scholarly journals Emodin and rhein in Cassia tora ameliorates activity of mitochondrial enzymes involved in oxidative phosphorylation in the retina of diabetic mice

2021 ◽  
Vol 64 (1) ◽  
Author(s):  
Eun Ko ◽  
Min Young Um ◽  
Taewon Han ◽  
Sooim Shin ◽  
Moonsung Choi

AbstractCassia tora is an annual herb, which has pharmacological effects such as antioxidant, hypolipidemic, and antidiabetic effects. Accordingly, its effect on diabetes has been well-studied. However, it is unclear whether it has an effect on mitochondrial dysfunction associated with diabetes. In this study, the effects of emodin and rhein in C. tora seed ethanolic extract (ER/CSEE) on retinal mitochondrial function were examined in high-fat diet (HFD)-fed mice. HFD-fed mice exhibited decreased mitochondrial function followed by compensatory increase in the expression levels of mitochondrial enzymes. However, ER/CSEE treatment for 12 weeks ameliorated the activity of retinal mitochondrial complexes and reduced the expression level of enzymes involved in oxidative phosphorylation, except that of complex II and citrate synthase in citric acid cycle. This suggests that repairing capacity of enzymes in electron transport chain and citric acid cycle of mitochondria are different in response to the metabolic state. Therefore, it concluded that emodin and rhein play a pharmacological role in fat metabolism by influencing activities of enzymes in citric acid cycle linked with beta-oxidation in retina.

1968 ◽  
Vol 108 (3) ◽  
pp. 413-415
Author(s):  
Eugene Goldwasser

The activities of the eight citric acid-cycle enzymes of rat bone-marrow cells were determined along with several other mitochondrial and non-mitochondrial enzymes. Four of the citric acid-cycle enzymes (aconitase, succinyl-CoA thiokinase, α-oxoglutarate dehydrogenase and succinate dehydrogenase) have closely similar low activities; two [isocitrate dehydrogenase (NAD) and citrate synthase] have intermediate activities; the remaining two (malate dehydrogenase and fumarase) have high activities. The other enzymes surveyed also exhibited a spread of three orders of magnitude, the mitochondrial enzymes showing no less variation than the others.


Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1410 ◽  
Author(s):  
Gerresheim ◽  
Roeb ◽  
Michel ◽  
Niepmann

Hepatitis C Virus (HCV) mainly infects liver hepatocytes and replicates its single-stranded plus strand RNA genome exclusively in the cytoplasm. Viral proteins and RNA interfere with the host cell immune response, allowing the virus to continue replication. Therefore, in about 70% of cases, the viral infection cannot be cleared by the immune system, but a chronic infection is established, often resulting in liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Induction of cancer in the host cells can be regarded to provide further advantages for ongoing virus replication. One adaptation in cancer cells is the enhancement of cellular carbohydrate flux in glycolysis with a reduction of the activity of the citric acid cycle and aerobic oxidative phosphorylation. To this end, HCV downregulates the expression of mitochondrial oxidative phosphorylation complex core subunits quite early after infection. This so-called aerobic glycolysis is known as the “Warburg Effect” and serves to provide more anabolic metabolites upstream of the citric acid cycle, such as amino acids, pentoses and NADPH for cancer cell growth. In addition, HCV deregulates signaling pathways like those of TNF-β and MAPK by direct and indirect mechanisms, which can lead to fibrosis and HCC.


1976 ◽  
Vol 154 (3) ◽  
pp. 689-700 ◽  
Author(s):  
P R. Alp ◽  
E A. Newsholme ◽  
V A. Zammit

1. The activities of citrate synthase, NAD+-linked and NADP+-linked isocitrate dehydrogenase were measured in muscles from a large number of animals, in order to provide some indication of the importance of the citric acid cycle in these muscles. According to the differences in enzyme activities, the muscles can be divided into three classes. First, in a number of both vertebrate and invertebrate muscles, the activities of all three enzymes are very low. It is suggested that either the muscles use energy at a very low rate or they rely largely on anaerobic glycolysis for higher rates of energy formation. Second, most insect flight muscles contain high activities of citrate synthase and NAD+-linked isocitrate dehydrogenase, but the activities of the NADP+-linked enzyme are very low. The high activities indicate the dependence of insect flight on energy generated via the citric acid cycle. The flight muscles of the beetles investigated contain high activities of both isocitrate dehydrogenases. Third, other muscles of both vertebrates and invertebrates contain high activities of citrate synthase and NADP+-liniked isocitrate dehydrogenase. Many, if not all, of these muscles are capable of sustained periods of mechanical activity (e.g. heart muscle, pectoral muscles of some birds). Consequently, to support this activity fuel must be supplied continually to the muscle via the circulatory system which, in most animals, also transports oxygen so that energy can be generated by complete oxidation of the fuel. It is suggested that the low activities of NAD+-linked isocitrate dehydrogenase in these muscles may be involved in oxidation of isocitrate in the cycle when the muscles are at rest. 2. A comparison of the maximal activities of the enzymes with the maximal flux through the cycle suggests that, in insect flight muscle, NAD+-linked isocitrate dehydrogenase catalyses a non-equilibrium reaction and citrate synthease catalyses a near-equilibrium reaction. In other muscles, the enzyme-activity data suggest that both citrate synthase and the isocitrate dehydrogenase reactions are near-equilibrium.


