scholarly journals Logical modelling reveals the PDC-PDK interaction as the regulatory switch driving metabolic flexibility at the cellular level

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Samar HK Tareen ◽  
Martina Kutmon ◽  
Ilja CW Arts ◽  
Theo M de Kok ◽  
Chris T Evelo ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Pyruvate Dehydrogenase ◽  
Tricarboxylic Acid Cycle ◽  
Pyruvate Dehydrogenase Complex ◽  
Tricarboxylic Acid ◽  
Cellular Level ◽  
Acid Oxidation ◽  
Metabolic Flexibility ◽  
Acid Cycle

Abstract Background Metabolic flexibility is the ability of an organism to switch between substrates for energy metabolism, in response to the changing nutritional state and needs of the organism. On the cellular level, metabolic flexibility revolves around the tricarboxylic acid cycle by switching acetyl coenzyme A production from glucose to fatty acids and vice versa. In this study, we modelled cellular metabolic flexibility by constructing a logical model connecting glycolysis, fatty acid oxidation, fatty acid synthesis and the tricarboxylic acid cycle, and then using network analysis to study the behaviours of the model. Results We observed that the substrate switching usually occurs through the inhibition of pyruvate dehydrogenase complex (PDC) by pyruvate dehydrogenase kinases (PDK), which moves the metabolism from glycolysis to fatty acid oxidation. Furthermore, we were able to verify four different regulatory models of PDK to contain known biological observations, leading to the biological plausibility of all four models across different cells and conditions. Conclusion These results suggest that the cellular metabolic flexibility depends upon the PDC-PDK regulatory interaction as a key regulatory switch for changing metabolic substrates.

scholarly journals Detection of myocardial medium‐chain fatty acid oxidation and tricarboxylic acid cycle activity with hyperpolarized [1– 13 C]octanoate

2020 ◽  
Vol 33 (3) ◽  
Author(s):  
Hikari A.I. Yoshihara ◽  
Jessica A.M. Bastiaansen ◽  
Magnus Karlsson ◽  
Mathilde H. Lerche ◽  
Arnaud Comment ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Chain Fatty Acid ◽  
Medium Chain Fatty Acid ◽  
Acid Oxidation ◽  
Acid Cycle ◽  
Medium Chain

UTILIZATION OF LIPIDS BY FISH: II. FATTY ACID OXIDATION BY A PARTICULATE FRACTION FROM LATERAL LINE MUSCLE

1964 ◽  
Vol 42 (3) ◽  
pp. 345-352 ◽  
Author(s):  
E. Bilinski ◽  
R. E. E. Jonas
Keyword(s):  
Fatty Acid ◽  
Rainbow Trout ◽  
Fatty Acid Oxidation ◽  
Lateral Line ◽  
Sockeye Salmon ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Acid Oxidation ◽  
Acid Cycle ◽  
Tricarboxylic Acid Cycle Intermediates

The fatty acid oxidizing system present in lateral line muscle of rainbow trout (Salmo gairdnerii) and sockeye salmon (Oncorhynchus nerka) was studied by using subcellular particles, having the sedimentation characteristics of mitochondria. The rate of oxidation of K-myristate-1-C14, K-octanoate-1-C14, and Na-hexanoate-1-C14 was determined at 25 °C by measuring the formation of C14O2. Oxidation was stimulated by adenosine triphosphate Mg++, coenzyme A and tricarboxylic acid cycle intermediates, but not by cytochrome c. It was optimum at pH 7.5–8.5.The data are consistent with the assumption that in the lateral line muscle fatty acid oxidation takes place through the known mechanism involving CoA derivatives.

scholarly journals Gene expression analysis in mitochondria from chagasic mice: alterations in specific metabolic pathways

