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The Scientific Basis of Medicine
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Chris O'Callaghan, Rachel Allen
Genetic information is stored and transferred in the form of the nucleic acids deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). These molecules provide the necessary information for protein production. Like many biological molecules, nucleic acids are multimers of smaller units; which in this case are known as nucleotides. A set of four nucleotide components is used to generate DNA or RNA. Adenine (A), guanine (G) and cytosine (C) are common to both DNA and RNA. Thymine (T) is found in DNA but absent from RNA, with uracil (U) present in its place.
Micronutrients
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
Guanosine-5’-Triphosphate is a nucleotide containing the heterocyclic base Guanine. Like ATP, GTP carries energy in phospho-anhydride bonds. In terms of co-substrate/coenzyme activity, GTP is the ‘energy source’ for the reactions of protein synthesis. GTP also serves an important role in the cellular response to signal molecules, for instance, hormones (92).
Role of Natural Agents in the Management of Diabetes
Published in Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg, Promising Drug Molecules of Natural Origin, 2020
Monika Elżbieta Jach, Anna Serefko
Galega officinalis is a leguminous plant, which aerial parts have long been used in traditional and folk medicine to treat diabetes in Chile, Japan as well as Europe (Bailey and Day, 2004; Gunn and Farnsworth, 2013; Rios et al., 2015). This herb consists of two nitrogen guanidine constituents: galegin (syn. galegine) as isoamylene guanidine and hydroxygalegine prevalent in all parts during flowering and forming fruits. These bioactive substances possess pharmacological features as hypoglycemic and galactogenic factors. However, guanidine is excessively toxic for clinical treat; hence, the study focused on galegine, which turned out to be less toxic as an extract of G. officinalis. In the 1920s, the extract was specified as an antidiabetic formulation (Bailey and Day, 2004; Martínez-Larrañaga and Martínez, 2018).
Response to “Hydroxyl radical is predominantly involved in oxidatively generated base damage to cellular DNA exposed to ionizing radiation” by Cadet et al.
Published in International Journal of Radiation Biology, 2023
Cynthia Burrows, Aaron Fleming
We recently reviewed the aspects of guanine oxidation chemistry in which we compared and contrasted oxidation by ionizing radiation vs. endogenous oxidative stress (Fleming and Burrows 2022). Cadet et al. (2022) and Halliwell et al. (2021) repeatedly mis-state our work as involving “conversion of highly reactive •OH into mildly oxidizing carbonate anion radical.” The reaction of •OH with bicarbonate is slow, and it has never been proposed to be relevant in our work with endogenous oxidative stress. Rather, the Fenton reaction of Fe(II) complexes, with or without bound phosphate, with hydrogen peroxide in the presence of bicarbonate proceeds by an inner-sphere mechanism (Cotton and Wilkinson 1972), consistent with the results of Meyerstein et al. (Illes et al. 2019). In such a reaction, hydroperoxide and carbonate are both bound to Fe(II) and react at pH 7 to produce carbonate radical anion directly, without any intermediate formation of •OH. In accord with this mechanism, we demonstrated that the presence of bicarbonate in the Fenton reaction leads to a different set of guanine oxidation products than that seen from classical radiation (hydroxyl radical) chemistry (Fleming and Burrows 2020).
Antibody-drug conjugates (ADCs) delivering pyrrolobenzodiazepine (PBD) dimers for cancer therapy
Published in Expert Opinion on Biological Therapy, 2021
Anthramycin was the first of the pyrrolobenzodiazepine (PBD) family of antitumour antibiotics to be discovered in the 1960s. This class of naturally occurring, and later synthetic, compounds are tricyclic systems consisting of an aromatic A-ring, a 1-4-diazepin-5-one B-ring and a pyrrolidine C-ring (Figure 1(a)). Their mechanism of action involves sequence selective binding in the minor groove of DNA and covalent binding to the exocyclic C2-amino group of guanine bases. Wholly synthetic PBD dimers, in which two PBD monomer units are joined through their C8-positions via a flexible tether, are significantly more cytotoxic due to their ability to form two covalent bonds and thereby cross-link DNA. The development of PBDs and PBD dimers as stand-alone agents has been reviewed previously [1,2].
Molecular and epigenetic modes of Fumonisin B1 mediated toxicity and carcinogenesis and detoxification strategies
Published in Critical Reviews in Toxicology, 2021
Thilona Arumugam, Terisha Ghazi, Anil A. Chuturgoon
The threat of oxidative damage is particularly significant to nucleic acids. Elevated levels of ROS can induce strand breaks, protein-DNA crosslinking and has mutagenic potential (Loft et al. 2008). Several studies have demonstrated the genotoxic potential of FB1 in humans and animals. With the use of the micronuclei test, Ehrlich et al. (2002), Theumer et al. (2010), and Karuna and Rao (2013) assessed genotoxic potential of FB1. Micronuclei are formed when there are breakages in chromosomes or when spindle assembly is disturbed. A dose-dependent formation of micronuclei occurred in FB1-exposed HepG2 cells (Ehrlich et al. 2002) and Wistar rats (Theumer et al. 2010). Conversely, FB1 failed to induce micronuclei in BALB/C mice (Karuna and Rao 2013). DNA strand breaks and fragmentation were studied in vivo and in vitro. These studies found that DNA fragmentation and strand breaks occurred as a consequence of FB1-induced oxidative stress (Atroshi et al. 1999; Mobio et al. 2003; Stockmann-Juvala et al. 2004b; Theumer et al. 2010; Hassan et al. 2015). 8-Hydroxy-deoxyguanosine (8-OHdG) is a predominant oxidative DNA lesion, and thus widely used as a critical biomarker for oxidative stress and carcinogenesis (Valavanidis et al. 2009). FB1 mediated the oxidation of guanine in both in vivo and in vitro studies (Mobio et al. 2003; Mary et al. 2012). Only one study found that DNA damage occurred independent of ROS levels (Galvano et al. 2002).