scholarly journals Energy Metabolism in the Placenta and the Role of Disturbances in the Development of Placental Insufficiency at an Exacerbation of Cytomegalovirus Infection

2016 ◽  
Vol 71 (3) ◽  
Author(s):  
M. T. Lucenko ◽  
I. A. Andrievskaya ◽  
I. V. Dovzhikova
Keyword(s):  
Energy Metabolism ◽  
Lipoic Acid ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Morphological Structure ◽  
Placental Insufficiency ◽  
City Hospital ◽  
Cmv Infection ◽  
Scientific Center ◽  
Ketoglutarate Dehydrogenase

Objective. Determine the characteristics of placental energy metabolism and to establish its role in the development of placental insufficiency at an exacerbation of cytomegalovirus (CMV) infection in 25–28 weeks of gestation.Methods. In a prospective study of the case-control type included pregnant, delivery on term of 37–38 weeks. The sample of 50 pregnant women, including 25 CMV-seropositive with exacerbation of CMV infection at 25–28 weeks of gestation and with the titer of IgG antibodies to CMV 1: 1600 at the time of the study and 25 CMV-seronegative women the same pregnancy. The study was conducted at the obstetric department of pathology of pregnancy and laboratory «Etiopathogenesis mechanisms and recovery processes with non-specific lung diseases» Far Eastern Scientific Center of Physiology and Pathology of Respiration together with the urban maternity ward at City Hospital in the period from 2014 to 2015. The activity of pyruvate dehydrogenase, α-ketoglutarate dehydrogenase and a dehydrogenase lipoic acid was determined by histochemical methods on cryostat sections of fresh frozen tissue placenta by the method of R. Lilly. Evaluation of the intensity of histochemical reactions carried out by the program cytophotometry Scion. The morphology of the placenta was studied in paraffin sections stained with hematoxylin Böhmer-eosin, van Gieson’s picrofuchsin and alcian blue by Steedman. Results. Exacerbation of CMV infection at 25–28 weeks of gestation leads to a decrease in the intensity of the histochemical reaction of pyruvate dehydrogenase in 2.4 times, lipoic acid dehydrogenase — in 2.9 times, and α-ketoglutarate dehydrogenase — in 1.5 times in the syncytiotrophoblast villous placenta. The placental morphological structure study showed villi in a state of death or necrotic changes, as well as increasing the number of avascular immature villi. In the maternal part of the placenta were marked constriction clearances, hypertrophy of muscle and connective tissue layers blood vessels. The conclusion. The findings suggest that the exacerbation of CMV infection at 25–28 weeks of pregnancy causes a decrease in the intensity of energy metabolism in the placenta by suppressing the activity of the enzymes α-ketoglutarate dehydrogenase and pyruvate dehydrogenase complex, which is accompanied by disturbances of the morphological structure of the placental barrier, the development of placental insufficiency. 

Interaction of α-Lipoic acid enantiomers and homologues with the enzyme components of the mammalian pyruvate dehydrogenase complex

1995 ◽  
Vol 50 (5) ◽  
pp. 637-646 ◽  
Author(s):  
Sabine Löffelhardt ◽  
Christoph Bonaventura ◽  
Mathias Locher ◽  
Harald O. Borbe ◽  
Hans Bisswanger
Keyword(s):  
Lipoic Acid ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Dehydrogenase Complex

scholarly journals Targeting Altered Energy Metabolism in Colorectal Cancer: Oncogenic Reprogramming, the Central Role of the TCA Cycle and Therapeutic Opportunities

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1731 ◽  
Author(s):  
Carina Neitzel ◽  
Philipp Demuth ◽  
Simon Wittmann ◽  
Jörg Fahrer
Keyword(s):  
Colorectal Cancer ◽  
Energy Metabolism ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Tca Cycle ◽  
Dietary Factors ◽  
Pyruvate Dehydrogenase Kinase ◽  
Driver Mutations ◽  
The Tca Cycle

Colorectal cancer (CRC) is among the most frequent cancer entities worldwide. Multiple factors are causally associated with CRC development, such as genetic and epigenetic alterations, inflammatory bowel disease, lifestyle and dietary factors. During malignant transformation, the cellular energy metabolism is reprogrammed in order to promote cancer cell growth and proliferation. In this review, we first describe the main alterations of the energy metabolism found in CRC, revealing the critical impact of oncogenic signaling and driver mutations in key metabolic enzymes. Then, the central role of mitochondria and the tricarboxylic acid (TCA) cycle in this process is highlighted, also considering the metabolic crosstalk between tumor and stromal cells in the tumor microenvironment. The identified cancer-specific metabolic transformations provided new therapeutic targets for the development of small molecule inhibitors. Promising agents are in clinical trials and are directed against enzymes of the TCA cycle, including isocitrate dehydrogenase, pyruvate dehydrogenase kinase, pyruvate dehydrogenase complex (PDC) and α-ketoglutarate dehydrogenase (KGDH). Finally, we focus on the α-lipoic acid derivative CPI-613, an inhibitor of both PDC and KGDH, and delineate its anti-tumor effects for targeted therapy.

