Multiphoton imaging of the retina
Pablo Artal in Handbook of Visual Optics, 2017
Coenzymes such as NAD(P)H and flavoproteins like FAD are crucial for mitochondria-based cellular respiration pathways such as oxidative phosphorylation. Many retinal layers are densely packed with mitochondria because the retina is more metabolically active than the brain per unit weight (Wong-Riley, 2010). These molecules are of critical importance for cell survival and play the following roles during cellular respiration: NADH and NADPH are the reduced forms of the coenzymes nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+), respectively, and serve as reducing agents. NADH, a key component of cellular respiration, is generated in the cytoplasm during glycolysis. It is also produced in the mitochondria by the Krebs cycle (also known as the citric acid cycle) during aerobic respiration. NADH donates electrons in complex I, the first stage of the electron transport chain (oxidative phosphorylation), which generates adenosine triphosphate (ATP), a unit of intracellular energy. Thus, glycolysis and the Krebs cycle produce NADH, while the electron transport chain consumes NADH.Flavin adenine dinucleotide (FAD) is also strongly fluorescent. FAD moves electrons between the Krebs cycle and complex II, the second stage of the electron transport chain. FAD is used during the Krebs cycle and produced during the electron transport chain.
The thiols glutathione, cysteine, and homocysteine in human immunodeficiency virus (HIV) infection
Ronald R. Watson in NUTRIENTS and FOODS in AIDS, 2017
Glutathione is a cysteine containing tripeptide (γ-glutamyl-cysteinyl-glycine) that is found in eukaryotic cells at millimolar concentrations and is regarded as the major intracellular redox buffering principle.10,11 Glutathione is the substrate of selenium-dependent glutathione peroxidase catalyzing detoxification of hydrogen peroxide and other oxidants while glutathione reductase catalyzes the regeneration of reduced from oxidized glutathione (Figure 3.1). Flavin adenine dinucleotide (FAD), which is synthesized from riboflavin (vitamin B2), is required as a cofactor for glutathione reductase. Another antioxidant enzyme, glutathione transferase, inactivates reactive electrophilic species11 and participates in the metabolism of such endogenous compounds as steroids and leukotrienes.10,11 Moreover, glutathione itself has antioxidant properties.18 Finally, GSH provides reducing power for the maintenance of other antioxidants, e.g., ascorbic acid (vitamin C), vitamin E, and β-carotene.10,11
Metabolism
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
Energy is generated from metabolic fuels (carbohydrates, fats and proteins) and from reduced molecules, which are oxidized to release energy. Oxidation involves removing electrons at high potential from the fuel molecules and transferring them to a lower potential, thus releasing energy. The removed electrons must be transferred to a suitable electron acceptor, which has to be transportable, soluble in water and generally available. In cells, oxygen is the electron acceptor used. Unfortunately, oxygen is too reactive to be the immediate oxidizing agent and, so, intermediates, nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD), are employed as carriers of electrons between the metabolic pathways and the site of oxygen consumption in mitochondria. NAD+ and FAD are reduced by the major metabolic pathways (e.g. glycolysis and citric acid (Krebs) cycle) to NADH + H+ and FADH2 and carry electrons to the electron transport chain. In the electron transport chain, the electrons are transferred through a series of carriers of lower potential until they finally combine with oxygen to form water. In this process, energy is released, and ATP is formed from adenosine diphosphate (ADP) by the process of oxidative phosphorylation (Figure 65.1).
