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Acetaldehyde Dehydrogenase

The Experts below are selected from a list of 306 Experts worldwide ranked by ideXlab platform

Yongdoo Park – 1st expert on this subject based on the ideXlab platform

  • functional study of Acetaldehyde Dehydrogenase 1 aldh1 in keratinocytes microarray integrating bioinformatics approaches
    Journal of Biomolecular Structure & Dynamics, 2020
    Co-Authors: Minwoo Park, Junmo Yang, Yongdoo Park, Guoying Qian

    Abstract:

    The function of Acetaldehyde Dehydrogenase 1 (ALDH1) has been gradually elucidated in several diseases, especially in various cancers. However, the role of ALDH1 in skin-related diseases has been m…

  • a computational integrating kinetic study on the flexible active site of human Acetaldehyde Dehydrogenase 1
    Process Biochemistry, 2016
    Co-Authors: Junmo Yang, Yingying Xu, Hee Seung Yang, Zhirong Lu, Hang Mu, Qian Zhang, Yongdoo Park

    Abstract:

    Abstract In order to gain more insight into the relation between the structure of Acetaldehyde Dehydrogenase 1 (ALDH1) and its catalytic and regional active site properties, the denaturant guanidine hydrochloride (GdnHCl) was employed in this study. The effects of GdnHCl on ALDH1 conformational and functional changes were evaluated by kinetic analysis and by performing computational molecular dynamics (MD) simulations. We found that direct binding of GdnHCl to ALDH1 induced complete inactivation prior to conspicuous changes in its tertiary structure or hydrophobic exposure, indicating that the active site is flexible compared to the overall structure. Kinetic experimental results and computational simulations indicated that there are specific sites on ALDH1 to which guanidine binds, resulting in blocking of catalytic function without a large degree of structural disruption. These sites may lay specifically in a cofactor-binding region, which was suggested by the observation of mixed-type inhibition. Our study provides insight into the flexibility of the ALDH1 active site through the use of GdnHCl denaturant and computational simulations to suggest possible binding mechanisms of inhibitors for the clinical applications.

  • integration of inhibition kinetics and molecular dynamics simulations a urea mediated folding study on Acetaldehyde Dehydrogenase 1
    Applied Biochemistry and Biotechnology, 2016
    Co-Authors: Yongdoo Park, Yingying Xu, Zhirong Lu, Hang Mu, Qian Zhang

    Abstract:

    Understanding the mechanism of Acetaldehyde Dehydrogenase 1 (ALDH1) folding is important because this enzyme is directly involved in several types of cancers and other diseases. We investigated the urea-mediated unfolding of ALDH1 by integrating kinetic inhibition studies with computational molecular dynamics (MD) simulations. Conformational changes in the enzyme structure were also analyzed using intrinsic and 1-anilinonaphthalene-8-sulfonate (ANS)-binding fluorescence measurements. Kinetic studies revealed that the direct binding of urea to ALDH1 induces inactivation of ALDH1 in a manner of mixed-type inhibition. Tertiary structural changes associated with regional hydrophobic exposure of the active site were observed. The urea binding regions on ALDH1 were predicted by docking simulations and were partly shared with active site residues of ALDH1 and with interface residues of the oligomerization domain for tetramer formation. The docking results suggest that urea prevents formation of the ALDH1 normal shape for the tetramer state as well as entrance of the substrate into the active site. Our study provides insight into the structural changes that accompany urea-mediated unfolding of ALDH1 and the catalytic role associated with conformational changes.

