Defects in citric acid cycle and the electron transport chain in progressive poliodystrophy

2009 ◽  
Vol 70 (3) ◽  
pp. 145-154 ◽  
Author(s):  
F. J. M. Gabreëls ◽  
M. J. J. Prick ◽  
J. M. F. Trijbels ◽  
W. O. Renier ◽  
H. H. J. Jaspar ◽  
...  
Author(s):  
Kanu Shil ◽  
Sudipta Pal

Objective: This study was conducted to observe the dose-dependent effect of Cr (VI) on certain aspects of carbohydrate metabolism in mice with four different doses, viz., 5 mg/kg, 10 mg/kg, 15 mg/kg and 20 mg/kg b.w., respectively, for 30 days of exposure.Methods: Blood glucose, glycogen content, and pyruvic acid of liver tissue were determined to evaluate the glycolytic activity. Enzymes such as isocitrate dehydrogenase (IDH), succinate dehydrogenase, and malate dehydrogenase (MDH) activities were measured to determine the tricarboxylic acid cycle function. In addition, nicotinamide adenine dinucleotide (NADH) ubiquinone C oxidoreductase activity was estimated to evaluate the alteration in oxidative phosphorylation pathway with dose-dependent chromium exposure. Total protein, free amino acid nitrogen, and transaminase enzyme activity were also measured.Results: Chromium exposure caused marked depletion of blood glucose and liver glycogen contents in a dose-dependent manner. The activities of IDH, succinate dehydrogenase, and MDH were significantly altered in a dose-specific manner by chromium exposure. Relevant exhaustion of glycolytic substrates was noted in the form of reduced pyruvate content in hepatocytes following chromium exposure. In addition, the treatment caused elevation of free amino nitrogen associated with depletion of total protein content and elevated transaminase enzyme activities in hepatocytes. Significant alteration of mitochondrial NADH-ubiquinone C oxidoreductase activity was also noted.Conclusion: By analyzing the observed results, it can be suggested that Cr (VI) exerts hypoglycemic and glycogenolytic effects associated with alteration of citric acid cycle and electron transport pathways in hepatocytes in a dose-specific manner thus resulting in serious alteration in the carbohydrate bioenergetics and mitochondrial energy generation in hepatic cells.Keywords: Hexavalent chromium, Hypoglycemia, Glycogenolysis, Citric acid cycle, Electron transport chain. 


2021 ◽  
Author(s):  
Qingying Li ◽  
Sujuan Guo ◽  
Chengshun Yang ◽  
Xueqing Liu ◽  
Xuemei Chen ◽  
...  

Abstract Background: Obesity is associated with many adverse effects on female fertility. Obese women are more likely to have ovulatory dysfunction due to dysregulation of the hypothalamic-pituitary-ovarian axis. However, ovarian function in obese women during early pregnancy still needs further assessment. Methods: Obesity was induced in C57BL6/J mice using high-fat diets (HFD) for 12 weeks; In vitro high-fat model was established with KGN cells treated with Oleate acid and Palmitic acid. Ovarian morphology of obese mice in early pregnancy was assessed by Hematoxylin and Eosin staining and its function was assessed using ELISA, Western blotting and Immunohistochemistry. The Oil Red O staining and Transmission electron microscopy were used to detect fatty acid accumulation and specific markers relating to ovarian functional mechanism were assessed by Real time PCR, Western blotting, Lactate detection, ATP detection, Biochemical analyses and ELISA.Results: The results of this study showed that during early pregnancy, the number of corpus luteum, serum estradiol and progesterone levels, and the expression of genes CYP19A1, CYP11A1 and StAR, which are related to steroid biosynthesis, were significantly increased in HFD female mice. HFD-fed mice also showed a significant increase in ovarian lipid accumulation on day 7 of pregnancy. Genes involved in fatty acid synthesis (Acsl4 and Elovl5) and fatty acid uptake and transport (Slc27a4), together with the β-oxidation rate-limiting enzyme (Cpt1a) were significantly upregulated in HFD-fed mice. Specifically, there was abnormal elevation of ATP level and aberrant expression of tricarboxylic acid cycle (TCA) and electron transport chain related genes in the ovary of HFD pregnant mice. Treatment of KGN cells with etomoxir targeting β-oxidation of fatty acid, showed decrease tricarboxylic acid cycle and electron transport chain. The elevated ATP level and the increased estradiol and progesterone levels were reversed. Conclusions: This study indicated that during early pregnancy, high-fat diet and induced-obesity increased fatty acid β-oxidation, which in turn increase the tricarboxylic acid cycle and the electron transport chain, and consequently increases ATP production and ovarian dysfunction.


1988 ◽  
Vol 66 (10) ◽  
pp. 2083-2097 ◽  
Author(s):  
David H. Turpin ◽  
Ivor R. Elrifi ◽  
Douglas G. Birch ◽  
Harold G. Weger ◽  
Jody J. Holmes

The assimilation of nitrogen by N-limited microalgae has profound effects on respiratory and photosynthetic metabolism. The addition of inorganic nitrogen causes a rapid increase in the rate of amino acid synthesis, which increases the requirements for keto-acids. This results in a large increase in the demand for tricarboxylic acid cycle intermediates. To meet this demand, tricarboxylic acid cycle activity increases, resulting in high rates of respiratory CO2 release during photosynthesis. Tricarboxylic acid cycle reductant, produced during ammonium assimilation, is oxidized via the mitochondrial electron-transport chain, resulting in a substantial increase in the rate of O2 consumption during photosynthesis. When [Formula: see text] is assimilated, tricarboxylic acid cycle activity increases, but there is little effect on mitochondrial O2 consumption. This implies that the tricarboxylic acid cycle reductant produced during [Formula: see text] assimilation is oxidized by some mechanism other than the mitochondrial electron-transport chain, possibly through the reduction of [Formula: see text].These results show that both the tricarboxylic acid cycle and the mitochondrial electron-transport chain are capable of operation during photosynthesis and that a major role of mitochondrial respiration during photosynthesis is the provision of carbon skeletons for biosynthetic reactions. The increase in tricarboxylic acid cycle activity during nitrogen assimilation is supported by anaplerotic reactions. The requirement for substrates by these reactions causes a redirection of recent photosynthate from the synthesis of starch to glycolysis and the tricarboxylic acid cycle. This corresponds with a decrease in the concentration of ribulose bisphosphate in the chloroplast. Under some conditions the concentration of ribulose bisphosphate drops below the ribulose bisphosphate binding site density of ribulose bisphosphate carboxylase:oxygenase resulting in ribulose bisphosphate limitation of photosynthetic carbon fixation. When ammonium is the added N source, there is a corresponding decrease in gross photosynthetic oxygen evolution. When [Formula: see text] is added, the decreased demand for photogenerated reductant brought about by a decrease in Calvin cycle activity is offset by an increase in electron flow to [Formula: see text].


1963 ◽  
Vol 42 (4) ◽  
pp. 480-484 ◽  
Author(s):  
B. Eckstein ◽  
R. Landsberg

ABSTRACT The succinic, malic and isocitric dehydrogenases in the ovary of immature and mature, normal and serum gonadotrophin injected rats were examined. The Qo2 of these enzymes were markedly enhanced in the gonadotrophin injected rats of both age groups, except in the case of succinic dehydrogenase in the ovary of the immature rats, where a slight non-significant decrease was noted. It is concluded that in the mature rat ovary, gonadotrophin administration stimulates the activity of all the examined dehydrogenases of the citric acid cycle, whereas in the immature rat ovary, at least the isocitric- and malic dehydrogenases are thus stimulated.


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