Metabolic control and structure of glycolytic enzymes. IV. Nicotinamide adenine dinucleotide-dependent in vitro reversal of dissociation and possible in vivo control of yeast glyceraldehyde-3-phosphate dehydrogenase synthesis

Biochemistry ◽  
1969 ◽  
Vol 8 (7) ◽  
pp. 2795-2805 ◽  
Author(s):  
William C. Deal
Keyword(s):  
Metabolic Control ◽  
Nicotinamide Adenine Dinucleotide ◽  
Glycolytic Enzymes ◽  
Nicotinamide Adenine

scholarly journals Metabolism and biochemical properties of nicotinamide adenine dinucleotide (NAD) analogs, nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD)

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Keisuke Yaku ◽  
Keisuke Okabe ◽  
Maryam Gulshan ◽  
Kiyoshi Takatsu ◽  
Hiroshi Okamoto ◽  
...  
Keyword(s):  
Stress Responses ◽  
Nicotinamide Adenine Dinucleotide ◽  
Biochemical Properties ◽  
Nicotinamide Adenine ◽  
Repair Gene ◽  
Nad Metabolism ◽  
Nad Glycohydrolase ◽  
Dna Repair Gene

Abstract Nicotinamide adenine dinucleotide (NAD) is an important coenzyme that regulates various metabolic pathways, including glycolysis, β-oxidation, and oxidative phosphorylation. Additionally, NAD serves as a substrate for poly(ADP-ribose) polymerase (PARP), sirtuin, and NAD glycohydrolase, and it regulates DNA repair, gene expression, energy metabolism, and stress responses. Many studies have demonstrated that NAD metabolism is deeply involved in aging and aging-related diseases. Previously, we demonstrated that nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD), which are analogs of NAD, are significantly increased in Nmnat3-overexpressing mice. However, there is insufficient knowledge about NGD and NHD in vivo. In the present study, we aimed to investigate the metabolism and biochemical properties of these NAD analogs. We demonstrated that endogenous NGD and NHD were found in various murine tissues, and their synthesis and degradation partially rely on Nmnat3 and CD38. We have also shown that NGD and NHD serve as coenzymes for alcohol dehydrogenase (ADH) in vitro, although their affinity is much lower than that of NAD. On the other hand, NGD and NHD cannot be used as substrates for SIRT1, SIRT3, and PARP1. These results reveal the basic metabolism of NGD and NHD and also highlight their biological function as coenzymes.

scholarly journals Extracellular Nicotinamide Adenine Dinucleotide Induces T Cell Apoptosis In Vivo and In Vitro

2001 ◽  
Vol 167 (9) ◽  
pp. 4942-4947 ◽  
Author(s):  
Zhang-Xu Liu ◽  
Olga Azhipa ◽  
Shigefumi Okamoto ◽  
Sugantha Govindarajan ◽  
Gunther Dennert
Keyword(s):  
T Cell ◽  
Nicotinamide Adenine Dinucleotide ◽  
Cell Apoptosis ◽  
Nicotinamide Adenine ◽  
T Cell Apoptosis

scholarly journals Proton export drives the Warburg Effect

2021 ◽  
Author(s):  
Shonagh Russell ◽  
Liping Xu ◽  
Yoonseok Kam ◽  
Dominique Abrahams ◽  
Bryce Ordway ◽  
...  
Keyword(s):  
Warburg Effect ◽  
Cancer Metabolism ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Glycolytic Enzymes ◽  
Hek293 Cells ◽  
Driver Mutations ◽  
The Warburg Effect

Aggressive cancers commonly ferment glucose to lactic acid at high rates, even in the presence of oxygen. This is known as aerobic glycolysis, or the “Warburg Effect”. It is widely assumed that this is a consequence of the upregulation of glycolytic enzymes. Oncogenic drivers can increase the expression of most proteins in the glycolytic pathway, including the terminal step of exporting H+ equivalents from the cytoplasm. Proton exporters maintain an alkaline cytoplasmic pH, which can enhance all glycolytic enzyme activities, even in the absence of oncogene-related expression changes. Based on this observation, we hypothesized that increased uptake and fermentative metabolism of glucose could be driven by the expulsion of H+ equivalents from the cell. To test this hypothesis, we stably transfected lowly-glycolytic MCF-7, U2-OS, and glycolytic HEK293 cells to express proton exporting systems: either PMA1 (yeast H+-ATPase) or CAIX (carbonic anhydrase 9). The expression of either exporter in vitro enhanced aerobic glycolysis as measured by glucose consumption, lactate production, and extracellular acidification rate. This resulted in an increased intracellular pH, and metabolomic analyses indicated that this was associated with an increased flux of all glycolytic enzymes upstream of pyruvate kinase. These cells also demonstrated increased migratory and invasive phenotypes in vitro, and these were recapitulated in vivo by more aggressive behavior, whereby the acid-producing cells formed higher grade tumors with higher rates of metastases. Neutralizing tumor acidity with oral buffers reduced the metastatic burden. Therefore, cancer cells with increased H+ export increase intracellular alkalization, even without oncogenic driver mutations, and this is sufficient to alter cancer metabolism towards a Warburg phenotype.

