Zinc nutrition and dietary zinc supplements

Duan, Maoping; Tian, Li; Liu, Bo; Yin, Shuhua; Zang, Jiachen; Lv, Chenyan; Zhao, Guanghua; Zhang, Tuo

doi:10.1080/10408398.2021.1963664

Cited by 37 publications

(20 citation statements)

References 186 publications

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“…Despite decades of diverse applications of zinc supplements in human health, the details of bioavailability, pharmacokinetics, pharmacodynamics, and potential toxicities of the dietary zinc are still controversial ( 50 , 70 ). Multiple factors confound the efficiency of zinc absorption from the gut, its penetration through the blood-brain barrier, and the ultimate entry and activities within neuronal cells ( 50 , 71 , 72 ).…”

Section: Discussionmentioning

confidence: 99%

Restoration of the GTPase activity and cellular interactions of Gα _o mutants by Zn ²⁺ in GNAO1 encephalopathy models

et al. 2022

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De novo point mutations in GNAO1 , gene encoding the major neuronal G protein Gα o , have recently emerged in patients with pediatric encephalopathy having motor, developmental, and epileptic dysfunctions. Half of clinical cases affect codons Gly 203 , Arg 209 , or Glu 246 ; we show that these mutations accelerate GTP uptake and inactivate GTP hydrolysis through displacement Gln 205 critical for GTP hydrolysis, resulting in constitutive GTP binding by Gα o . However, the mutants fail to adopt the activated conformation and display aberrant interactions with signaling partners. Through high-throughput screening of approved drugs, we identify zinc pyrithione and Zn 2+ as agents restoring active conformation, GTPase activity, and cellular interactions of the encephalopathy mutants, with negligible effects on wild-type Gα o . We describe a Drosophila model of GNAO1 encephalopathy where dietary zinc restores the motor function and longevity of the mutant flies. Zinc supplements are approved for diverse human neurological conditions. Our work provides insights into the molecular etiology of GNAO1 encephalopathy and defines a potential therapy for the patients.

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Section: Discussionmentioning

confidence: 99%

Restoration of the GTPase activity and cellular interactions of Gα _o mutants by Zn ²⁺ in GNAO1 encephalopathy models

et al. 2022

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“…It can be found that the amount of zinc ion increases rapidly in the initial phase and then increases slowly as the time goes by, which is due to the fast dissolution of the gelatin/ZnSO 4 electrolyte in simulated gastric acid at the beginning, as illustrated in Figure b and Figure S18. The total accumulated amount of zinc ion for a completely decomposed single e-ZMSC device (including Zn microanode and ZnSO 4 electrolyte) is approximately 4.58 mg, which is lower than the upper limit of 40 mg in 1 day, , conforming to the level of over-the-counter zinc supplements.…”

Section: Resultsmentioning

confidence: 84%

An Edible and Nutritive Zinc-Ion Micro-supercapacitor in the Stomach with Ultrahigh Energy Density

et al. 2022

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Miniature energy storage devices simultaneously combining high energy output and bioavailability could greatly promote the practicability of green, safe, and nontoxic in vivo detection, such as for noninvasive monitoring or treatment in the gastrointestinal tract, which is still challenging. Herein, we report ingestible and nutritive zinc-ion-based hybrid micro-supercapacitors (ZMSCs) consisting of an edible active carbon microcathode and zinc microanode, which can be inserted into a standard-sized capsule and ingested in a pig stomach. With features including flexibility, light weight, and shape adaptability, a single microdevice displays a high energy density of 215.1 μWh cm–2, superior to that of state-of-the-art biocompatible SCs/MSCs and even traditional ZMSCs reported previously. It also delivers an areal capacitance of 605 mF cm–2 and a high working voltage of 1.8 V, exceeding that of miniaturized commercial button batteries (1.55 V, RENATA 337). Comprehensive studies in vivo and in vitro demonstrate that the ZMSCs with high biocompatibility and safety not only power electronic equipment in the porcine stomach without a voltage booster but also act as a nutritional supplement of trace element zinc within the dose range, as well as the ability of potent antibacterial activity against bacterium Escherichia coli during the discharging process. This work provides an example for the design and fabrication of edible energy storage devices with high performance.

