Author
Elena V. Schmalhausen
Bio: Elena V. Schmalhausen is an academic researcher from Moscow State University. The author has contributed to research in topics: Glyceraldehyde 3-phosphate dehydrogenase & Dehydrogenase. The author has an hindex of 14, co-authored 49 publications receiving 651 citations.
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TL;DR: It is shown that incubation of a mixture of purified glycolytic enzymes, as well as a muscle extract, in the presence of 10‐100 μMH 2 O 2 was shown to result in an increase in the rate of gly colysis, which really caused uncoupling of oxidation and phosphorylation in glyCOlysis.
Abstract: Summary Ine uence of H2O2 on glycolysis was investigated. A hypothesis previously formulated was tested according to which a mild oxidation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) results in uncoupling of oxidation and phosphorylation at this step ofglycolysisduetoacylphosphataseactivityoftheoxidizedenzyme. Incubation of a mixture of purie ed glycolytic enzymes, as well as a muscleextract,inthepresenceof10‐100 πMH2O2 wasshowntoresult inan increase in the rate ofglycolysis. The level oflactateaccumulation in the oxidized samples increased by 80‐150% compared to the samples containing mercaptoethanol. No ATP was formed by the H2O2-stimulated glycolysis. Thus, H2O2 really caused uncoupling of oxidation and phosphorylation in glycolysis. A role of GAPDH oxidation in regulation of glycolysis is discussed. IUBMBLife, 51: 309‐314, 2001
56 citations
TL;DR: It was demonstrated that non-native forms of GAPDH obtained by different ways efficiently bind to soluble amyloid-beta peptide (1-42) yielding a stable complex.
49 citations
TL;DR: The hydrogen peroxide‐induced ‘non‐phosphorylating’ activity of GAPDH is shown to be a result of the successive action of two forms of the enzyme subunits: one catalyzing production of 1,3‐bisphosphoglycerate, and the other performing its hydrolytic decomposition.
44 citations
TL;DR: It is observed that GAPDH activity was significantly decreased in the brain samples from TG mice and the infusion of LPS and IFNgamma, which can influence the progression of the AD, significantly reduced the enzyme activity.
37 citations
TL;DR: The denatured GAPDH forms were shown to interact directly with amyloidogenic proteins and to play a crucial role in blocking of chaperone system and to confirmation of the hypothesis on blocking of the chaperones by misfolded protein forms.
35 citations
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TL;DR: The types of low-molecular-weight thiols present in high concentrations in most cells, as well as the ways in which modifications of cysteinyl residues can impart or regulate molecular functions important to cellular processes, including signal transduction are summarized.
676 citations
TL;DR: The nature of ROS-induced damage on key cellular targets of oxidative stress is examined and evidence implicating ROS in clinically relevant, drug-related side effects including doxorubicin-induced cardiac damage, azidothymidine-induced myopathy, and cisplatin-induced ototoxicity is reviewed.
Abstract: Reactive oxygen species (ROS) are a byproduct of normal metabolism and have roles in cell signaling and homeostasis. Species include oxygen radicals and reactive nonradicals. Mechanisms exist that regulate cellular levels of ROS, as their reactive nature may otherwise cause damage to key cellular components including DNA, protein, and lipid. When the cellular antioxidant capacity is exceeded, oxidative stress can result. Pleiotropic deleterious effects of oxidative stress are observed in numerous disease states and are also implicated in a variety of drug-induced toxicities. In this paper, we examine the nature of ROS-induced damage on key cellular targets of oxidative stress. We also review evidence implicating ROS in clinically relevant, drug-related side effects including doxorubicin-induced cardiac damage, azidothymidine-induced myopathy, and cisplatin-induced ototoxicity.
542 citations
TL;DR: The data indicate that glucose provides ATP to F0F1-ATPase via glycolysis, enabling proton exclusion and thereby enhancing survival during gastric transit.
Abstract: Lactobacillus rhamnosus GG is an industrially significant probiotic strain with proven health benefits. In this study, the effect of glucose on L. rhamnosus GG survival was analyzed in simulated gastric juice at pH 2.0. It was found that the presence of 19.4 mM glucose resulted in up to 6-log10-enhanced survival following 90 min of exposure. Further work with dilute HCl confirmed that glucose was the sole component responsible. Comparative analysis with other Lactobacillus strains revealed that enhanced survival was apparent in all strains, but at different pH values. The presence of glucose at concentrations from 1 to 19.4 mM enhanced L. rhamnosus GG survival from 6.4 to 8 log10 CFU ml−1 in simulated gastric juice. The mechanisms behind the protective effect of glucose were investigated. Addition of N′,N′-dicyclohexylcarbodiimide to simulated gastric juice caused survival to collapse, which was indicative of a prominent role in inhibition of F0F1-ATPase. Further work with neomycin-resistant mutants that exhibited 38% to 48% of the F0F1-ATPase activity of the parent confirmed this, as the survival in the presence of glucose of these mutants decreased 3 × 106-fold compared with the survival of the wild type (which had a viability of 8.02 log10 CFU ml−1). L. rhamnosus GG survival in acidic conditions occurred only in the presence of sugars that it could metabolize efficiently. To confirm the involvement of glycolysis in the glucose effect, iodoacetic acid was used to inhibit glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity. The reduction in GAPDH activity caused survival to decrease by 8.30 log10 CFU ml−1 in the presence of glucose. The data indicate that glucose provides ATP to F0F1-ATPase via glycolysis, enabling proton exclusion and thereby enhancing survival during gastric transit.
447 citations
TL;DR: The diversity of cysteine's multiple roles in vivo is equally as fascinating as it is promising for future biochemical and pharmacological research.
407 citations
TL;DR: Observations corroborates the view that in coryneform bacteria under oxygen deprivation conditions the major anaplerotic reaction is driven by the ppc gene product rather than by the pyC gene product, and intracellular NADH concentrations in C. glutamicum were observed to correlate to oxygen-deprived metabolic flows.
Abstract: Lactate and succinate were produced from glucose by Corynebacterium glutamicum under oxygen deprivation conditions without growth. Addition of bicarbonate to the reaction mixture le
352 citations