Role of zinc in catalytic activity of carbonic anhydrase IX

Tu, Cong; Foster, Lauren M.; Alvarado, Andrea; McKenna, Robert; Silverman, David N.; Frost, Susan C.

doi:10.1016/j.abb.2012.03.017

Cited by 18 publications

(9 citation statements)

References 35 publications

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“…Superoxide dismutase, a Zn-dependent enzyme, provides antioxidant defense for the placenta ( Mistry and Williams, 2011 ), which may have reduced activity during instances of pregnancy complications such as stillbirth in humans. Furthermore, Zn ions are present at the active site of carbonic anhydrase, which is necessary for transport and regulation of carbon dioxide ( Tu et al, 2012 ). Vallet et al (2014) hypothesized that additional Zn may increase carbonic anhydrase activity which may, in turn, build resistance to high CO 2 concentrations during birth, and potentially improve chance of survival for piglets that would otherwise be stillborn.…”

Section: Resultsmentioning

confidence: 99%

Effects of supplementing late-gestation sow diets with zinc on preweaning mortality of pigs under commercial rearing conditions1

Holen

Urriola

Schwartz³

et al. 2020

Translational Animal Science

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The objective of this experiment was to determine preweaning survival of pigs when sows were supplemented with 3 dietary levels of zinc (Zn) in late gestation. Gilts and sows (n = 339) were assigned to 1 of 3 dietary treatments based on parity. Dietary treatments were 1) Control—sows fed a corn–soybean meal-based diet containing 125 ppm total supplemental Zn supplied by ZnSO4 (75 ppm Zn) and AvailaZn (50 ppm Zn, CON); 2) Intermediate—as Control + 240 ppm supplemental Zn as ZnSO4 (INT); and 3) High—as Control + 470 ppm supplemental Zn as ZnSO4 (HI). Final supplemental Zn concentrations of the 3 dietary treatments were 1) CON—125 ppm; 2) INT—365 ppm; and 3) HI—595 ppm. Sows received dietary treatments from about day 85 of gestation until farrowing. Individual piglet birth weights were recorded within 12 h of parturition. Instances of piglet mortality were recorded daily. The statistical model considered fixed effects of treatment and random effects of parity. Piglets from sows fed the INT diet had heavier (P < 0.05) birth weights than those fed CON (1.42 vs. 1.38 kg, respectively), while offspring from sows fed HI tended to have heavier (P < 0.10) birth weights (1.40 kg) than pigs from INT sows. Furthermore, incidence of low birth weight pigs was less (P < 0.05) for sows consuming INT compared with sows fed CON and HI. Despite differences in birth weight, there were no differences (P > 0.05) in total pigs born, born alive, or weaned, nor differences in individual piglet gain or weaning weight across treatments. Mortality of low birth weight pigs was lowest (P < 0.05) for offspring from sows fed HI (28.1%) compared with offspring from sows fed INT (36.1%) and CON (38.3%). Similarly, overall piglet mortality tended to decrease (P < 0.10) as dietary Zn content increased (CON: 15.0%, INT: 13.2%, and HI: 12.2%). A subset of pigs (n = 420, n = 140/treatment) were selected at weaning to evaluate effects of dietary treatment on postweaning performance. There were no significant effects of sow Zn supplementation on final body weight, days to market, or carcass characteristics of market pigs. Overall, effects of supplemental dietary Zn at 365 and 595 ppm in late gestation improved preweaning survival of low birth weight piglets and reduced overall preweaning mortality of piglets.

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Section: Resultsmentioning

confidence: 99%

Effects of supplementing late-gestation sow diets with zinc on preweaning mortality of pigs under commercial rearing conditions1

Holen

Urriola

Schwartz³

et al. 2020

Translational Animal Science

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“…Previously Frost and colleagues reported a K i value of 85.3 nM against extracellular CA for the fluorescent sulfonamide Cpd 5c in intact hypoxic MDA-MB-231 cells using the same 18 O exchange assay [ 31 ]. Extracellular CA activity of MDA-MB-231 cells was also significantly reduced by 1 μM acetazolamide [ 32 ]. The inhibitors VR16-09 and VD11-4-2 exhibited higher effect towards CA IX expressed in cellular models than previously reported compounds likely due to higher affinity.…”

Section: Resultsmentioning

confidence: 99%

Novel fluorinated carbonic anhydrase IX inhibitors reduce hypoxia-induced acidification and clonogenic survival of cancer cells

et al. 2018

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Human carbonic anhydrase (CA) IX has emerged as a promising anticancer target and a diagnostic biomarker for solid hypoxic tumors. Novel fluorinated CA IX inhibitors exhibited up to 50 pM affinity towards the recombinant human CA IX, selectivity over other CAs, and direct binding to Zn(II) in the active site of CA IX inducing novel conformational changes as determined by X-ray crystallography. Mass spectrometric gas-analysis confirmed the CA IX-based mechanism of the inhibitors in a CRISPR/Cas9-mediated CA IX knockout in HeLa cells. Hypoxia-induced extracellular acidification was significantly reduced in HeLa, H460, MDA-MB-231, and A549 cells exposed to the compounds, with the IC50 values up to 1.29 nM. A decreased clonogenic survival was observed when hypoxic H460 3D spheroids were incubated with our lead compound. These novel compounds are therefore promising agents for CA IX-specific therapy.

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“…Table 1 illustrates several of the enzymes most recently identified as zinc metalloenzymes in the continuing elucidation of their extent and functions in nature [7,8,9]. Meanwhile, studies on the active site of carbonic anhydrase, the first of the zinc metalloenzymes identified, and its mode of operation continue to advance six decades later [10]. …”

Section: Organic Chemistry Of Zincmentioning

confidence: 99%

Update on Zinc Biology

Solomons¹

2013

Ann Nutr Metab

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Zinc has become a prominent nutrient of clinical and public health interest in the new millennium. Functions and actions for zinc emerge as increasingly ubiquitous in mammalian anatomy, physiology and metabolism. There is undoubtedly an underpinning in fundamental biology for all of the aspects of zinc in human health (clinical and epidemiological) in pediatric and public health practice. Unfortunately, basic science research may not have achieved a full understanding as yet. As a complement to the applied themes in the companion articles, a selection of recent advances in the domains homeostatic regulation and transport of zinc is presented; they are integrated, in turn, with findings on genetic expression, intracellular signaling, immunity and host defense, and bone growth. The elements include ionic zinc, zinc transporters, metallothioneins, zinc metalloenzymes and zinc finger proteins. In emerging basic research, we find some plausible mechanistic explanations for delayed linear growth with zinc deficiency and increased infectious disease resistance with zinc supplementation.

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Role of zinc in catalytic activity of carbonic anhydrase IX

Cited by 18 publications

References 35 publications

Effects of supplementing late-gestation sow diets with zinc on preweaning mortality of pigs under commercial rearing conditions1

Effects of supplementing late-gestation sow diets with zinc on preweaning mortality of pigs under commercial rearing conditions1

Novel fluorinated carbonic anhydrase IX inhibitors reduce hypoxia-induced acidification and clonogenic survival of cancer cells

Update on Zinc Biology

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