2004 ◽  
Vol 381 (3) ◽  
pp. 743-752 ◽  
Author(s):  
Nisha GARG ◽  
Arpad GERSTNER ◽  
Vandanajay BHATIA ◽  
James DeFORD ◽  
John PAPACONSTANTINOU
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Mitochondrial Function ◽  
Pyruvate Dehydrogenase ◽  
Acid Metabolism ◽  
Tricarboxylic Acid Cycle ◽  
Pyruvate Dehydrogenase Complex ◽  
Tricarboxylic Acid ◽  
Acid Cycle ◽  
Dehydrogenase Complex

Cardiac hypertrophy and remodelling in chagasic disease might be associated with mitochondrial dysfunction. In the present study, we characterized the cardiac metabolic responses to Trypanosoma cruzi infection and progressive disease severity using a custom-designed mitoarray (mitochondrial function-related gene array). Mitoarrays consisting of known, well-characterized mitochondrial function-related cDNAs were hybridized with 32P-labelled cDNA probes generated from the myocardium of mice during immediate early, acute and chronic phases of infection and disease development. The mitoarray successfully identified novel aspects of the T. cruzi-induced alterations in the expression of the genes related to mitochondrial function and biogenesis that were further confirmed by real-time reverse transcriptase–PCRs. Of note is the up-regulation of transcripts essential for fatty acid metabolism associated with repression of the mRNAs for pyruvate dehydrogenase complex in infected hearts. We observed no statistically significant changes in mRNAs for the enzymes of tricarboxylic acid cycle. These results suggest that fatty acid metabolism compensates the pyruvate dehydrogenase complex deficiencies for the supply of acetyl-CoA for a tricarboxylic acid cycle, and chagasic hearts may not be limited in reduced energy (NADH and FADH2). The observation of a decrease in mRNA level for several subunits of the respiratory chain complexes by mitoarray as well as global genome analysis suggests a limitation in mitochondrial oxidative phosphorylation-mediated ATP-generation capacity as the probable basis for cardiac homoeostasis in chagasic disease.

Biochemical studies on ovine pregnancy toxaemia. I. Enzymic activities of liver and brain

1959 ◽  
Vol 10 (6) ◽  
pp. 854 ◽  
Author(s):  
CH Gallagher
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Tricarboxylic Acid Cycle ◽  
Liver Mitochondria ◽  
Tricarboxylic Acid ◽  
Acid Oxidation ◽  
Enzyme Preparations ◽  
Acid Cycle ◽  
Sheep Liver ◽  
Pregnancy Toxaemia

Enzymic activities in vitro of liver and brain tissue of sheep with pregnancy toxaemia were measured. Anaerobic glycolysis and oxidations of tricarboxylic acid cycle intermediates and related substrates were normal for both brain and liver enzyme preparations. Fatty acid oxidation by liver mitochondria was abnormal. Liver mitochondria from cases of pregnancy toxaemia were invariably incapable of oxidizing octanoate and palmitate, and frequently unable to oxidize propionate. The rate of propionate oxidation was low even when this substrate was oxidized. Butyrate oxidation was not much reduced by pregnancy toxaemia. Starvation of ewes in late pregnancy did not inactivate the fatty acid oxidation chains of liver mitochondria. Possible reasons for the failure of lipid metabolism are discussed. The dependence of sheep liver metabolism upon fatty acid oxidation is discussed. Insignificant amounts of glucose are absorbed from the alimentary canal in sheep and, even if absorbed, are not catabolized to supply acetyl coenzyme A for oxidation in the tricarboxylic acid cycle. Consequently sheep liver is prone to failure from interference with fatty acid oxidation. Pregnancy toxaemia is discussed in relevance to the disturbance of fatty acid metabolism which is thought to be of considerable significance in the disease.

scholarly journals Plasma acylcarnitine profiling indicates increased fatty acid oxidation relative to tricarboxylic acid cycle capacity in young, healthy low birth weight men

2016 ◽  
Vol 4 (19) ◽  
pp. e12977 ◽  
Author(s):  
Amalie Ribel-Madsen ◽  
Rasmus Ribel-Madsen ◽  
Charlotte Brøns ◽  
Christopher B. Newgard ◽  
Allan A. Vaag ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Fatty Acid Oxidation ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Acid Oxidation ◽  
Acid Cycle

