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Vitamin C and Cancer
Published in Qi Chen, Margreet C.M. Vissers, Cancer and Vitamin C, 2020
Channing Paller, Tami Tamashiro, Thomas Luechtefeld, Amy Gravell, Mark Levine
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].
Biochemical Methods of Studying Hepatotoxicity
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
Prasada Rao S. Kodavanti, Harihara M. Mehendale
lodoacetate, pH 7.4 (2 mM): Dissolve 42 mg of sodium iodoacetate in distilled water, adjust pH to 7.4 with NaOH, and make volume up to 100 ml. Iodoacetate prevents the catalysis of glyceraldehyde-3-phosphate.
Biocatalysts: The Different Classes and Applications for Synthesis of APIs
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
The aldolase-catalyzed reaction proceeds via two different mechanisms, a Schiff base formation (class I aldolases) or by Zn2+ activation (class II aldolases), as depicted in the opposite scheme for DHAP-dependent enzymes. The mechanism of class I aldolases (a) is characterized by the formation of an imine between the terminal amino group of a Lys residue and the carbonyl oxygen atom of the substrate DAHP. The imine may rearrange to an enamine that attacks nucleophilicly the aldehyde carbonyl carbon. Subsequent hydrolysis gives the new aldol and the free enzyme. The first steps in the reaction mechanism of the class II aldolases such as tagatose-1,6-diphosphate aldolase or fructose-1,6-diphosphate aldolase (b) are the binding of DAHP and the abstraction of a proton from the activated C1 by a functional group of the active site. The following steps (not shown), are glyceraldehyde-3-phosphate binding with subsequent C–C bond formation, and proton transfer.
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).
Fructose and hepatic insulin resistance
Published in Critical Reviews in Clinical Laboratory Sciences, 2020
Samir Softic, Kimber L. Stanhope, Jeremie Boucher, Senad Divanovic, Miguel A. Lanaspa, Richard J. Johnson, C. Ronald Kahn
In addition to stimulating lipogenic transcription factors, tracer studies show that fructose carbons can be immediately utilized as substrate in lipogenesis, whereas carbons labeled in glucose molecule are not observed to enter lipids, at least during a short four-hour observation period [31]. The difference in carbon appearance can be explained by increased flux through the fructolysis pathway. Glyceraldehyde-3 phosphate (GA3P) and dihydroxyacetone phosphate (DHAP) are common intermediates of both glycolysis and fructolysis pathways, downstream of which glucose and fructose metabolism is indistinguishable. However, prior to formation of these intermediates fructose is metabolized by KHK and aldolase, both of which are not regulated by insulin or end products of fructolysis. On the other hand, phosphofructokinase, an upstream enzyme in glycolysis pathway, is inhibited by both ATP and citrate [43], which are the products of this pathway. Thus, while both fructose and glucose carbons converge onto a common pathway, fructolysis is not subjected to feedback inhibition and allows for unrestrained flux through the pathway.
AK-1, a Sirt2 inhibitor, alleviates carbon tetrachloride-induced hepatotoxicity in vivo and in vitro
Published in Toxicology Mechanisms and Methods, 2020
Zixiong Zhou, Jing Qi, Jong-Won Kim, Myung-jo You, Chae Woong Lim, Bumseok Kim
As previously described (Roh et al. 2018), total RNAs were isolated from tissues using Easy-Spin Total RNA extraction kit (GeneAll, Seoul, Korea), according to the manufacturer’s instructions. Following incubation with DNase I containing RNase inhibitor (TOYOBO, Osaka, Japan), samples were transcribed using ReverTra Ace® qPCR RT Master Mix (TOYOBO), according to the manufacturer’s instructions. qRT-PCR was performed in the CFX96™ Real-Time PCR Detection System (Bio-Rad Laboratories, Hercules, CA), using SYBR® Green (TOYOBO). After the reaction was complete, specificity was verified by melting curve analysis. Relative quantification was performed by normalizing the value of glyceraldehyde-3-phosphate dehydrogenase. Table 1 summarizes the PCR primers used in this study.