Uncoupling activity of long-chian fatty acids

Borst, Piet; Loos, J.A.; Christ, E.J.; Slater, E.C.

doi:10.1016/0006-3002(62)90232-9

Cited by 293 publications

(92 citation statements)

References 32 publications

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“…The unmasking of the latent ATPase [cf. 21,22] at concentrations higher than about 50 nmoles palmitylcarnitine/mg protein is found similarly with palmitylCoA. It can be explained by increasing disruption of the inner membrane, due to the surface-active properties of both palmityl-esters.…”

Section: Resultsmentioning

confidence: 76%

Inhibition by fatty acyl esters of adenine nucleotide translocation in rat‐liver mitochondria

et al. 1972

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Section: Resultsmentioning

confidence: 76%

Inhibition by fatty acyl esters of adenine nucleotide translocation in rat‐liver mitochondria

et al. 1972

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“…Activation of pyruvate dehydrogenase by dichloroacetate (McAllister et al, 1973) stimulated also, but to a smaller amount, carbohydrate metabolism and showed an oxygen saving effect of 16%. A number of possibilities can be suggested to explain this greater decrease of oxygen uptake than expected by the increase of ATP/O ratio: ( I ) Because N EFA are known uncoupling agents of mitrochondrial oxidative phosphorylation in vitro (Borst et al, 1962), the large stimulation of respiration by NEFA in the isolated rat heart has been explained as a consequence of an uncoupling action (Challoner and Steinberg, 1966). Surface pyridine nucleotide fluorescense measurements in the isolated rat heart as described by Chance et al 1965) however showed no oxidation of the mitrochondrial pyridine nucleotides as the expected typical response to uncoupling agents (Pearce et al, 1979); ( 2 ) When the theoretical ATP/O ratio is maintained, there could be an ATP-consuming futile cycle such as long-chain fatty acyl-CoA formation and hydrolysis by fatty acyl hydrolases (Pearce et al, 1979).…”

Section: Discussionmentioning

confidence: 99%

Influence of Myocardial Substrate Utilization on the Oxygen Consumption of the Heart

Kahles

Hellige

Hunneman

et al. 1982

Clinical Cardiology

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Summary:The effect of changing myocardial metabolism from predominantly lipid to predominantly carbohydrate utilization on myocardial oxygen consumption ( MVOz) was studied in 10 closed-chest dogs. Oxygen saving potency df different metabolic interventions was quankified over a wide hernodynamic range by comparing the directly determined MVO2 with the hemodynamic parameter total left ventricular energy demand (El), which correlates closely under control conditions with MV02 (r = 0.98). Stimulation of carbohydrate metabolism by addition of glucose and /3-pyridyl carbinol or by activation of pyruvate dehydrogenase with dichloroacetate (DCA) shifted the cardiac respiratory quotient during @-stimulation from 0.73 to 1 .OO and 0.89, respectively, the nonesterified fatty acid/albumin ratio decreased from 4.0 to 0.5, or remained unchanged with DCA, and MVOz was reduced by 25 and 16%, respectively. Therapeutic approaches aimed at decreasing MV02 by changing substrate utilization are discussed.

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“…These differences could conceivably be caused by differences in the preparation of mitochondria or by differences in the amount of fat infiltration in the livers produced by different diets, which could contaminate the mitochondrial preparations. It is well known that some fatty acids are effective mitochondrial uncouplers (Borst et al, 1962;Lardy et al, 1965). Despite these differences it is clear that a mitochondrial uncoupling as measured in vitro is not a constant concomitant of chronic ethanol ingestion.…”

Section: Discussionmentioning

confidence: 99%

Metabolic alterations produced in the liver by chronic ethanol administration. Increased oxidative capacity

Videla

Bernstein

Israel

1973

Biochemical Journal

180

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1. Administration of ethanol (14g/day per kg) for 21-26 days to rats increases the ability of the animals to metabolize ethanol, without concomitant changes in the activities of liver alcohol dehydrogenase or catalase. 2. Liver slices from rats chronically treated with ethanol showed a significant increase (40-60%/) in the rate of 02 consumption over that of slices from control animals. The effect of uncoupling agents such as dinitrophenol and arsenate was completely lost after chronic treatment with ethanol. 3. Isolated mitochondria prepared from animals chronically treated with ethanol showed no changes in state 3 or state 4 respiration, ADP/O ratio, respiratory control ratio or in the dinitrophenol effect when succinate was used as substrate. With f-hydroxybutyrate as substrate a small but statistically significant decrease was found in the ADP/O ratio but not in the other parameters or in the dinitrophenol effect. Further, no changes in mitochondrial Mg2+-activated adenosine triphosphatase, dinitrophenol-activated adenosine triphosphatase or in the dinitrophenol-activated adenosine triphosphatase/Mg2+-activated adenosine triphosphatase ratio were found as a result of the chronic ethanol treatment. 4. Liver microsomal NADPH oxidase activity, a H202-producing system, was increased by 80-100 % by chronic ethanol treatment. Oxidation offormate to CO2 in vivo was also increased in these animals. The increase in formate metabolism could theoretically be accounted for by an increased production of H202 by the NADPH oxidase system plus formate peroxidation by catalase. However, an increased production of H202 and oxidation of ethanol by the catalase system could not account for more than 10-20% of the increased ethanol metabolism in the animals chronically treated with ethanol. 5. Results presented indicate that chronic ethanol ingestion results in a faster mitochondrial 02 consumption in situ suggesting a faster NADH reoxidation. Although only a minor change in mitochondrial coupling was observed with isolated mitochondria, the possibility of an uncoupling in the intact cell cannot be completely discarded. Regardless of the mechanism, these changes could lead to an increased metabolism of ethanol and of other endogenous substrates.Previous studies by our group (Videla & Israel, 1970) indicate that the rate of ethanol metabolism by the liver depends on the rate of mitochondrial reoxidation of the cytoplasmic NADH produced in the oxidation of ethanol. Uncoupling agents such as 2,4-dinitrophenol or arsenate were shown to increase markedly the rate of ethanol metabolism by normal rat liver slices. Dinitrophenol was also shown to be effective in increasing the rate of ethanol metabolism in vivo . However, although dinitrophenol increased the ethanol metabolism in liver slices from control animals, it was not effective in those from animals chronically treated with ethanol, in which the rate of ethanol metabolism had already been increased. This suggested that the rate ofethanol metabolism in these animals was no longer ...

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Uncoupling activity of long-chian fatty acids

Cited by 293 publications

References 32 publications

Inhibition by fatty acyl esters of adenine nucleotide translocation in rat‐liver mitochondria

Inhibition by fatty acyl esters of adenine nucleotide translocation in rat‐liver mitochondria

Influence of Myocardial Substrate Utilization on the Oxygen Consumption of the Heart

Metabolic alterations produced in the liver by chronic ethanol administration. Increased oxidative capacity

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