STUDIES OF FATTY ACID OXIDATION: 4. THE EFFECTS OF FATTY ACIDS ON THE OXIDATION OF OTHER METABOLITES

1956 ◽  
Vol 34 (6) ◽  
pp. 1211-1225 ◽  
Author(s):  
P. G. Scholefield
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Respiratory Activity ◽  
Tricarboxylic Acid Cycle ◽  
Rat Kidney ◽  
Brain Mitochondria ◽  
Acid Oxidation ◽  
Inhibitory Effects ◽  
Kidney Mitochondria ◽  
Low Concentrations

Fatty acids inhibit the oxidation of pyruvate by rat-kidney mitochondria but the extent of inhibition depends upon the nature and amount of agent added to stimulate the oxidation. The longer chain fatty acids are more effective inhibitors and, in general, the even-numbered fatty acids show greater inhibitory effects than the adjacent odd-numbered fatty acids. Under conditions where 2, 4-dinitrophenol (DNOP) and the fatty acids separately have little effect on the respiratory activity of rat-kidney mitochondria with pyruvate as substrate, the addition of both fatty acid and DNOP results in an extensive inhibition. At low concentrations the fatty acids are oxidized by rat-kidney mitochondria but at concentrations of 10−3 M and higher they inhibit their own oxidation, the oxidation of pyruvate, and those of the acids of the tricarboxylic acid cycle. The oxidation of pyruvate by rat-brain mitochondria is insensitive to decanoate but both the fumarate- and DNOP-stimulated oxidations of pyruvate are sensitive to the presence of decanoate. In contrast, Nembutal inhibits both the oxidation of pyruvate alone and the fumarate-stimulated oxidation of pyruvate. Possible mechanisms for the observed inhibitory effects of fatty acids are discussed.

STUDIES OF FATTY ACID OXIDATION: 4. THE EFFECTS OF FATTY ACIDS ON THE OXIDATION OF OTHER METABOLITES

1956 ◽  
Vol 34 (1) ◽  
pp. 1211-1225
Author(s):  
P. G. Scholefield
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Respiratory Activity ◽  
Tricarboxylic Acid Cycle ◽  
Rat Kidney ◽  
Brain Mitochondria ◽  
Acid Oxidation ◽  
Inhibitory Effects ◽  
Kidney Mitochondria ◽  
Low Concentrations

Fatty acids inhibit the oxidation of pyruvate by rat-kidney mitochondria but the extent of inhibition depends upon the nature and amount of agent added to stimulate the oxidation. The longer chain fatty acids are more effective inhibitors and, in general, the even-numbered fatty acids show greater inhibitory effects than the adjacent odd-numbered fatty acids. Under conditions where 2, 4-dinitrophenol (DNOP) and the fatty acids separately have little effect on the respiratory activity of rat-kidney mitochondria with pyruvate as substrate, the addition of both fatty acid and DNOP results in an extensive inhibition. At low concentrations the fatty acids are oxidized by rat-kidney mitochondria but at concentrations of 10−3 M and higher they inhibit their own oxidation, the oxidation of pyruvate, and those of the acids of the tricarboxylic acid cycle. The oxidation of pyruvate by rat-brain mitochondria is insensitive to decanoate but both the fumarate- and DNOP-stimulated oxidations of pyruvate are sensitive to the presence of decanoate. In contrast, Nembutal inhibits both the oxidation of pyruvate alone and the fumarate-stimulated oxidation of pyruvate. Possible mechanisms for the observed inhibitory effects of fatty acids are discussed.

STUDIES OF FATTY ACID OXIDATION: 5. THE EFFECT OF DECANOIC ACID ON OXIDATIVE PHOSPHORYLATION

1956 ◽  
Vol 34 (1) ◽  
pp. 1227-1232 ◽  
Author(s):  
P. G. Scholefield
Keyword(s):  
Fatty Acid ◽  
Oxidative Phosphorylation ◽  
Rat Brain ◽  
Fatty Acid Oxidation ◽  
Rat Kidney ◽  
Atp Synthesis ◽  
Decanoic Acid ◽  
Brain Mitochondria ◽  
Acid Oxidation ◽  
Rat Brain Mitochondria

The effects of potassium decanoate on the phosphorylation associated with the oxidation of pyruvate by rat-kidney and rat-brain mitochondria have been investigated. The suggestion that these two processes may be uncoupled from each other in the presence of decanoate has been confirmed. Further, it has been shown that the decanoate-insensitive oxidation of pyruvate by rat-brain mitochondria, occurring in the absence of such stimulating agents as fumarate, is not associated with ATP synthesis. The fumarate-stimulated oxidation of pyruvate by rat-brain mitochondria, which is inhibited by decanoate, is associated with a phosphorylation process which is uncoupled by decanoate. When pyruvate oxidation by rat-kidney or by rat-brain mitochondria is uncoupled from phosphorylation, the extent of uncoupling is proportional to the amount of decanoate added.