Zhaoxin Lu – 2nd expert on this subject based on the ideXlab platform

  • alleviating acute alcoholic liver injury in mice with bacillus subtilis co expressing alcohol Dehydrogenase and Acetaldehyde Dehydrogenase
    Journal of Functional Foods, 2018
    Co-Authors: Jing Lu, Fengxia Lu, Mingtong Li, Zhenghua Huang, Zhaoxin Lu

    Abstract:

    Abstract Alcohol consumption increases the risk of liver disease. Here, we investigated the effects of Bacillus subtilis co-expressing alcohol Dehydrogenase (ADH) and Acetaldehyde Dehydrogenase (ALDH), key enzymes in ethanol degradation, on acute alcohol-induced liver injury. Recombinant B. subtilis significantly alleviated alcohol-induced increase in the liver index, blood alcohol content, and serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activities. Furthermore, administration of ADH/ALDH-expressing B. subtilis inhibited lipid peroxidation and oxidative stress in the liver of alcohol-treated mice as evidenced by significant reduction of malondialdehyde and induction of total antioxidant capacity and glutathione and superoxide dismutase levels. Caecal microbiota diversity analysis indicated that administration of recombinant B. subtilis reversed alcohol-induced decrease in Firmicutes and increase in Proteobacteria, in particular pathogenic Helicobacter hepaticus, restoring the microbial composition in alcohol-treated mice. In conclusion, recombinant B. subtilis expressing ADH and ALDH could act as a novel candidate probiotic for prevention of alcohol-induced acute liver injury.

  • protective effects of lactococcus lactis expressing alcohol Dehydrogenase and Acetaldehyde Dehydrogenase on acute alcoholic liver injury in mice
    Journal of Chemical Technology & Biotechnology, 2018
    Co-Authors: Lei Zhong, Jing Lu, Fengxia Lu, Gisele Lapointe, Zhaoxin Lu

    Abstract:

    Background
    Alcohol Dehydrogenase (ADH) and Acetaldehyde Dehydrogenase (ALDH) play important roles in alcohol metabolism. Therefore, a possible effective way to attenuate the alcoholic liver damage is the exogenous supply of these two enzymes in stomach as they might accelerate the oxidation of ethanol into nontoxic acetate.

    Results
    ADH and ALDH were coexpressed in Lactococcus lactis NZ3900 and used as treatments towards acute alcoholic liver injury in mice. Intragastric ethanol administration was carried out at 5.6 g/kg body weight per day in mice for 15 consecutive days and different doses of recombinant ADH-ALDH L. lactis treatment were administrated together with ethanol. A high dose of L. lactis recombinant ADH-ALDH treatment (ADH activity of 2000 U/kg BW and ALDH activity of 1000 U/kg BW) reduced the serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels by 38.1%, 54.8% and 23.2%, respectively, in ethanol-treated mice. Moreover, it also helped maintaining serum lipid levels and liver oxidative stress parameters against ethanol. Histopathological examination of mice livers revealed that L. lactis recombinant ADH-ALDH at a high dose (ADH activity of 2000 U/kg BW and ALDH activity of 1000 U/kg BW) protected liver tissue from the damage induced by ethanol.

    Conclusion
    Results demonstrated that L. lactis with ADH and ALDH activity exhibited a dose-dependent protective effect on alcohol-induced liver damage in mice.

  • Acetaldehyde Detoxification Using Resting Cells of Recombinant Escherichia coli Overexpressing Acetaldehyde Dehydrogenase
    Applied Biochemistry and Biotechnology, 2013
    Co-Authors: Chong Zhang, Junfeng Zhao, Fengxia Lu, Zhaoxin Lu

    Abstract:

    Acetaldehyde Dehydrogenase (E.C. 1.2.1.10) plays a key role in the Acetaldehyde detoxification. The recombinant Escherichia coli cells producing Acetaldehyde Dehydrogenase (ist-ALDH) were applied as whole-cell biocatalysts for biodegradation of Acetaldehyde. Response surface methodology (RSM) was employed to enhance the production of recombinant ist-ALDH. Under the optimum culture conditions containing 20.68 h post-induction time, 126.75 mL medium volume and 3 % (v/v) inoculum level, the maximum ist-ALDH activity reached 496.65 ± 0.81 U/mL, resulting in 12.5-fold increment after optimization. Furthermore, the optimum temperature and pH for the catalytic activity of wet cells were 40 °C and pH 9.5, respectively. The biocatalytic activity was improved 80 % by permeabilizing the recombinant cells with 0.075 % (v/v) Triton X-100. When using 2 mmol/L NAD+ as coenzyme, the permeabilized cells could catalyze 98 % of Acetaldehyde within 15 min. The results indicated that the recombinant E. coli with high productivity of ist-ALDH might be highly efficient and easy-to-make biocatalysts for Acetaldehyde detoxification.