2006 ◽  
Vol 188 (12) ◽  
pp. 4350-4355 ◽  
Author(s):  
Yajing Hu ◽  
James F. Holden

ABSTRACT The hyperthermophilic archaeon Pyrobaculum islandicum uses the citric acid cycle in the oxidative and reductive directions for heterotrophic and autotrophic growth, respectively, but the control of carbon flow is poorly understood. P. islandicum was grown at 95°C autotrophically, heterotrophically, and mixotrophically with acetate, H2, and small amounts of yeast extract and with thiosulfate as the terminal electron acceptor. The autotrophic growth rates and maximum concentrations of cells were significantly lower than those in other media. The growth rates on H2 and 0.001% yeast extract with and without 0.05% acetate were the same, but the maximum concentration of cells was fourfold higher with acetate. There was no growth with acetate if 0.001% yeast extract was not present, and addition of H2 to acetate-containing medium greatly increased the growth rates and maximum concentrations of cells. P. islandicum cultures assimilated 14C-labeled acetate in the presence of H2 and yeast extract with an efficiency of 55%. The activities of 11 of 19 enzymes involved in the central metabolism of P. islandicum were regulated under the three different growth conditions. Pyruvate synthase and acetate:coenzyme A (CoA) ligase (ADP-forming) activities were detected only in heterotrophically grown cultures. Citrate synthase activity decreased in autotrophic and acetate-containing cultures compared to the activity in heterotrophic cultures. Acetylated citrate lyase, acetate:CoA ligase (AMP forming), and phosphoenolpyruvate carboxylase activities increased in autotrophic and acetate-containing cultures. Citrate lyase activity was higher than ATP citrate synthase activity in autotrophic cultures. These data suggest that citrate lyase and AMP-forming acetate:CoA ligase, but not ATP citrate synthase, work opposite citrate synthase to control the direction of carbon flow in the citric acid cycle.


2021 ◽  
Vol 22 (2) ◽  
pp. 604
Author(s):  
Dirk Roosterman ◽  
Graeme Stuart Cottrell

In 1937, Sir H. A Krebs first published the Citric Acid Cycle, a unidirectional cycle with carboxylic acids. The original concept of the Citric Acid Cycle from Krebs’ 1953 Nobel Prize lecture illustrates the unidirectional degradation of lactic acid to water, carbon dioxide and hydrogen. Here, we add the heart lactate dehydrogenase•proton-linked monocarboxylate transporter 1 complex, connecting the original Citric Acid Cycle to the flow of energy and material. The heart lactate dehydrogenase•proton-linked monocarboxylate transporter 1 complex catalyses the first reaction of the Citric Acid Cycle, the oxidation of lactate to pyruvate, and thus secures the provision of pyruvic acid. In addition, we modify Krebs’ original concept by feeding the cycle with oxaloacetic acid. Our concept enables the integration of anabolic processes and allows adaption of the organism to recover ATP faster.


Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1068 ◽  
Author(s):  
Joséphine Zangari ◽  
Francesco Petrelli ◽  
Benoît Maillot ◽  
Jean-Claude Martinou

Pyruvate, the end product of glycolysis, plays a major role in cell metabolism. Produced in the cytosol, it is oxidized in the mitochondria where it fuels the citric acid cycle and boosts oxidative phosphorylation. Its sole entry point into mitochondria is through the recently identified mitochondrial pyruvate carrier (MPC). In this review, we report the latest findings on the physiology of the MPC and we discuss how a dysfunctional MPC can lead to diverse pathologies, including neurodegenerative diseases, metabolic disorders, and cancer.


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