scholarly journals Why does Brain Metabolism not Favor Burning of Fatty Acids to Provide Energy? - Reflections on Disadvantages of the Use of Free Fatty Acids as Fuel for Brain

2013 ◽  
Vol 33 (10) ◽  
pp. 1493-1499 ◽  
Author(s):  
Peter Schönfeld ◽  
Georg Reiser
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Brain Mitochondria ◽  
Neuronal Firing ◽  
Acid Oxidation ◽  
Nonesterified Fatty Acids ◽  
Atp Generation ◽  
Slow Passage ◽  
The Brain

It is puzzling that hydrogen-rich fatty acids are used only poorly as fuel in the brain. The long-standing belief that a slow passage of fatty acids across the blood–brain barrier might be the reason. However, this has been corrected by experimental results. Otherwise, accumulated nonesterified fatty acids or their activated derivatives could exert detrimental activities on mitochondria, which might trigger the mitochondrial route of apoptosis. Here, we draw attention to three particular problems: (1) ATP generation linked to β-oxidation of fatty acids demands more oxygen than glucose, thereby enhancing the risk for neurons to become hypoxic; (2) β-oxidation of fatty acids generates superoxide, which, taken together with the poor anti-oxidative defense in neurons, causes severe oxidative stress;(3) the rate of ATP generation based on adipose tissue-derived fatty acids is slower than that using blood glucose as fuel. Thus, in periods of extended continuous and rapid neuronal firing, fatty acid oxidation cannot guarantee rapid ATP generation in neurons. We conjecture that the disadvantages connected with using fatty acids as fuel have created evolutionary pressure on lowering the expression of the β-oxidation enzyme equipment in brain mitochondria to avoid extensive fatty acid oxidation and to favor glucose oxidation in brain.

scholarly journals Clinical manifestations and management of fatty acid oxidation disorders

2020 ◽  
Vol 21 (4) ◽  
pp. 479-493
Author(s):  
J. Lawrence Merritt ◽  
Erin MacLeod ◽  
Agnieszka Jurecka ◽  
Bryan Hainline
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Tricarboxylic Acid Cycle ◽  
Clinical Manifestations ◽  
Signs And Symptoms ◽  
High Energy ◽  
Acid Oxidation ◽  
Fatty Acid Oxidation Disorders ◽  
Organ Systems

Abstract Fatty acid oxidation disorders (FAOD) are a group of rare, autosomal recessive, metabolic disorders caused by variants of the genes for the enzymes and proteins involved in the transport and metabolism of fatty acids in the mitochondria. Those affected by FAOD are unable to convert fatty acids into tricarboxylic acid cycle intermediates such as acetyl-coenzyme A, resulting in decreased adenosine triphosphate and glucose for use as energy in a variety of high-energy–requiring organ systems. Signs and symptoms may manifest in infants but often also appear in adolescents or adults during times of increased metabolic demand, such as fasting, physiologic stress, and prolonged exercise. Patients with FAOD present with a highly heterogeneous clinical spectrum. The most common clinical presentations include hypoketotic hypoglycemia, liver dysfunction, cardiomyopathy, rhabdomyolysis, and skeletal myopathy, as well as peripheral neuropathy and retinopathy in some subtypes. Despite efforts to detect FAOD through newborn screening and manage patients early, symptom onset can be sudden and serious, even resulting in death. Therefore, it is critical to identify quickly and accurately the key signs and symptoms of patients with FAOD to manage metabolic decompensations and prevent serious comorbidities.

Unsaturated fatty acids inhibit ADP- arachidonate-induced platelet aggregation without affecting thromboxane synthesis

1986 ◽  
Vol 64 (9) ◽  
pp. 906-913 ◽  
Author(s):  
Ella Dratewka-Kos ◽  
D. O. Tinker ◽  
Brigitte Kindl
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Platelet Aggregation ◽  
Unsaturated Fatty Acids ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Fatty Acid Inhibition ◽  
Induced Aggregation ◽  
Protein Free Medium

The inhibitory effects of three cis-unsaturated C18 fatty acids (oleic, linoleic, and linolenic acids, sodium salts) on ADP- and sodium-arachidonate-induced aggregation of washed rabbit platelets were investigated. When the platelets were suspended in protein-free medium containing dextran, it was found that these fatty acids at very low concentrations (2–45 μM) were potent inhibitors of platelet responsiveness and the inhibitory effect occurred within seconds. The inhibition of ADP-induced aggregation was not affected by abolishing the activity of platelet cyclooxygenase using aspirin. Human serum albumin relieved the inhibition caused by fatty acids for both ADP- and arachidonate-induced aggregation. The inhibitory effect of fatty acids does not seem to be due to decreased thromboxane formation (except possibly in the case of linolenate), and the relief of fatty acid inhibition by albumin does not potentiate thromboxane B2 formation from exogenous arachidonate. It is suggested that the inhibitory effect of polyunsaturated fatty acids on platelet aggregation is specific and not related to a general surfactant effect, since inhibition occurs far below the critical micelle concentration of fatty acid soaps.

