Modifications of Cellular Radiation Damage
Kedar N. Prasad in Handbook of RADIOBIOLOGY, 2020
This is a four-carbon fatty acid that occurs naturally in the body and is formed by the hydrolysis of ethyl butyrate. High fiber diet can generate a millimolar level of butyric acid in the colon. Recent studies show that this fatty acid affects morphology, growth rate, and gene expression in several mammalian tumor cells in culture.122,123 Sodium butyrate enhances the growth inhibitory effect of X-irradiation on mouse neuroblastoma cells in culture (Figure 5.6). Because sodium butyrate inhibits anaerobic glycolysis by reducing lactic acid dehydrogenase activity,124 and because neuroblastoma cells are more sensitive to inhibitors of anaerobic glycolysis than other cell types,125 sodium butyrate-induced cell death and enhancement of radiation response may, in part, be related to inhibition of anaerobic glycolysis. The fact that dl-glyceraldehyde, an inhibitor of anaerobic glycolysis, also inhibits growth and increases the radiation response of neuroblastoma cells in culture (Figure 5.4), supports the above view.
The Modification of Lysine
Roger L. Lundblad in Chemical Reagents for Protein Modification, 2020
The reaction of glyceraldehyde with carbonmonoxyhemoglobin S has been explored by Acharya and Manning.113 This reaction was performed with 0.010 M glyceraldehyde in phosphate-buffered saline, pH 7.4, and the resultant Schiff bases were stabilized by reduction with sodium borohydride. Using radiolabeled glyceraldehyde, these investigators were able to obtain support for the concept that there is selectivity in the reaction of sugar aldehydes with hemoglobin. The reaction product between glyceraldehyde and hemoglobin S did have stability properties without reduction that were not consistent with only Schiff base products. These investigators suggested that the glyceraldehyde-hemoglobin Schiff base could undergo an Amadori rearrangement (Figure 43) to form a stable ketoamine adduct which could be reduced with sodium borohydride to form a product identical to that obtained by direct reduction of the Schiff base. In a subsequent study, these investigators did show that the glyceraldehyde-hemoglobin S Schiff base could rearrange to form a ketamine via an Amadori rearrangement.114 These investigators were able to use reaction with phenylhydrazine to detect the protein-bound ketamine adduct as shown in Figure 44.
Vitamin C and Cancer
Qi Chen, Margreet C.M. Vissers in Cancer and Vitamin C, 2020
While pharmacologic ascorbate appears to have cytotoxic effects on many cancer cells through hydrogen-peroxide-mediated pro-oxidant damage, in a subset of cancer cells, additional related mechanisms have been described. Cytotoxicity may be due to oxidation of ascorbate into an unstable metabolite and reversible oxidized form of ascorbate, dehydroascorbic acid [70]. Tumor cells internally reduce dehydroascorbic acid to ascorbate-triggering glutathione scavenging, inducing oxidative stress, inactivating glyceraldehyde 3-phosphate dehydrogenase, inhibiting glycolytic flux, and ultimately leading to an energy crisis leading to cell death [71,72]. For example, cultured human colorectal cancer cells with KRAS or BRAF mutations were selectively killed by pharmacologic ascorbate by depletion of intracellular glutathione. This is followed by inactivation of glyceraldehyde 3-phosphate dehydrogenase, leading to inhibition of glycolysis and death in cancer cells highly dependent on glycolysis [71]. Pharmacologic ascorbate can also induce metabolic stress by depletion of NAD in several cancer cell lines [73,74].