Effect of experimental dysthyroidism on the enzymatic character of the diaphragm

1984 ◽  
Vol 56 (1) ◽  
pp. 117-121 ◽  
Author(s):  
C. D. Ianuzzo ◽  
V. Chen ◽  
P. O'Brien ◽  
T. G. Keens
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Fiber Type ◽  
Tricarboxylic Acid Cycle ◽  
Minute Ventilation ◽  
Tricarboxylic Acid ◽  
Albino Rats ◽  
Acid Oxidation ◽  
Fiber Types ◽  
Acid Cycle

This study examined the effects of long-term experimental dysthyroidism on the enzymatic character of the costal diaphragm and selected respiratory parameters. Costal diaphragms from thyroidectomized (TX), euthyroid (EU), and hyperthyroid (HT) male albino rats were used. HT was induced by subcutaneous injections of triiodothyronine on alternate days for 6 wk. Minute ventilation was greater for the HT (70%) compared with the TX rats. The enzymatic potentials of glycolysis (28%), tricarboxylic acid cycle (30%), and fatty acid oxidation (16%) were significantly increased in the HT diaphragms, whereas the potentials were lower by a similar relative extent in the TX diaphragms. The proportion of alkali-labile fibers were greater in the TX and lower in the HT diaphragm. The shifts in heart and muscle lactate dehydrogenase isoenzyme activities were consistent with the fiber type changes. These findings show that dysthyroidism modifies the overall enzymatic capacity of the diaphragm (i.e., glycolysis, tricarboxylic acid cycle, and fatty acid oxidation) along with the proportion of alkali-labile to alkali-stable fiber types. These enzymatic changes are similar to those resulting from exercise training, tracheal banding, streptozotocin diabetes, and emphysema.

Ontogeny of pyruvate dehydrogenase complex and key enzymes involved in glycolysis and tricarboxylic acid cycle in rabbit fetal lung, heart, and liver

1990 ◽  
Vol 68 (10) ◽  
pp. 1210-1217 ◽  
Author(s):  
Bhagu R. Bhavnani ◽  
Duncan G. Wallace
Keyword(s):  
Pyruvate Kinase ◽  
Pyruvate Dehydrogenase ◽  
Fetal Liver ◽  
Tricarboxylic Acid Cycle ◽  
Pyruvate Dehydrogenase Complex ◽  
Fetal Lung ◽  
Tricarboxylic Acid ◽  
Acid Cycle ◽  
Key Enzymes ◽  
Dehydrogenase Complex

The metabolic pathways by which the glycogen is utilized by fetal tissues is not well established. In the present study the ontogeny of seven key enzymes involved in glycolysis and the tricarboxylic acid cycle has been established for rabbit fetal lung, heart, and liver. In the fetal lung the activities of phosphofructokinase, pyruvate kinase, lactic dehydrogenase, citrate synthase, and malate dehydrogenase increase from day 21 to 25. Thereafter the levels either drop to day 19 levels or do not change. The isocitrate dehydrogenase activity continues to increase from day 19 of gestation to maximum level on day 31 of gestation. In fetal heart the pattern of activity is similar, but in fetal liver most of the enzymes reach maximum levels earlier and, with the exception of pyruvate kinase, do not show a significant fall in activity near term. The pattern of development of pyruvate dehydrogenase complex is different; maximum activity is observed on day 27 in fetal lung and heart and on day 21 in fetal liver. These results indicate that all three fetal tissues can oxidize glucose. Also, the accumulation of glycogen, particularly in fetal lung, appears to ensure that at specific times during gestation adequate quantities of energy (ATP) and substrates, required for surfactant phospholipid synthesis, are available independent of maternal supply of glucose or during brief episodes of hypoxia.Key words: glycogen, glycolysis, tricarboxylic acid cycle, pyruvate dehydrogenase, surfactant.

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