STUDIES OF FATTY ACID OXIDATION: 5. THE EFFECT OF DECANOIC ACID ON OXIDATIVE PHOSPHORYLATION

1956 ◽  
Vol 34 (6) ◽  
pp. 1227-1232 ◽  
Author(s):  
P. G. Scholefield
Keyword(s):  
Fatty Acid ◽  
Oxidative Phosphorylation ◽  
Rat Brain ◽  
Fatty Acid Oxidation ◽  
Rat Kidney ◽  
Atp Synthesis ◽  
Decanoic Acid ◽  
Brain Mitochondria ◽  
Acid Oxidation ◽  
Rat Brain Mitochondria

The effects of potassium decanoate on the phosphorylation associated with the oxidation of pyruvate by rat-kidney and rat-brain mitochondria have been investigated. The suggestion that these two processes may be uncoupled from each other in the presence of decanoate has been confirmed. Further, it has been shown that the decanoate-insensitive oxidation of pyruvate by rat-brain mitochondria, occurring in the absence of such stimulating agents as fumarate, is not associated with ATP synthesis. The fumarate-stimulated oxidation of pyruvate by rat-brain mitochondria, which is inhibited by decanoate, is associated with a phosphorylation process which is uncoupled by decanoate. When pyruvate oxidation by rat-kidney or by rat-brain mitochondria is uncoupled from phosphorylation, the extent of uncoupling is proportional to the amount of decanoate added.

scholarly journals Fatty acid oxidation participates of the survival to starvation, cell cycle progression and differentiation in the insect stages of Trypanosoma cruzi

2021 ◽  
Author(s):  
Rodolpho Ornitz Oliveira Souza ◽  
Flávia Silva Damasceno ◽  
Sabrina Marsiccobetre ◽  
Marc Biran ◽  
Gilson Murata ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Trypanosoma Cruzi ◽  
Cell Cycle Progression ◽  
De Novo ◽  
Tricarboxylic Acid Cycle ◽  
Complex Life Cycle ◽  
Acid Oxidation ◽  
Beta Oxidation ◽  
Cycle Progression

During its complex life cycle, Trypanosoma cruzi colonizes different niches in its insect and mammalian hosts. This characteristic determined the types of parasites that adapted to face challenging environmental cues. The primary environmental challenge, particularly in the insect stages, is poor nutrient availability. These T. cruzi stages could be exposed to fatty acids originating from the degradation of the perimicrovillar membrane. In this study, we revisit the metabolic fate of fatty acid breakdown in T. cruzi . Herein, we show that during parasite proliferation, the glucose concentration in the medium can regulate the fatty acid metabolism. At the stationary phase, the parasites fully oxidize fatty acids. [U- 14 C]-palmitate can be taken up from the medium, leading to CO 2 production via beta-oxidation. Lastly, we also show that fatty acids are degraded through beta-oxidation. Additionally, through beta-oxidation, electrons are fed directly to oxidative phosphorylation, and acetyl-CoA is supplied to the tricarboxylic acid cycle, which can be used to feed other anabolic pathways such as the de novo biosynthesis of fatty acids.

scholarly journals Mitochondrial Fission Governed by Drp1 Regulates Exogenous Fatty Acid Usage and Storage in Hela Cells

Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 322
Author(s):  
Jae-Eun Song ◽  
Tiago C. Alves ◽  
Bernardo Stutz ◽  
Matija Šestan-Peša ◽  
Nicole Kilian ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Lipid Droplets ◽  
Mitochondrial Fission ◽  
Acid Oxidation ◽  
Mitochondrial Morphology ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
And Storage

In the presence of high abundance of exogenous fatty acids, cells either store fatty acids in lipid droplets or oxidize them in mitochondria. In this study, we aimed to explore a novel and direct role of mitochondrial fission in lipid homeostasis in HeLa cells. We observed the association between mitochondrial morphology and lipid droplet accumulation in response to high exogenous fatty acids. We inhibited mitochondrial fission by silencing dynamin-related protein 1(DRP1) and observed the shift in fatty acid storage-usage balance. Inhibition of mitochondrial fission resulted in an increase in fatty acid content of lipid droplets and a decrease in mitochondrial fatty acid oxidation. Next, we overexpressed carnitine palmitoyltransferase-1 (CPT1), a key mitochondrial protein in fatty acid oxidation, to further examine the relationship between mitochondrial fatty acid usage and mitochondrial morphology. Mitochondrial fission plays a role in distributing exogenous fatty acids. CPT1A controlled the respiratory rate of mitochondrial fatty acid oxidation but did not cause a shift in the distribution of fatty acids between mitochondria and lipid droplets. Our data reveals a novel function for mitochondrial fission in balancing exogenous fatty acids between usage and storage, assigning a role for mitochondrial dynamics in control of intracellular fuel utilization and partitioning.

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