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Fuel Metabolism in the Fetus
Published in Emilio Herrera, Robert H. Knopp, Perinatal Biochemistry, 2020
As a general rule, except in Brown Adipose Tissue, coupling between substrate oxidation and ADP phosphorylation in the mitochondria is due to an electrochemical gradient of protons, on either side of the mitochondrial membrane. During the transfer of electrons to oxygen, protons are extruded from the mitochondrial matrix. These protons cannot be readily reintroduced into the matrix, except in the part of the membrane where ATP-synthase is located. This results in ATP production (Figure 3a left side). Thus electron transfer from substrates to oxygen leads to stochiometric amounts of ATP (coupled oxidative phosphorylation). By contrast, in brown adipocyte mitochondria, the permeability of the inner membrane to protons is abnormally high and protons can readily cross the mitochondrial membrane. The free energy of substrates will therefore be released without ATP synthesis (uncoupled oxidative phosphorylation) and this will result in heat production22 (Figure 3a right side). The high permeability of the inner membrane to protons is related to a specific protein called the uncoupling protein or thermogenin. Interestingly, recent data indicate that thermogenin is present in late gestation in brown adipose tissue of fetuses from many species.25,26
Ethylmalonic encephalopathy
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Since the initial report, only about 40 cases of ethylmalonic encephalopathy have been described worldwide, suggesting that this condition is an ultra-rare autosomal recessive disorder. Most patients with ethylmalonic encephalopathy have been, with a few exceptions, of Mediterranean [5, 6, 8, 14] or Arabic [7] descent. However, the actual incidence of this condition could have been significantly underestimated because the biochemical phenotype may be incorrectly attributed to other metabolic disorders, particularly defects of the mitochondrial electron-transfer pathway. Several patients of ethylmalonic encephalopathy were initially diagnosed as glutaric aciduria type II, but this diagnosis was not confirmed by in vitro enzyme assays or molecular studies. Some of these patients were proven and more could have been ethylmalonic encephalopathy.
Role of Ascorbate and Dehydroascorbic Acid in Metabolic Integration of the Cell
Published in Qi Chen, Margreet C.M. Vissers, Vitamin C, 2020
Gábor Bánhegyi, András Szarka, József Mandl
A special case of the over-reduction of the electron transfer chain occurs when one or more complex(es) does/do not work properly due to mutation(s) in its/their gene(s). Because of the earlier arguments, the consequences of the impairment of electron transfer chain elements might be mitigated by ascorbate therapy. The enhanced generation of superoxide—observed in fibroblasts from patients with electron transport chain deficiencies—could be decreased by ascorbate treatment [72]. The activities of I–III and II–III complexes could simultaneously be stimulated by vitamin C supplementation of the cell culture media [72]. There were attempts to use the ascorbate-DHA redox couple and vitamin K as a therapeutic agent in the therapy of mitochondrial diseases. A young woman with mitochondrial myopathy and severe exercise intolerance was treated by vitamin C and menadione to bypass the block in complex III [43,44], because the redox potentials of these electron carriers fit the gap created by the cytochrome c dysfunction [27]. Unfortunately, after an initial improvement documented by 31P nuclear magnetic resonance spectroscopy of muscle [2], this state was not sustained. (Menadione had to be discontinued because of its withdrawal by the U.S. Food and Drug Administration [43].) Except for this case, effective vitamin C therapy in other patients suffering from mitochondrial diseases has not been reported.
Silver nanoparticles suppress forskolin-induced syncytialization in BeWo cells
Published in Nanotoxicology, 2022
Yuji Sakahashi, Kazuma Higashisaka, Ryo Isaka, Rina Izutani, Jiwon Seo, Atsushi Furuta, Akemi Yamaki-Ushijima, Hirofumi Tsujino, Yuya Haga, Akitoshi Nakashima, Yasuo Tsutsumi
Progression of syncytialization is regulated by various pathways centered on the cyclic adenosine monophosphate signal (Wang et al. 2014). In mice, oxidative phosphorylation in mitochondria is enhanced, and ATP production is increased, during early placental formation (Miyazawa et al. 2017). In this regard, silver nanoparticles are hazardous to multiple organelles such as mitochondria (Gurunathan et al. 2019), which play important roles in ATP production. As a mechanism by which nAg10 inhibits forskolin-induced syncytialization, we hypothesize that nAg10 taken up by BeWo cells are distributed in the mitochondria and cause them to malfunction in such processes as ATP synthesis. From this viewpoint, we performed an inductively coupled plasma mass spectrometry (ICP-MS) analysis to evaluate the cellular uptake in the forskolin-plus-nAg10 (0.156 μg/mL)-treated cells. ICP-MS analysis showed that nAg10 was uptaken in BeWo cells and that localized in the nucleus and mitochondria (Supplementary Figure S1). We, therefore, need to evaluate their effect on mitochondrial dysfunction by examining mitochondrial electron transfer system activity and ATP production in nanoparticle-treated cells.
Electrochemical immunoassay for tumor markers based on hydrogels
Published in Expert Review of Molecular Diagnostics, 2018
In electrochemical immunoassays, redox species are usually employed to realize direct electron transfer at the immunosensing interfaces [59]. Adding redox species to the electrolyte solution is the simplest method, in which high concentrations of potassium ferricyanide are commonly introduced as the redox species into detection solution to arouse a detrimental impact on the activity of antibodies [60,61]. Modifying redox species directly on the substrate usually involves some membrane materials, such as nafion [62] and silicate films [63,64], to prevent the redox species from leaking. However, such membranes may hinder the electron transfer due to their poor conductivity. Electroactive nanocomposites, which integrate redox species and conductive nanomaterials, have attracted much research attention and have been widely used in electrochemical immunoassay for tumor markers [29,50,65]. Nevertheless, these electroactive nanocomposites suffer from the problems of complicated manipulation, time-consuming synthesis procedures and potential instability. Preparing redox hydrogels via incorporating redox species is an effective way to overcome these problems and open a new avenue for designing novel redox composites [66] where the abundant specific functional groups of hydrogels can be used to enrich numerous redox species. In addition, the crosslinked hydrogel network can realize three-dimensional and homogeneous distribution of redox species, as well as rapid electron transfer. Incorporating redox moieties within a hydrogel matrix usually involves three approaches: complexing reaction, covalent crosslinking, and copolymerization.
Alcohol quantification: recent insights into amperometric enzyme biosensors
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Vinita Hooda, Vikas Kumar, Anjum Gahlaut, Vikas Hooda
Different approaches have been developed regarding the construction of amperometric enzyme electrodes to facilitate the direct electron transfer process in alcohol detection and improving the performance and operational stability of the biosensors. The execution of amperometric biosensor is based on the measurement of current which is related to the transfer of electrons from the active site of the immobilized enzyme to the surface of the working electrode. Generally this electron transfer reaction at the time of catalysis of biological molecules is very slow at ordinary electrodes surface. The challenging aspect of these electrochemical biosensors is to alleviate the rate of electron transfer between the enzyme and the electrode surface. Great attention has been focused for solving this problem by some methods which include the use of mediator-modified enzymes, electrodes modified by membrane for electron transfer, by conducting or non-conducting-polymer matrices, by sol–gel-based supports, by hydrogel supports, by screen printed support or use of nanoparticles as electrode materials. Some of these strategies are reviewed and their applications to alcohol biosensors are described.