Toxicological assessment of electronic cigarette vaping: an emerging threat to force health, readiness and resilience in the U.S. Army
Published in Drug and Chemical Toxicology, 2022
Marc A. Williams, Gunda Reddy, Michael J. Quinn, Amy Millikan Bell
Additionally, acrolein oxidation by lung or liver microsomes forms the metabolite glycidaldehyde, which could promote skin tumors in mice on dermal contact (DHHS ATSDR 2007). Glycidaldehyde can be further metabolized to glyceraldehyde, which then enters the glycolytic pathways. In a proposed model (Patel et al.1980), glycidaldehyde appears to be the only chemical that could represent a risk to human health, since it exhibited carcinogenic properties in mice and rats when applied dermally (Van Duuren et al.1967a, 1967b, Shamberger et al.1974). Although this metabolic system has been demonstrated in animal models, it has not been shown in human biological systems on inhalation exposure. However, one particular study (Lam et al.1985), found a dose-related depletion of glutathione in the nasal respiratory mucosa in a rat model following inhalational exposure to 0.1–2.5 ppm of acrolein for three hours. This observation was interpreted as being consistent with a chemical reaction that yielded glutathione-acrolein adducts (Lam et al.1985).
Neuroprotective effects of oleuropein on retina photoreceptors cells primary culture and olive leaf extract and oleuropein inhibitory effects on aldose reductase in a diabetic model: Meriones shawi
Published in Archives of Physiology and Biochemistry, 2022
Maha Benlarbi, Hedya Jemai, Khouloud Hajri, Sihem Mbarek, Emna Amri, Mariem Jebbari, Imane Hammoun, Basma Baccouche, Nourhène Boudhrioua Mihoubi, Ayachi Zemmal, Rafika Ben Chaouacha-Chekir, Wissal Dhifi
In fact, AR which is a NADPH-dependent enzyme converts 3% glucose into sorbitol under normal physiological conditions. Its activity becomes important when the blood glucose level increases. In vitro, it converts glyceraldehyde to glycerol with an equimolar oxidation of NADPH. Our results were consistent with those of Travis et al. (1971), who reported that an activation of the polyol pathway was noticed when intracellular glucose levels increase. Indeed, the incubation of erythrocytes with 50 mM glucose increased the contents of two main metabolites generated by this pathway: sorbitol and fructose. In addition, our results were also in agreement with those of Reddy et al. (2008) according to them, AR in erythrocyte fraction was significantly elevated in patients with DR not only compared to non-diabetic animals but also to diabetic ones without developing DR. Moreover, the same authors reported an AR activity at early disease stages and not only in its advanced ones.
Effects of the Cobalt-60 gamma radiation on Pichia pastoris glyceraldehyde-3-phosphate dehydrogenase
Published in International Journal of Radiation Biology, 2022
Abdelghani Iddar, Mohammed El Mzibri, Adnane Moutaouakkil
Due to the abundance of proteins in the cell, their reactivity with the products of water radiolysis is higher. The free radicals formed react with proteins, nucleic acids and lipids, which leads to their damage. Understanding the action of free radicals on proteins should provide a better understanding of the biological processes for cells adaptation to radiation (Headlam and Davies 2003; Kowalczyk et al. 2008). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key enzyme of the glycolytic pathway, found at high concentrations and with multitude of functions in the eukaryotic organisms (Punt et al. 1990). GAPDH has been studied virtually in all organisms and all glycolytic GAPDHs are homotetrameric, which have been remarkably conserved during evolution (Cerff 1995). The enzyme catalyzes the reversible phosphorylation and oxidation of glyceraldehyde-3-phosphate to generate 1,3-diphosphoglycerate, which is used by phosphoglycerate kinase to produce the adenosine triphosphate (ATP) (Forthergill-Gilmore and Michels 1993). In addition, GAPDH has been shown to play vital other roles in eukaryotic metabolism related to the cell cycle, cancer, apoptosis, proteins regulation, gene transcription, DNA replication, DNA repair, and nuclear ribonucleic acid (nRNA) export (Morgenegg et al. 1986; Meyer-Siegler et al. 1991; Singh and Green 1993; Zheng et al. 2003; Tarze et al. 2007; Kornberg et al. 2010; Das et al. 2016). On the other hand, it has been indicated that GAPDH expression is modified by various cell stress and it is involved in regulation of ROS in cells (Hara et al. 2005; Fourrat et al. 2007; Henry et al. 2015).
Related Knowledge Centers
- Aldose
- Glycerol
- Monosaccharide
- Oxygen
- Sweetness
- Metabolism
- Carbohydrate
- Chemical Formula
- Carbon
- Hydrogen