Acetaldehyde Dehydrogenase

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Yongdoo Park - One of the best experts 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.

  • 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.

  • detection of down regulated Acetaldehyde Dehydrogenase 1 in atopic dermatitis patients by two dimensional electrophoresis
    Experimental Dermatology, 2007
    Co-Authors: Junmo Yang, Yongdoo Park, Youjeong Lyou
    Abstract:

    :  We conducted the proteomic studies to detect the dysregulated proteins in the atopic dermatitis (AD) proteome obtained from the patient-derived primary cultured fibroblasts. Acetaldehyde Dehydrogenase 1 (ALDH1) was detected as being significantly down-regulated at the pH ranges of 6–9 and 4–7. The transcriptional levels of ALDH1, as detected by RT-PCR and real-time PCR, further confirmed the down-regulated phenomena for all the AD-fibroblasts (n = 20). The expression levels of ALDH1 in the whole skin tissue samples were further supported by the results of the primary cultured samples. These findings clearly demonstrate that ALDH1 can be a dermal biomarker for AD disease.

Zhaoxin Lu - One of the best experts 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, Fengxia Lu, Jing 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.

  • gene cloning expression and characterization of a novel Acetaldehyde Dehydrogenase from issatchenkia terricola strain xj 2
    Applied Microbiology and Biotechnology, 2012
    Co-Authors: Chong Zhang, Fengxia Lu, Zhaoxin Lu
    Abstract:

    Acetaldehyde is a known mutagen and carcinogen. Active aldehyde Dehydrogenase (ALDH) represents an important mechanism for Acetaldehyde detoxification. A yeast strain XJ-2 isolated from grape samples was found to produce Acetaldehyde Dehydrogenase with a high activity of 2.28 U/mg and identified as Issatchenkia terricola. The enzyme activity was validated by oxidizing Acetaldehyde to acetate with NAD+ as coenzyme based on the headspace gas chromatography analysis. A novel Acetaldehyde Dehydrogenase gene (ist-ALD) was cloned by combining SiteFinding-PCR and self-formed adaptor PCR. The ist-ALD gene comprised an open reading frame of 1,578 bp and encoded a protein of 525 amino acids. The predicted protein of ist-ALD showed the highest identity (73%) to ALDH from Pichia angusta. The ist-ALD gene was expressed in Escherichia coli, and the gene product (ist-ALDH) presented a productivity of 442.3 U/mL cells. The purified ist-ALDH was a homotetramer of 232 kDa consisting of 57 kDa-subunit according to the SDS-PAGE and native PAGE analysis. Ist-ALDH exhibited the optimal activity at pH 9.0 and 40°C, respectively. The activity of ist-ALDH was enhanced by K+, NH4+, dithiothreitol, and 2-mercaptoethanol but strongly inhibited by Ag+, Hg2+, Cu2+, and phenylmethyl sulfonylfluoride. In the presence of NAD+, ist-ALDH could oxidize many aliphatic, aromatic, and heterocyclic aldehydes, preferably Acetaldehyde. Kinetic study revealed that ist-ALDH had a kcat value of 27.71/s and a kcat/Km value of 26.80 × 103/(mol s) on Acetaldehyde, demonstrating ist-ALDH, a catalytically active enzyme by comparing with other ALDHs. These studies indicated that ist-ALDH was a potential enzymatic product for Acetaldehyde detoxification.

Junmo Yang - One of the best experts 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.

  • detection of down regulated Acetaldehyde Dehydrogenase 1 in atopic dermatitis patients by two dimensional electrophoresis
    Experimental Dermatology, 2007
    Co-Authors: Junmo Yang, Yongdoo Park, Youjeong Lyou
    Abstract:

    :  We conducted the proteomic studies to detect the dysregulated proteins in the atopic dermatitis (AD) proteome obtained from the patient-derived primary cultured fibroblasts. Acetaldehyde Dehydrogenase 1 (ALDH1) was detected as being significantly down-regulated at the pH ranges of 6–9 and 4–7. The transcriptional levels of ALDH1, as detected by RT-PCR and real-time PCR, further confirmed the down-regulated phenomena for all the AD-fibroblasts (n = 20). The expression levels of ALDH1 in the whole skin tissue samples were further supported by the results of the primary cultured samples. These findings clearly demonstrate that ALDH1 can be a dermal biomarker for AD disease.

Victor R Preedy - One of the best experts on this subject based on the ideXlab platform.

  • generation of protein adducts with malondialdehyde and Acetaldehyde in muscles with predominantly type i or type ii fibers in rats exposed to ethanol and the Acetaldehyde Dehydrogenase inhibitor cyanamide
    The American Journal of Clinical Nutrition, 2002
    Co-Authors: Onni Niemela, Seppo Parkkila, Michael Koll, Victor R Preedy
    Abstract:

    Background: Alcoholic myopathy is known to primarily affect type II muscle fibers (glycolytic, fast-twitch, anaerobic), whereas type I fibers (oxidative, slow-twitch, aerobic) are relatively protected. Objective: We investigated whether aldehyde-derived adducts of proteins with malondialdehyde and Acetaldehyde are formed in muscle of rats as a result of acute exposure to ethanol and Acetaldehyde. The differences between type I muscle, type II muscle, and liver tissue were also assessed. Design: The formation and distribution of malondialdehyde- and Acetaldehyde-protein adducts were studied with immunohistochemistry in soleus (type I) muscle, plantaris (type II) muscle, and liver in 4 groups of rats. The different groups were administered saline (control), cyanamide (an Acetaldehyde Dehydrogenase inhibitor), ethanol, and cyanamide + ethanol. Results: Treatment of rats with ethanol and cyanamide + ethanol increased the amount of aldehyde-derived protein adducts in both soleus and plantaris muscle. The greatest responses in malondialdehyde-protein and Acetaldehyde-protein adducts were observed in plantaris muscle, in which the effect of alcohol was further potentiated by cyanamide pretreatment. Malondialdehyde- and Acetaldehyde-protein adducts were also found in liver specimens from rats treated with ethanol and ethanol + cyanamide; the most abundant amounts were found in rats given cyanamide pretreatment. Conclusions: Acute ethanol administration increases protein adducts with malondialdehyde and Acetaldehyde, primarily in type II muscle. This may be associated with the increased susceptibility of anaerobic muscle to alcohol toxicity. Higher Acetaldehyde concentrations exacerbate adduct formation, especially in type II‐predominant muscles. The present findings are relevant to studies on the pathogenesis of alcohol-induced myopathy. Am J Clin Nutr 2002;76:668‐74.

Yingying Xu - One of the best experts on this subject based on the ideXlab platform.

  • 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.

  • 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.