Junmo Yang – 3rd expert on this subject based on the ideXlab platform

  • functional study of Acetaldehyde Dehydrogenase 1 aldh1 in keratinocytes microarray integrating bioinformatics approaches
    Journal of Biomolecular Structure & Dynamics, 2020
    Co-Authors: Minwoo Park, Junmo Yang, Yongdoo Park, Guoying Qian

    Abstract:

    The function of Acetaldehyde Dehydrogenase 1 (ALDH1) has been gradually elucidated in several diseases, especially in various cancers. However, the role of ALDH1 in skin-related diseases has been m…

  • a computational integrating kinetic study on the flexible active site of human Acetaldehyde Dehydrogenase 1
    Process Biochemistry, 2016
    Co-Authors: Junmo Yang, Yingying Xu, Hee Seung Yang, Zhirong Lu, Hang Mu, Qian Zhang, Yongdoo Park

    Abstract:

    Abstract In order to gain more insight into the relation between the structure of Acetaldehyde Dehydrogenase 1 (ALDH1) and its catalytic and regional active site properties, the denaturant guanidine hydrochloride (GdnHCl) was employed in this study. The effects of GdnHCl on ALDH1 conformational and functional changes were evaluated by kinetic analysis and by performing computational molecular dynamics (MD) simulations. We found that direct binding of GdnHCl to ALDH1 induced complete inactivation prior to conspicuous changes in its tertiary structure or hydrophobic exposure, indicating that the active site is flexible compared to the overall structure. Kinetic experimental results and computational simulations indicated that there are specific sites on ALDH1 to which guanidine binds, resulting in blocking of catalytic function without a large degree of structural disruption. These sites may lay specifically in a cofactor-binding region, which was suggested by the observation of mixed-type inhibition. Our study provides insight into the flexibility of the ALDH1 active site through the use of GdnHCl denaturant and computational simulations to suggest possible binding mechanisms of inhibitors for the clinical applications.

  • integration of inhibition kinetics and molecular dynamics simulations to determine the effects of zn2 on Acetaldehyde Dehydrogenase 1
    Process Biochemistry, 2015
    Co-Authors: Yingying Xu, Yongdoo Park, Zhirong Lu, Qian Zhang, Jing Jing Wang, Xi Xi Wang, Haimeng Zhou, Junmo Yang

    Abstract:

    Abstract Understanding the mechanism of inhibition of Acetaldehyde Dehydrogenase 1 (ALDH1) is clinically important because this enzyme is involved in several types of cancers and other diseases. In this study, we investigated the effects of Zn2+ on the structure of ALDH1 by integrating kinetic inhibition studies with computational simulations. Tertiary structure and hydrophobic surface changes were also assessed by measuring intrinsic and ANS-binding fluorescence. The crystallographic structure of ALDH1 was applied in computational docking as well as molecular dynamics simulations. We found that the direct binding of Zn2+ to ALDH1 induces structural changes and inhibits ALDH1 activity. Moreover, Zn2+-mediated inactivation of ALDH1 was associated with structural changes. Specifically, beta regions of ALDH1 were exposed upon binding of Zn2+ and underwent significant conformational changes, including the loss of beta secondary structure. Our study provides insight into the structural changes that accompany Zn2+-mediated inhibition of ALDH1. Our findings also suggest that Zn2+, a potent inhibitor of ALDH1, may be useful in the treatment of ALDH1-related diseases.