Nicotinamide adenine dinucleotide inhibition

Insects poisoned with rotenone exhibit a steady decline ia oxygen consumption and the iasecticide has been shown to have a specific action ia interfering with the electron transport iavolved ia the oxidation of reduced nicotinamide adenine dinucleotide (NADH) to nicotinamide adenine dinucleotide (NAD) by cytochrome b. Poisoning, therefore, inhibits the mitochondrial oxidation of Krebs-cycle iatermediates which is catalysed by NAD. 

Hendrickson CM, Bowden JA. 1976. In vitro inhibition of lactate dehydrogenase by insecticidal polychlorinated hydrocarbons I. Mechanism of inhibition Possible association of reduced nicotinamide adenine dinucleotide with mirex. J Agric Food Chem 24(2) 241-244. 

Boron also appears to be involved in redox metabolism in cell membranes. Boron deficiency was shown to inhibit membrane H -ATPase isolated from plant roots, and H -ATPase-associated proton secretion is decreased in boron-deficient cell cultures [71]. Other studies show an effect of boron on membrane electron transport reactions and the stimulation of plasma reduced nicotinamide adenine dinucleotide (NADH) oxidase upon addition of boron to cell cultures [72, 73]. NADH oxidase in plasma membrane is believed to play a role in the reduction of ascorbate free radical to ascorbate [74]. One theory proposes that, by stimulating NADH oxidase to keep ascorbate reduced at the cell wall-membrane interface, the presence of boron is important in... 

Mitomycin (mitomycin C, Mitocin-C, Mutamycin) is an antibiotic that is derived from a species of Streptomyces. It is sometimes classified as an alkylating agent because it can covalently bind to and cross-link DNA. Mitomycin is thought to inhibit DNA synthesis through its abihty to alkylate double-strand DNA and bring about interstrand cross-hnking. There is evidence that enzymatic reduction by a reduced nicotinamide-adenine dinucleotide phosphate (NADPH) dependent reductase is necessary to activate the drug. 

I I 3. The answer is c. (Hardman, pp 1243-1247.) Antimetabolites of folic acid such as methotrexate, which is an important cancer chemotherapeutic agent, exert their effect by inhibiting the catalytic activity of the enzyme dihydrofolate reductase. The enzyme functions to keep folic acid in a reduced state. The first step in the reaction is the reduction of folic acid to 7,8-dihydrofolic acid (FH2), which requires the cofactor nicotinamide adenine dinucleotide phosphate (NADPH). The second step is the conversion of FH2 to 5,6,7,8-tetrahydrofolic acid (FH ). This part of the reduction reaction requires nicotinamide adenine dinucleotide (NADH) or NADPH. The reduced forms of folic acid are involved in one-carbon transfer reactions that are required during the synthesis of purines and pyrimidine thymidylate. The affinity of methotrexate for dihydrofolate reductase is much greater than for the substrates of folic acid and FH2. The action of... 

Metabolism of ethanol by alcohol dehydrogenase and the microsomal ethanol-oxidizing system (MEOS). Alcohol dehydrogenase and aldehyde dehydrogenase are inhibited by fomepizole and disulfiram, respectively. NAD +, nicotinamide adenine dinucleotide NADPH, nicotinamide adenine dinucleotide phosphate. 

Triazine (e.g., atrazine, simazine) and substituted urea (e.g., diuron, monuron) herbicides bind to the plastoquinone (PQ)-binding site on the D1 protein in the PS II reaction center of the photosynthetic electron transport chain. This blocks the transfer of electrons from the electron donor, QA, to the mobile electron carrier, QB. The resultant inhibition of electron transport has two major consequences (i) a shortage of reduced nicotinamide adenine dinucleotide phosphate (NADP+), which is required for C02 fixation and (ii) the formation of oxygen radicals (H202, OH, etc.), which cause photooxidation of important molecules in the chloroplast (e.g., chlorophylls, unsaturated lipids, etc.). The latter is the major herbicidal consequence of the inhibition of photosynthetic electron transport. 

Time-dependent inhibition should be examined. A 30-minute preincubation (i.e., with nicotinamide adenine dinucleotide phosphate (NADPH) enzyme, and drug candidate prior to addition of the probe substrate) is recommended. 

Figure 17.4 The electron transport chain of mitochondria. Triangles indicate sites of inhibition by various compounds. Cyt, cytochrome ETF, electron transfer flavoprotein. (Reproduced with permission from Moreadith RW, Batshaw ML, Ohnishi T, Kerr D, Knox B, Jackson D, Hruben R, Olson J, Reynafarje B, Lehninger AL. Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis J Clin Invest 74 685-697, 1984.)...

In another example, a mixed monolayer composed of a photoisomerizabie component and an electrochemical catalyst was applied to switch the electrocatalytic properties of a modified eleetrode between ON and OFF states. A Au-electrode surface functionalized with a nitrospiropyran mono-layer and PQQ moieties incorporated into the monolayer was applied to control the electrocatalytic oxidation of 1,4-dihydri-P-nicotinamide adenine dinucleotide (NADH) by light. The positively charged nitromerocyanine-state interface resulted in the repulsion of Ca cations, which are promoters for the NADH oxidation by the PQQ, thus resulting in the inhibition of the electrocatalytic process. In the nitrospiropyran state, the monolayer does not prevent the association of the PQQ catalyst and promoter thus it provides efficient electrocatalytic oxidation of NADH. Similar outcomes have been achieved using a combination of the photo- and thermal effects resulting... 

Complexing of the ribose group of nicotinamide adenine dinucleotide (NAD) (3) is preferred electrostatically over that of reduced nicotinamide adenine dinucleotide (NADH), leading to inhibition of this coenzyme system [16]. 

Slama JT, Simmons AM (1989) Inhibition of NAD glycohydrolase and ADP-ribosyl transferases by carbocyclic analogues of oxidized nicotinamide adenine dinucleotide. In Biochemistry 28 7688-7693. 

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