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Inhibition of enzymes by metal ion-chelating reagents. The action of copper-chelating reagents on diamine oxidase.

ABSTRACT: 1. The inhibition of diamine oxidase has been studied by using the following copper-chelating reagents: 1,10-phenanthroline; 2,2'-bipyridyl; 8-hydroxyquinoline (oxine); diethyldithiocarbamate and dithio-oxamide (rubeanic acid). 2. Addition of chelating reagent caused a rapid inhibition of enzyme to a degree dependent solely on the final inhibitor concentration. Addition of substrate gave linear initial rates of reaction showing that under these conditions the inhibition was not being rapidly reversed. 3. The inhibition has been investigated by using new graphical methods and has been found in all cases to involve the chelating agents completely removing two Cu(2+) ions from the enzyme. An alternative possibility, involving ligand substitution, was eliminated. 4. A value of K=8.0x10(-33)m(-2) has been found for the enzyme in equilibrium with 2 Cu(2+) ions (i.e. beta(2), the stability constant for diamine oxidase/two Cu(2+), is 32.1).

SUBMITTER: Bardsley WG

PROVIDER: S-EPMC1166080 | biostudies-other | 1974 Jan

REPOSITORIES: biostudies-other

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Inhibition of enzymes by metal ion-chelating reagents. Theory and new graphical methods of study.

Project description:1. The mechanism of inhibition of enzymes by metal ion-chelating reagents is discussed and equations derived. 2. Two distinct mechanisms are postulated and graphical methods are given for differentiating between them. 3. Where the metal ion is actually removed from the enzyme to form a co-ordination complex in solution, a procedure is described for obtaining the stability constant for metal-enzyme interaction, the number of metal ions involved and the stoicheiometry of metal ion-ligand interaction.

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Structure and inhibition of human diamine oxidase.

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Inhibition of pig kidney diamine oxidase by substrate analogues.

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Genetic incorporation of a metal-ion chelating amino acid into proteins as a biophysical probe.

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Dual-target anti-Alzheimer's disease agents with both iron ion chelating and monoamine oxidase-B inhibitory activity.

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The inhibition of human placental diamine oxidase by substrate analogues.

Project description:1. The oxidation of p-dimethylaminomethylbenzylamine by purified placental diamine oxidase was followed by measuring the change in E(250) caused by the production of p-dimethylaminomethylbenzaldehyde. 2. The inhibition of this reaction by substrate analogues such as isothiouronium, guanidinium, dimethylsulphonium and trimethylammonium compounds was extensively studied. 3. The type and degree of inhibition by mono- and bis-onium compounds is described, and a theory is developed to explain the type of inhibition produced.

| S-EPMC1166265 | biostudies-other

In Vitro Antioxidant versus Metal Ion Chelating Properties of Flavonoids: A Structure-Activity Investigation.

Project description:Natural flavonoids such as quercetin, (+)catechin and rutin as well as four methoxylated derivatives of quercetin used as models were investigated to elucidate their impact on the oxidant and antioxidant status of human red blood cells (RBCs). The impact of these compounds against metal toxicity was studied as well as their antiradical activities with DPPH assay. Antihemolytic experiments were conducted on quercetin, (+)catechin and rutin with excess of Fe, Cu and Zn (400 ?M), and the oxidant (malondialdehyde, carbonyl proteins) and antioxidant (reduced glutathione, catalase activity) markers were evaluated. The results showed that Fe and Zn have the highest prooxidant effect (37 and 33% of hemolysis, respectively). Quercetin, rutin and (+)catechin exhibited strong antioxidant properties toward Fe, but this effect was decreased with respect to Zn ions. However, the Cu showed a weak antioxidant effect at the highest flavonoid concentration (200 ?M), while a prooxidant effect was observed at the lowest flavonoid concentration (100 ?M). These results are in agreement with the physico-chemical and antiradical data which demonstrated that binding of the metal ions (for FeNTA: (+)Catechin, KLFeNTA = 1.6(1) × 106 M-1 > Rutin, KLFeNTA = 2.0(9) × 105 M-1 > Quercetin, KLFeNTA = 1.0(7) × 105 M-1 > Q35OH, KLFeNTA = 6.3(8.7) × 104 M-1 > Quercetin3'4'OH and Quercetin 3OH, KLFeNTA ~ 2 × 104 M-1) reflects the (anti)oxidant status of the RBCs. This study reveals that flavonoids have both prooxidant and antioxidant activity depending on the nature and concentration of the flavonoids and metal ions.

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DFT Exploration of Metal Ion-Ligand Binding: Toward Rational Design of Chelating Agent in Semiconductor Manufacturing.

Project description:Chelating agents are commonly employed in microelectronic processes to prevent metal ion contamination. The ligand fragments of a chelating agent largely determine its binding strength to metal ions. Identification of ligands with suitable characteristics will facilitate the design of chelating agents to enhance the capture and removal of metal ions from the substrate in microelectronic processes. This study employed quantum chemical calculations to simulate the binding process between eleven ligands and the hydrated forms of Ni2+, Cu2+, Al3+, and Fe3+ ions. The binding strength between the metal ions and ligands was quantified using binding energy and binding enthalpy. Additionally, we explored the binding interaction mechanisms and explained the differences in binding abilities of the eleven ligands using frontier molecular orbitals, nucleophilic indexes, electrostatic potentials, and energy decomposition calculations based on molecular force fields. Based on our computational results, promising chelating agent structures are proposed, aiming to guide the design of new chelating agents to address metal ion contamination issues in integrated circuit processes.

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Inhibition of aminoglycoside acetyltransferase resistance enzymes by metal salts.

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