Design, synthesis, and evaluation of 3,7-substituted coumarin derivatives as multifunctional Alzheimer’s disease agents
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Sheunopa C. Mzezewa, Sylvester I. Omoruyi, Luke S. Zondagh, Sarel F. Malan, Okobi E. Ekpo, Jacques Joubert
Similarly, in contrast to MAO-A, the elongated nature of the MAO-B active site allows for better accommodation of the 3-propargylamine derivatives 6 and 7. It was observed that both compounds were able to interact with the crucial flavin adenine dinucleotide (FAD) cofactor to varying extents due to the inclusion of the propargylamine moiety. The FAD cofactor is essential for substrate catalysis and thus compounds that can come into close proximity or bind to this cofactor are known to inhibit the enzyme function to a greater extent42. Compound 6 maintains the previously mentioned π–H bonding with Cys 172 as well as its propargylamine moiety orienting in close proximity to FAD. Compound 7’s propargylamine moiety forms crucial π–H bonds with the cofactor. From the low nanomolar IC50 and high SI values displayed by these compounds, the importance of the propargylamine moiety can be seen in its ability to produce highly potent and selective inhibitors of MAO-B (Figure 7) .
Genetically modified Pichia pastoris, a powerful resistant factory for gold and palladium bioleaching and nanostructure heavy metal biosynthesis
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2020
Fatemeh Elahian, Razieh Heidari, Vahid Reza Charghan, Elham Asadbeik, Seyed Abbas Mirzaei
The previous study represented that engineered Pichia pastoris is an efficient option for the silver and selenium uptake and biotransformation. Cytochrome-b5 reductase arms Pichia to be a metal-resistant cell and to survive in high concentrations of the heavy metal ions. NADH-dependent reductase enzyme mediates the electron transport from NADH to a single FAD group. Then, the prosthetic FAD domain directly catalyzes the stoichiometric transfer of reducing equivalents, electrons, to the small heavy metal ion partners. Such engineered yeast usage for nanoparticle productions gain several advantages over physicochemical methods, immobilized enzyme bioreactors and non-transformed factory cells due ease of use, automation and the cell manipulation, inexpensive growth requirements and investment, simple scaling-up, high biomass yield, time-/cost-effectiveness, cofactors' needless and eco-friendliness. On the other hand, biosynthetic routes could provide good control over the recombinant enzyme production in the cell and consequently size distribution of nanoparticles than some of the physicochemical methods. Such properties introduced the developed microorganism as an excellent tool in nanotechnology science [16,21–24].
Personalized Nutrition: Translating the Science of NutriGenomics Into Practice: Proceedings From the 2018 American College of Nutrition Meeting
Published in Journal of the American College of Nutrition, 2019
Okezie I Aruoma, Sharon Hausman-Cohen, Jessica Pizano, Michael A. Schmidt, Deanna M. Minich, Yael Joffe, Sebastian Brandhorst, Simon J. Evans, David M. Brady
DHFR is greatly inhibited by the synthetic folic acid, which has similar effects to the anticancer drug methotrexate which inhibits DHFR to stave off growth and proliferation of cancer cells via decreasing thymine production by rapidly dividing cancer cells (13). When polymorphisms to DHFR are found this SNP may be bypassed by folinic acid. The prescription folinic acid, Leucovorin, “does not require reduction by DHFR to participate in reactions in which folates are used as a source of 1-carbon moieties” (14). Validation of DHFR SNP activity is accomplished by assessing formiminoglutamate (FIGLU), which increases when THF is insufficient. While there are several other enzymes in 1C metabolism, none are as well studied as methylene tetrahydrofolate reductase (MTHFR). This enzyme has two genetic variants, C677T and A1298C, of which the former increases homocysteine and the latter does not. This enzyme requires as its co-factors the riboflavin-derived FAD, NADH, and ATP. Polymorphisms to MTHFR are associated with increased risk for neural tube defects, miscarriage, dementia, mood disorders, peripheral artery disease, colon cancer, and leukemia (15). This enzyme is used to convert 5, 10-methylene THF to L-methylfolate. This newly generated methyl donor is then donated to the methylation cycle where, via methionine synthase (MTR) and methionine synthase reductase (MTRR), it is used to methylate vitamin B12 and ultimately contributes to the formation of the universal methyl donor S-adenosylmethyionine.
Related Knowledge Centers
- Biochemistry
- Cofactor
- Flavin Mononucleotide
- Flavoprotein
- Protein
- Pyruvate Dehydrogenase Complex
- Metabolism
- Redox
- Flavin Group
- Amine Oxide