Interaction of Flavonoids with Zinc and Zinc-Containing Enzymes

Abstract

The current chelation therapy has several drawbacks, including lack of selectivity, which could lead to trace metal depletion. Consequently, the proper function of metalloenzymes can be disrupted. Flavonoids possess chelating properties and hence interfere with the homeostasis of essential metals. We focused on zinc, an important trace metal required for the function of many enzymes and transcription factors. After making an initial evaluation of the Zn 2+ -chelating properties of a series of flavonoids, the effect of these compounds on various zinc-containing enzymes was also investigated. We performed enzyme inhibition assays spectrophotometrically using yeast and equine alcohol dehydrogenases and bovine glutamate dehydrogenase. Nine of the 21 flavonoids tested were capable of chelating Zn 2+ . Baicalein and 3-hydroxyflavone were the most potent Zn 2+ chelators under slightly acidic and neutral pH conditions. This chelation was also confirmed by the ability to reverse Zn 2+ -induced enzymatic inhibition of bovine glutamate dehydrogenase. Although some flavonoids were also able to inhibit zinc-containing alcohol dehydrogenases, this inhibition was likely not caused by Zn 2+ chelation. Luteolin was a relatively potent inhibitor of these enzymes regardless of the presence of Zn 2+ . Docking studies confirmed the binding of active flavonoids to equine alcohol dehydrogenase without any significant interaction with the catalytic zinc.

Zinc-Rutin Particles Ameliorate DSS-Induced Acute and Chronic Colitis via Anti-inflammatory and Antioxidant Protection of the Intestinal Epithelial Barrier

“…The addition of ZnCl 2 deepened the color of flavonoid solutions, and the color returned to the same color as the flavonoid solutions after addition of EDTA (Figure B), indicating that a reversible metal–organic coordination reaction had occurred. This result was consistent with the reported literature that some flavonoids can chelate zinc ions . In the UV–vis spectrum of MYR and QCT, the addition of ZnCl 2 caused a new absorption band ranging from 415 to 470 nm, which disappeared after EDTA addition.…”

“…This result was consistent with the reported literature that some flavonoids can chelate zinc ions. 19 In the UV−vis spectrum of MYR and QCT, the addition of ZnCl 2 caused a new absorption band ranging from 415 to 470 nm, which disappeared after EDTA addition. Meanwhile, the new absorption band was not observed in UV−vis spectra of RT after ZnCl 2 addition (Figure 1C).…”

“…The prevalence of zinc deficiency in IBD patients ranges from 15 to 45%, and there is growing evidence that zinc supplementations can alleviate IBD as zinc deficiency exacerbates colonic inflammation , and mucosal barrier dysfunction . This phenomenon is due to the fact that approximately 3000 proteins in humans require zinc as a cofactor, which has a panoply of effects on immune function . Besides, zinc has been reported to increase resistance to diarrhea and gastrointestinal infections in vulnerable patients by exerting anti-inflammatory effects .…”

“…18 This phenomenon is due to the fact that approximately 3000 proteins in humans require zinc as a cofactor, which has a panoply of effects on immune function. 19 Besides, zinc has been reported to increase resistance to diarrhea and gastrointestinal infections in vulnerable patients by exerting anti-inflammatory effects. 20 Characterizations.…”

3-Hydroxyflavone is a mildly active and safe cobalt chelator while cobalt markedly enhances baicalein toxicity toward erythrocytes

“…There is currently no explanation for this phenomenon, but the nding is not isolated as differences in metal reduction as well as zinc chelation have been previously observed between this couple. 41,58 Very little is known about the stoichiometry of the cobalt-avonoid complexes. In the case of quercetin, three stoichiometries (1 : 1, 1 : 2 and 2 : 3, metal : avonoid) were suggested by electrospray ionization tandem mass spectrometry, 28 whereas 1 : 1 by potentiometry/UV-Vis spectrometry.…”