Niacin
Judy A. Driskell, Ira Wolinsky in Sports Nutrition, 2005
These coenzymes play a critical role in fast glycolysis, where NAD is reduced in the glyceraldehyde-3- phosphate to 1, 3 biphosphoglycerate step, and then the hydrogen ions are used in converting pyruvate to lactate (Figure 5.2). Under slow glycolysis these hydrogens are transported to the ETC. In the TCA cycle, NAD serves as an electron acceptor for a number of enzymes including pyruvate dehydrogenase, isocitrate dehydrogenase, α-ketogluterate dehydrogenase and malate dehydrogenase (Figure 5.3). The resulting NADH is then moved to the ETC to be reoxidized to NAD and generates ATP as a result (Figure 5.4).1–4
Mitochondrial Stress and Cellular Senescence
Shamim I. Ahmad in Handbook of Mitochondrial Dysfunction, 2019
NAD+ may also be regulated by controlling malate dehydrogenase activity (MDH). MDH1 is a component of the malate-aspartate shuttle that catalyzes the reduction of oxaloacetate to malate by converting NADH to NAD+ (Lee et al. 2012). Depleting MDH1 in young HDFs and IMR90 human fibroblast reduces NAD+/NADH ratio, inhibits SIRT1, and induces cellular senescence (Lee et al. 2012). Moreover, old human dermal fibroblasts (HDFs) have reduced MDH1 activity and cytosolic NAD+ levels.
Outdoor Air Pollution
William J. Rea, Kalpana D. Patel in Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
Mitochondria have a proteome of approximately 1500 proteins.221 Nearly 1000 of these proteins have catalytic functions in cell metabolism such as citrate synthase or malate dehydrogenase. Under normal physiologic conditions, the concentrations of thousands of nutrients and metabolic substrates in mitochondria are closely governed by the collective kinetic constants (Km, Kcat, V, Hill coefficient, etc.) of all the enzymes responsible for transforming those metabolites. This has recently been computationally modeled in the Recon 1 and BiGG reconstructions of cell and organ metabolism.222,223 Only the primary structure of an enzyme is genetically determined. The activity of an enzyme at any instant in time is determined by ambient metabolic conditions. The environmental triggering agents, for example, the Km of citrate synthase for oxaloacetate is approximately 2 μM, but the enzyme is allosterically inhibited by ATP, NADH, acetyl-CoA, palmitoyl-CoA, and the product citric acid so the rate of converting oxaloacetate to citrate is changing minute to minute according to the condition of the cell.224 When the concentrations of substrates are perturbed by viral or microbial infection, disease, toxin, or nutritional excess, mitochondria sense this as a metabolic mismatch between the optimum concentration of those metabolites for a given tissue and the actual concentration. Thus the chemically sensitive patient due to its varied metabolism responds differently at different times. At times, they have more resistance and other times are very vulnerable. This function at times makes treatment doses of antigens and nutrients difficult to deliver due to the need for varying doses. Of course, medications, nutrients, and interdermal neutralization at varying times are fixed doses and may not function at times of crises unless they are primed over weeks and months when the organism is stable.
Really does temperature reduction and norepinephrine have similar effects on the energy metabolism in rat brown adipose tissue?