scholarly journals New Chemical Probe Targeting Bacterial NAD Kinase

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 4893
Author(s):  
David A. Clément ◽  
Clarisse Leseigneur ◽  
Muriel Gelin ◽  
Dylan Coelho ◽  
Valérie Huteau ◽  
...  
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Kinase Inhibitors ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Nicotinamide Adenine ◽  
Infection Model ◽  
Detailed Knowledge ◽  
Nad Kinase ◽  
Chemical Probe ◽  
Covalent Coupling

Nicotinamide adenine dinucleotide (NAD) kinases are essential and ubiquitous enzymes involved in the tight regulation of NAD/nicotinamide adenine dinucleotide phosphate (NADP) levels in many metabolic pathways. Consequently, they represent promising therapeutic targets in cancer and antibacterial treatments. We previously reported diadenosine derivatives as NAD kinase inhibitors with bactericidal activities on Staphylococcus aureus. Among them, one compound (namely NKI1) was found effective in vivo in a mouse infection model. With the aim to gain detailed knowledge about the selectivity and mechanism of action of this lead compound, we planned to develop a chemical probe that could be used in affinity-based chemoproteomic approaches. Here, we describe the first functionalized chemical probe targeting a bacterial NAD kinase. Aminoalkyl functional groups were introduced on NKI1 for further covalent coupling to an activated SepharoseTM matrix. Inhibitory properties of functionalized NKI1 derivatives together with X-ray characterization of their complexes with the NAD kinase led to identify candidate compounds that are amenable to covalent coupling to a matrix.

NAD(P)H oxidase–dependent platelet superoxide anion release increases platelet recruitment

Blood ◽  
2002 ◽  
Vol 100 (3) ◽  
pp. 917-924 ◽  
Author(s):  
Florian Krötz ◽  
Hae Young Sohn ◽  
Torsten Gloe ◽  
Stefan Zahler ◽  
Tobias Riexinger ◽  
...  
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Thrombus Formation ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Human Platelets ◽  
Nicotinamide Adenine ◽  
Irreversible Aggregation ◽  
Reduced Nicotinamide Adenine Dinucleotide ◽  
Specific Peptide

Abstract Platelets, although not phagocytotic, have been suggested to release O2−. Since O2−-producing reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidases can be specifically activated by certain agonists and are found in several nonphagocytotic tissues, we investigated whether such an enzyme is the source of platelet-derived O2−. We further studied which agonists cause platelet O2−release and whether platelet-derived O2− influences thrombus formation in vitro. Collagen, but not adenosine 5′-diphosphate (ADP) or thrombin, increased O2− formation in washed human platelets. This was a reduced nicotinamide adenine dinucleotide (NADH)–dependent process, as shown in platelet lysates. Consistent with a role of a platelet, NAD(P)H oxidase expression of its subunits p47phox and p67phoxand inhibition of platelet O2− formation by diphenylene-iodoniumchloride (DPI) and by the specific peptide-antagonist gp91ds-tat were observed. Whereas platelet-derived O2− did not influence initial aggregation, platelet recruitment to a preformed thrombus following collagen stimulation was significantly attenuated by superoxide dismutase (SOD) or DPI. It was also inhibited when ADP released during aggregation was cleaved by the ectonucleotidase apyrase. ADP in supernatants of collagen-activated platelets was decreased in the presence of SOD, resulting in lower ADP concentrations available for recruitment of further platelets. Exogenous O2−increased ADP- concentrations in supernatants of collagen-stimulated platelets and induced irreversible aggregation when platelets were stimulated with otherwise subthreshold concentrations of ADP. These results strongly suggest that collagen activation induces NAD(P)H oxidase–dependent O2− release in platelets, which in turn enhances availability of released ADP, resulting in increased platelet recruitment.

Sign in / Sign up

Export Citation Format

Share Document