scholarly journals The Pyruvate Dehydrogenase Complex in Sepsis: Metabolic Regulation and Targeted Therapy

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhenhua Zeng ◽  
Qiaobing Huang ◽  
Liangfeng Mao ◽  
Jie Wu ◽  
Sheng An ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Pyruvate Dehydrogenase ◽  
Metabolic Regulation ◽  
Pyruvate Dehydrogenase Complex ◽  
Aerobic Oxidation ◽  
Tca Cycle ◽  
Protective Effects ◽  
Multienzyme Complex ◽  
Therapeutic Drugs ◽  
Dehydrogenase Complex

Anaerobic glycolysis is the process by which glucose is broken down into pyruvate and lactate and is the primary metabolic pathway in sepsis. The pyruvate dehydrogenase complex (PDHC) is a multienzyme complex that serves as a critical hub in energy metabolism. Under aerobic conditions, pyruvate translocates to mitochondria, where it is oxidized into acetyl-CoA through the activation of PDHC, thereby accelerating aerobic oxidation. Both phosphorylation and acetylation affect PDHC activity and, consequently, the regulation of energy metabolism. The mechanisms underlying the protective effects of PDHC in sepsis involve the regulation on the balance of lactate, the release of inflammatory mediators, the remodeling of tricarboxylic acid (TCA) cycle, as well as on the improvement of lipid and energy metabolism. Therapeutic drugs that target PDHC activation for sepsis treatment include dichloroacetate, thiamine, amrinone, TNF-binding protein, and ciprofloxacin. In this review, we summarize the recent findings regarding the metabolic regulation of PDHC in sepsis and the therapies targeting PDHC for the treatment of this condition.

scholarly journals Kinetic analysis of the role of lipoic acid residues in the pyruvate dehydrogenase multienzyme complex of Escherichia coli

1980 ◽  
Vol 187 (2) ◽  
pp. 393-401 ◽  
Author(s):  
Mary C. Ambrose-Griffin ◽  
Michael J. Danson ◽  
William G. Griffin ◽  
Geoffrey Hale ◽  
Richard N. Perham
Keyword(s):  
Escherichia Coli ◽  
Lipoic Acid ◽  
Pyruvate Dehydrogenase ◽  
Active Sites ◽  
Catalytic Mechanism ◽  
Pyruvate Dehydrogenase Complex ◽  
Enzymic Activity ◽  
Complex Activity ◽  
Kinetics Of

The catalytic roles of the two reductively acetylatable lipoic acid residues on each lipoate acetyltransferase chain of the pyruvate dehydrogenase complex of Escherichia coli were investigated. Both lipoyl groups are reductively acetylated from pyruvate at the same apparent rate and both can transfer their acetyl groups to CoASH, part-reactions of the overall complex reaction. The complex was treated with N-ethylmaleimide in the presence of pyruvate and the absence of CoASH, conditions that lead to the modification and inactivation of the S-acetyldihydrolipoic acid residues. Modification was found to proceed appreciably faster than the accompanying loss of enzymic activity. The kinetics of the modification were fitted best by supposing that the two lipoyl groups react with the maleimide at different rates, one being modified at approximately 3.5 times the rate of the other. The loss of complex activity took place at a rate approximately equal to that calculated for the modification of the more slowly reacting lipoic acid residue. The simplest interpretation of this result is that only this residue is essential in the overall catalytic mechanism, but an alternative explanation in which one lipoic acid residue can take over the function of another was not ruled out. The kinetics of inactivation could not be reconciled with an obligatory serial interaction between the two lipoic acid residues. Similar experiments with the fluorescent N-[p-(benzimidazol-2-yl)phenyl]maleimide supported these conclusions, although the modification was found to be less specific than with N-ethylmaleimide. The more rapidly modified lipoic acid residue may be involved in the system of intramolecular transacetylation reactions that couple active sites in the lipoate acetyltransferase component.

scholarly journals Polypeptide-chain stoicheiometry and lipoic acid content of the pyruvate dehydrogenase complex of Escherichia coli

1979 ◽  
Vol 177 (1) ◽  
pp. 129-136 ◽  
Author(s):  
G Hale ◽  
R N Perham
Keyword(s):  
Escherichia Coli ◽  
Lipoic Acid ◽  
Pyruvate Dehydrogenase ◽  
Acid Content ◽  
Polypeptide Chain ◽  
Pyruvate Dehydrogenase Complex ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Pyruvate Decarboxylase ◽  
Molar Ratios

The pyruvate dehydrogenase multienzyme complex was isolated from Escherichia coli grown in the presence of [35S]sulphate. The three component enzymes were separated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and the molar ratios of the three polypeptide chains were determined by measurement of the radioactivity in each band. The chain ratio of lipoamide dehydrogenase to lipoate acetyltransferase approached unity, but there was a molar excess of chains of the pyruvate decarboxylase component. The 35S-labelled complex was also used in a new determination of the total lipoic acid content. It was found that each polypeptide chain of the lipoate acetyltransferase component appears to bear at least three lipoyl groups.

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