 1 is 0.8nmol/mg of protein and the ratios of their affinity constants are the same as the ratio of the concentrations inhibiting oxidative phosphorylation. 3. Binding site 1 is present in a fraction derived from mitochondria containing only 15% of the original protein. In this preparation ultrasonication rapidly destroyed site 1. 4. Dimethyltin and diethyltin do not prevent binding of triethyltin to rat liver mitochondria, whereas triethyl-lead does. 5. Trimethyltin and triethyltin bind to mitochondria from brown adipose tissue and the results indicate a binding site 1 similar to that in rat liver mitochondria. 6. The advantages and limitations of this approach to the study of inhibitors are discussed.

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