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Micronutrients
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
Adenosine Triphosphate is an example of an essential non-vitamin coenzyme. In fact, Adenosine Triphosphate or Adenosine-5´-Triphosphate (ATP) is a nucleoside triphosphate composed of three compounds: a nitrogenous heterocyclic base (adenine), the sugar β-D-ribose, and three phosphate groups (92–93, 97–98). ATP is considered the single most important molecule in the cell and is often referred to as a molecule of intracellular energy transfer and as a universal coenzyme (type co-substrate) for a large number of enzymes, especially kinases (92, 98). In general, ATP carries both phosphate and energy to different places within a cell for the release of energy in situ by losing one or two of its phosphate groups, becoming adenosine diphosphate (ADP) or adenosine monophosphate (AMP), respectively. Much of the chemical energy used by cells is stored in the two phosphor-anhydride bonds of ATP which are high in energy (92, 97–98).
Pharmacological Modification of a Cerebroplegia Solution
Published in Richard A. Jonas, Jane W. Newburger, Joseph J. Volpe, John W. Kirklin, Brain Injury and Pediatric Cardiac Surgery, 2019
Richard A. Jonas, Aoki Mitsuru
Magnetic Resonance Spectroscopy. 31P magnetic resonance spectra were acquired in the Fourier transform mode on a custom-built spectrometer using the Oxford horizontal-bore 4.7 Tesla magnet and surface coil. The field homogeneity was optimized with the brain water signal. Spectra were acquired using a 90-degree excitation pulse of 60 microseconds. Each spectrum was the average of 128 acquisitions (nine minutes). Peak areas of inorganic phosphate (Pi), creatine phosphate (PCr), and beta nucleoside triphosphate were determined by Lorentzian curve fitting and peak integration (NMRI Software, New Methods Research, East Syracuse, NY). Changes in ATP concentration were assessed from the beta nucleoside triphosphate peak area. The inorganic phosphate, creatine phosphate, and ATP data are reported as percentage of the baseline data obtained during the last nine minutes of the initial full-flow normothermic bypass period. The intracellular pH in the brain (pHi) was calculated from the chemical shift of the inorganic phosphate peak relative to the creatine phosphate peak.
The Primer Hypothesis for the Regulation of Eukaryotic Gene Expression
Published in M. Gerald, M.D. Kolodny, Eukaryotic Gene Regulation, 2018
To test whether oligonucleotides can be incorporated en bloc during RNA synthesis, radioactively labeled oligonucleotides were added to systems which were transcribing RNA and the newly transcribed RNA examined for radioactive label. Such systems included whole cells and isolated nuclei. Nuclear transcription systems were considered to have two principal advantages over whole cells. Cell membranes would be expected to have permeability barriers to exogenously supplied macromolecules. Besides this problem of transport into the cell, there is an additional problem in whole cells of utilization of labeled mononucleotide breakdown products of the added oligonucleotides. Nuclear transcription systems have been described as requiring nucleoside triphosphates for RNA synthesis. Therefore, any label seen in newly synthesized RNA would have to originate in oligonucleotides rather than mononucleotide breakdown products.
Effect of adenosine triphosphate on amiodarone-induced optic neuropathy in rats: biochemical and histopathological evaluation
Published in Cutaneous and Ocular Toxicology, 2023
Kemal Bayrakçeken, Rukiye Kilic Ucgul, Taha Coban, Gulce Yazıcı, Halis Suleyman
Although the pathogenesis of amiodarone-related toxic effects has not been fully elucidated, Betiu et al. suggested that amiodarone induced adenosine triphosphate (ATP) depletion in cells [10]. ATP is a nucleoside triphosphate consisting of adenine, ribose, and three phosphate groups [11]. In the literature, it has been reported that ATP is involved in the synthesis of antioxidants scavenging and clearing ROS [12]. Moreover, it is known that ATP is an energy source for the synthesis of low-molecular-weight antioxidants [13]. Given these outcomes, amiodarone-induced optic neuropathy may be secondary to increased ROS production and ATP deficiency. However, to the best of our knowledge, the literature contains no study investigating the effect of ATP on amiodarone-induced optic neuropathy. Therefore, the current study aims to evaluate the effect of ATP on possible optic nerve damage caused by amiodarone in rats, and to examine the optic nerve tissue biochemically and histopathologically.
Advances in biocatalytic and chemoenzymatic synthesis of nucleoside analogues
Published in Expert Opinion on Drug Discovery, 2022
Sebastian C. Cosgrove, Gavin J. Miller
However, many challenges remain. First and foremost, is the issue of scalability. Whilst specific examples of successfully developing scalable enzymatic cascade syntheses exist (vide supra), a wider development to transfer analytical to preparative capability is vital; technology developments, for example continuous flow processes, may help to surmount this challenge. When designing a biocatalytic process, there is a double-faceted optimization that is required: optimizing the enzyme, and the reaction it catalyzes. This often presents itself as an issue with regard to scaling a reaction; the time it takes to optimize enzyme production can leave little to do with the reaction itself. Approaches that improve expression levels and enzyme stability therefore play important roles in bioprocess optimization; here the use of immobilization may play a key role. Scaffold diversification is also a critical consideration. The evolution of broadly promiscuous nucleoside processing enzymes will enable rapid access to explore diverse pharmacophore space, from the perspectives of both the sugar ring and hetereobase components. Chemical synthesis will synergize here for some time as it remains the current tool to efficiently effect atom-specific structural modifications of key building blocks for further synthesis. Finally, contemplation of the requirements to utilize nucleosides and their analogues in nucleic acid chemistry requires that access to appropriate kinase (or similar) phosphorylation systems are robust (and potentially scalable), to provide the necessary nucleotide triphosphates.
Hepatic manifestations of COVID-19 and effect of remdesivir on liver function in patients with COVID-19 illness
Published in Baylor University Medical Center Proceedings, 2021
Abdul Aleem, Guruprasad Mahadevaiah, Nasir Shariff, Jiten P. Kothadia
Remdesivir (GS-5734) is a pro-drug of a monophosphate nucleoside analog (GS-441524) and manifests as a viral RNA-dependent RNA polymerase (RdRp) inhibitor that targets the viral genome replication process. Hypothetically, nucleoside analogs are unable to permeate the cell wall easily. Upon gaining entry into the host cell, the adenosine nucleotide pro-drug is metabolized to a nucleoside monophosphate intermediate by carboxyesterase 1 and/or cathepsin A. The nucleoside monophosphate undergoes subsequent phosphorylation to produce nucleoside triphosphate, which resembles adenosine triphosphate and can be used by the RdRp enzymes or complexes for genome replication. After remdesivir is metabolized into the pharmacologic active analog adenosine triphosphate (GS-443902) by the host cells, it vies with adenosine triphosphate for integration by the RdRp complex into the nascent RNA strand and, upon subsequent integration of a few more nucleotides, results in termination of viral RNA synthesis.17–21