Published in Archives of Physiology and Biochemistry, 2018
B. Sopeña, Z. López-Ibarra, A. J. López-Farré, N. de las Heras, S. Ballesteros, A. González-Cantalapiedra, V. Lahera, J. J. Zamorano-León
As previously we have reported (Modrego et al.2012, López-Ibarra et al.2015), proteins were separated on denaturing SDS-PAGE 15% (w/v) polyacrylamide gels by loading 20 μg/lane protein solubilised in Laemmli buffer containing 2-mercaptoethanol. After electrophoresis, proteins were blotted onto nitrocellulose membranes (Immobilion-P; Millipore, Billerica, MA), and then blocked overnight at 4 °C with 5% (w/v) albumin. Nitrocellulose membranes were then incubated with different antibodies against each of the aforementioned proteins. Indeed, CPT-I and CPT-II were determined using polyclonal antibodies (sc-20670 and sc-20526, respectively, dilution 1:1000; Santa Cruz Biotechnology, Inc., Santa Cruz, CA). Mitochondrial malate dehydrogenase and lactate dehydrogenase were determined using monoclonal antibodies (sc-1666879 and sc-133123, dilution 1:1000, Santa Cruz Biotechnology, Inc., Santa Cruz, CA). UCP-1 was determined using a polyclonal antibody (ab23841 dilution 1:1000, Abcam, Cambridge, UK). The core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (MT-ND1), cytochrome c oxidase and mitochondrial F1 ATP synthase α-chain were determined using monoclonal antibodies (ab181848, Abcam, Cambridge, UK; sc-58613, Santa Cruz Biotechnology, Inc., Santa Cruz, CA; ab14705 Abcam, Cambridge, UK, respectively; dilution 1:1000). Nitrocellulose was also incubated with a monoclonal anti-β-actin antibody (A-5441, Sigma-Aldrich, St. Louis, MO, dilution 1:1500) used as loading control.
Purification and characterisation of glutathione reductase from scorpionfish (scorpaena porcus) and investigation of heavy metal ions inhibition
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Glutathione reductase (EC 1.8.1.7; GR), a major enzyme in glutathione metabolism, is required for the maintenance of the reduced form of cellular glutathione, which is strongly nucleophilic for many reactive electrophiles10,11. The flavin enzyme GR acts as an antioxidant to protect cells from oxidative stress by reducing glutathione disulphide (GSSG) to its reduced form (GSH)12. It has an important role in the drug and detoxification mechanisms especially in the liver. This is due to the cytochrome P-450 system found in liver microsomes, which provides detoxifying events13. Maintaining the GSH/GSSG ratio in the cell environment is one of the most important known targets of the GR enzyme-catalysed reactions14. Glutathione reductase is involved in the reduction-oxidation of intracellular glutathione for GSSG, which is generated through the detoxification of hydroperoxides and reduction of some other chemicals catalysed by glutathione perdoxidase15. The NADP+ dependent malate dehydrogenase and pentose phosphate pathways provide the NADPH needed in this catalytic process16,17. NADPH, a key product of the pentose phosphate cycle, is employed extensively in reductive biosynthesis. Furthermore, it aids in the protection of the cell against oxidative damage9.
Responses to iron oxide and zinc oxide nanoparticles in echinoderm embryos and microalgae: uptake, growth, morphology, and transcriptomic analysis
Published in Nanotoxicology, 2020
Anne-Marie Genevière, Evelyne Derelle, Marie-Line Escande, Nigel Grimsley, Christophe Klopp, Christine Ménager, Aude Michel, Hervé Moreau
Of the 918 DE genes specific to ENPs (common to Fe2O3 and ZnO, not responding to ions), 7 (0.2%) were highly induced, with 3 having a predicted annotation: SfsA, a transcription factor involved in maltose metabolism, MFS1, a transporter of the Major Facilitator Superfamily and RCC1 a Regulator of Chromosome Condensation (Figure S7). Only one gene, MDH5, orthologous of the C. reinhardtii NADP-dependent malate dehydrogenase (EC 1.1.1.37) was highly repressed. In addition, the hsp90 genes encoding stress chaperone proteins were either specifically or more intensively altered by ENPs than their corresponding ions while ENPs specifically induced hsp20 expression. Two essential cell-cycle genes were also preferentially repressed in response to ENPs, albeit to a lesser extent (lower LFC), CDKD, the CDK activating kinase, and APC3 a subunit of the Anaphase Promoting Complex (Figure S7).
Related Knowledge Centers
- Dehydrogenase
- Enzyme
- Malate Dehydrogenase
- Malic Acid
- Metabolic Pathway
- Nicotinamide Adenine Dinucleotide
- Oxaloacetic Acid
- Citric Acid Cycle
- Reversible Reaction
- Redox