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“…Despite decades of diverse applications of zinc supplements in human health, the details of bioavailability, pharmacokinetics, pharmacodynamics, and potential toxicities of the dietary zinc are still controversial 41,50 . Multiple factors confound the e ciency of zinc absorption from the gut, its penetration through the blood-brain barrier, and the ultimate entry and activities within neuronal cells 41,51,52 .…”

Section: Discussionmentioning

confidence: 99%

Restoration of the GTPase activity of Gαo mutants by Zn2+ in GNAO1 encephalopathy models

Larasati¹,

Savitsky²,

Koval³

et al. 2021

Preprint

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GNAO1 encephalopathy is a rare pediatric disease characterized by motor dysfunction, developmental delay, and epileptic seizures1-3. De novo point mutations in the gene encoding Gαo, the major neuronal G protein, lie at the core of this dominant genetic malady4. Half of the clinical case mutations fall on codons Gly203, Arg209, or Glu246 near the GTP binding/hydrolysis pocket of Gαo1-3. We here show that these pathologic mutations strongly speed up GTP uptake and inactivate GTP hydrolysis by Gαo, resulting in constitutive GTP binding by the G protein. Molecular dynamics simulations indicate that the mutations cause displacement of Gln205, the key to GTP hydrolysis. Decreased interactions with cellular partners including RGS19 suggest that despite the enhanced GTP residence, the mutants fail to fully adopt the activated conformation and thus transmit the signal. Through a high-throughput screening of approved drugs aiming at correction of this core biochemical dysfunction, we identify zinc pyrithione and Zn2+ ions as agents restoring the active conformation, GTPase activity, and cellular interactions of the encephalopathy mutants, with a negligible effect on wild type Gαo. We describe a Drosophila model of GNAO1 encephalopathy and show that dietary zinc supplementation restores the motor function and longevity of the mutant flies. With zinc supplements frequently recommended for diverse human neurological conditions, our work spanning from identification of the core biochemical defect in Gαo mutants and cellular interactions analysis to high-throughput screening and animal validation of the deficiency-correcting drug defines the potential therapy for GNAO1 encephalopathy patients.

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Zinc nutrition and dietary zinc supplements

Cited by 37 publications

References 186 publications

Restoration of the GTPase activity and cellular interactions of Gα _o mutants by Zn ²⁺ in GNAO1 encephalopathy models

Restoration of the GTPase activity and cellular interactions of Gα _o mutants by Zn ²⁺ in GNAO1 encephalopathy models

An Edible and Nutritive Zinc-Ion Micro-supercapacitor in the Stomach with Ultrahigh Energy Density

Restoration of the GTPase activity of Gαo mutants by Zn2+ in GNAO1 encephalopathy models

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Zinc nutrition and dietary zinc supplements

Cited by 37 publications

References 186 publications

Restoration of the GTPase activity and cellular interactions of Gα o mutants by Zn 2+ in GNAO1 encephalopathy models

Restoration of the GTPase activity and cellular interactions of Gα o mutants by Zn 2+ in GNAO1 encephalopathy models

An Edible and Nutritive Zinc-Ion Micro-supercapacitor in the Stomach with Ultrahigh Energy Density

Restoration of the GTPase activity of Gαo mutants by Zn2+ in GNAO1 encephalopathy models

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Product

Resources

About

Restoration of the GTPase activity and cellular interactions of Gα _o mutants by Zn ²⁺ in GNAO1 encephalopathy models

Restoration of the GTPase activity and cellular interactions of Gα _o mutants by Zn ²⁺ in GNAO1 encephalopathy models