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The Bioenergetics of Mammalian Sperm Motility
Published in Claude Gagnon, Controls of Sperm Motility, 2020
Neither α-chlorohydrin nor the 6-chloro-6-deoxysugars will inhibit glyceraldehyde 3-phosphate dehydrogenase themselves and the active intermediate is probably the oxidation product 3-chlorolactaldehyde, which has the appropriate chiral conformation to act as an analogue of the substrate glyceraldehyde 3-phosphate.169 3-Chlorolactaldehyde can also inhibit triose phosphate isomerase (Figure 8).170
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
In the UV method aldolase reaction is coupled with two other enzyme reactions [Eqs. (20)-(22)]. Triosephosphate isomerase (TIM) is added to ensure rapid conversion of all glyceraldehyde-3-phosphate (GAP) to dihydroxyacetone phosphate (DAP). Glycerol-3-phosphate dehydrogenase (GDH) is added to reduce DAP to glycerol-3-phosphate, with NADH acting as hydrogen donor (Pinto et al., 1969b).
Biocatalyzed Synthesis of Antidiabetic Drugs
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Recently, the use of smart E. coli synthetic factory for synthesizing iminosugars have been described (Wei et al., 2015), through the transformation of DHAP-dependent aldolase-mediated in vitro reactions into engineered E. coli for facile and effective production of polyhydroxylated molecules (Fig. 11.43, 125). In glycolysis, glucose is converted into fructose 1,6-bisphosphate via three enzymatic steps and subsequently split by FruA into two interconvertible triose phosphates, DHAP and d-glyceraldehyde-3-phosphate (GAP), in a concentration ratio of DHAP to GAP is 96% to 4% because of the favored formation of DHAP by triose-phosphate isomerase (TIM). Thus, these authors introduced and overexpressed an aldolase gene and a phosphatase gene in E. coli cells, generating a synthetic factory named E. coli FruA-Y, so that the overexpressed aldolase could hijack DHAP from the glycolytic pathway and couple it with exogenous aldehyde 124 to furnish a phosphorylated aldol adduct, which is in situ dephosphorylated by the overexpressed phosphatase and released from the host cell to give the desired product (Fig. 11.43). Scheme of the modified glycolysis by an E. coli synthetic factory.
Screening tools for hereditary hemolytic anemia: new concepts and strategies
Published in Expert Review of Hematology, 2021
Elisa Fermo, Cristina Vercellati, Paola Bianchi
Hereditary hemolytic anemias may also be caused by deficiencies of enzymes of the erythrocyte metabolism, that is composed by three main pathways: glycolysis, the main source of metabolic energy in the erythrocytes, pentose phosphate pathway, and nucleotide metabolism. G6PD deficiency is the most widespread erythroenzymopathy, and is usually associated with acute hemolysis caused by oxidative stress, with the exception of the class-I variants, that result in chronic hemolytic anemia. Pyruvate kinase (PK) deficiency is the most frequent enzymopathy affecting glycolysis, followed by glucose ephosphate isomerase (GPI), whereas pyrimidine 5′-nucleotidase (P5′N) and adenylate kinase (AK) deficiency involve the nucleotide metabolism. Some enzymes, such as triose phosphate isomerase (TPI), phosphoglycerate kinase (PGK) and phosphofructokinase (PFK), are not confined to the red cells but also expressed in other tissues; in such cases, hemolytic anemia may be accompanied to non-hematological symptoms such as myopathy, neuromuscular impairment and mental retardation [5–7].
Interaction of low frequency external electric fields and pancreatic β-cell: a mathematical modeling approach to identify the influence of excitation parameters
Published in International Journal of Radiation Biology, 2018
Sajjad Farashi, Pezhman Sasanpour, Hashem Rafii-Tabar
The glycolysis pathway contains a series of reactions for converting glucose into pyruvate and ATP. In the first step glucose is phosphorylated and converted to glucose-6-phosphate (G6P) which will be isomerised to the fructose-6-phosphate (F6P). The further phosphorylation of F6P by phosphofructokinase-1 enzyme produces fructose 1,6-bisphosphate, which in the next step will be cleaved into glyceraldehyde-3-phosphate (G3P) and dihydroxy acetone phosphate (DHAP) using aldolase enzyme. The DHAP is converted to further G3P by triose-phosphate isomerase. This phase, the procedure is preparatory phase and requires energy consumption. In the next step G3P oxidized to 1,3-bisphosphoglycerate incorporating glyceraldehyde 3-phosphate dehydrogenase. A large amount of energy during the oxidation of an aldehyde group will be released. In this step Nicotinamide adenine dinucleotide (NAD+) will be reduced to NADH, the reduced form of NAD+. The enzyme phosphoglycerate kinase transfers the phosphoryl group of 1,3-bisphosphoglycerate to ADP and producing ATP and 3-phosphoglycerate which the latter will be isomerized to 2-phosphoglycerate using Phosphoglycerate mutase. Using the enzyme enolase, 2-phosphoglycerate will be converted to phosphoenolpyruvate (PEP). Finally, PEP will be converted to pyruvate by pyruvate kinase. In this step one extra ATP molecule will be produced. The glycolysis pathway is depicted in Figure 1.
Therapeutic targets for the treatment of microsporidiosis in humans
Published in Expert Opinion on Therapeutic Targets, 2018
Triosephosphate isomerase (TIM), which plays an important role in glycolysis of Enc. intestinalis, was analyzed as a drug target for the therapy of microsporidiosis [109]. TIM catalyzes the reversible interconversion of the triose phosphate isomers dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (GAP), and is essential for efficient energy production. Studies of TIM in Trypanosoma cruzi, T. brucei, Entamoeba histolytica, and Giardia duodenalis have demonstrated that modification of cysteine (Cys) residues by sulfhydryl reagents could change its function and structure, leading to inactivation of this enzyme [110–113]. As a proof of concept, three sulfhydryl reagents (MMTS, MTSES, and DTNB) were used to modify the conserved Cys in Enc intestinalis TIM (EiTIM). These three sulfhydryl reagents do not inactivate human triosephosphate isomerase despite [109,114]. Treatment with these compounds caused a significant reduction of EiTIM activity in a concentration-dependent manner. When EiTIM was inhibited the process of interconversion between DHAP and GAP was reduced, leading to an accumulation of either DHAP or GAP which are both toxic to the microsporidia spores (Figure 1(a)). A microsporidia lack the glyoxalase system, which can detoxify these compounds, the toxicity of TIM inhibition may be enhanced in microsporidia. Furthermore, three compounds that are widely used in the pharmaceutical industry (omeprazole, rabeprazole, and sulbutiamine) have also been demonstrated to modify EiTIM Cys residues and to significantly inactive EiTIM [98], providing lead compounds for the development of this therapeutic pathway. Overall, these data suggest TIM is a potential target for new therapeutic agents for microsporidiosis.