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International Journal of Biological... Apr 2024Although Alzheimer's disease (AD) characterized with senile plaques and neurofibrillary tangles has been found for over 100 years, its molecular mechanisms are... (Review)
Review
Although Alzheimer's disease (AD) characterized with senile plaques and neurofibrillary tangles has been found for over 100 years, its molecular mechanisms are ambiguous. More worsely, the developed medicines targeting amyloid-beta (Aβ) and/or tau hyperphosphorylation did not approach the clinical expectations in patients with moderate or severe AD until now. This review unveils the role of a vicious cycle between Aβ-derived formaldehyde (FA) and FA-induced Aβ aggregation in the onset course of AD. Document evidence has shown that Aβ can bind with alcohol dehydrogenase (ADH) to form the complex of Aβ/ADH (ABAD) and result in the generation of reactive oxygen species (ROS) and aldehydes including malondialdehyde, hydroxynonenal and FA; in turn, ROS-derived HO and FA promotes Aβ self-aggregation; subsequently, this vicious cycle accelerates neuron death and AD occurrence. Especially, FA can directly induce neuron death by stimulating ROS generation and tau hyper hyperphosphorylation, and impair memory by inhibiting NMDA-receptor. Recently, some new therapeutical methods including inhibition of ABAD activity by small molecules/synthetic polypeptides, degradation of FA by phototherapy or FA scavengers, have been developed and achieved positive effects in AD transgenic models. Thus, breaking the vicious loop may be promising interventions for halting AD progression.
Topics: Humans; Alzheimer Disease; Alcohol Dehydrogenase; Reactive Oxygen Species; Hydrogen Peroxide; Amyloid beta-Peptides; Formaldehyde
PubMed: 38432266
DOI: 10.1016/j.ijbiomac.2024.130580 -
International Journal of Molecular... Oct 2022The effect of the interaction between fullerenol C(OH) (FUL) and alcohol dehydrogenase (ADH) from and human serum albumin (HSA) was studied by absorption spectroscopy,...
The effect of the interaction between fullerenol C(OH) (FUL) and alcohol dehydrogenase (ADH) from and human serum albumin (HSA) was studied by absorption spectroscopy, fluorescence spectroscopy, and time-resolved fluorescence spectroscopy. As shown in the study, the fluorescence intensities of ADH and HSA at excitation wavelengths λ = 280 nm (Trp, Tyr) and λ = 295 nm (Trp) are decreased with the increase in the FUL concentration. The results of time-resolved measurements indicate that both quenching mechanisms, dynamic and static, are present. The binding constant K and the number of binding sites were obtained for HSA and ADH. Thus, the results indicated the formation of FUL complexes and proteins. However, the binding of FUL to HSA is much stronger than that of ADH. The transfer of energy from the protein to FUL was also proved.
Topics: Humans; Serum Albumin; Alcohol Dehydrogenase; Binding Sites; Spectrometry, Fluorescence; Serum Albumin, Human; Nanoparticles; Protein Binding; Thermodynamics; Circular Dichroism
PubMed: 36293241
DOI: 10.3390/ijms232012382 -
Biochemistry Sep 2014Yeast (Saccharomyces cerevisiae) alcohol dehydrogenase I (ADH1) is the constitutive enzyme that reduces acetaldehyde to ethanol during the fermentation of glucose. ADH1...
Yeast (Saccharomyces cerevisiae) alcohol dehydrogenase I (ADH1) is the constitutive enzyme that reduces acetaldehyde to ethanol during the fermentation of glucose. ADH1 is a homotetramer of subunits with 347 amino acid residues. A structure for ADH1 was determined by X-ray crystallography at 2.4 Å resolution. The asymmetric unit contains four different subunits, arranged as similar dimers named AB and CD. The unit cell contains two different tetramers made up of "back-to-back" dimers, AB:AB and CD:CD. The A and C subunits in each dimer are structurally similar, with a closed conformation, bound coenzyme, and the oxygen of 2,2,2-trifluoroethanol ligated to the catalytic zinc in the classical tetrahedral coordination with Cys-43, Cys-153, and His-66. In contrast, the B and D subunits have an open conformation with no bound coenzyme, and the catalytic zinc has an alternative, inverted coordination with Cys-43, Cys-153, His-66, and the carboxylate of Glu-67. The asymmetry in the dimeric subunits of the tetramer provides two structures that appear to be relevant for the catalytic mechanism. The alternative coordination of the zinc may represent an intermediate in the mechanism of displacement of the zinc-bound water with alcohol or aldehyde substrates. Substitution of Glu-67 with Gln-67 decreases the catalytic efficiency by 100-fold. Previous studies of structural modeling, evolutionary relationships, substrate specificity, chemical modification, and site-directed mutagenesis are interpreted more fully with the three-dimensional structure.
Topics: Alcohol Dehydrogenase; Biocatalysis; Catalytic Domain; Crystallography, X-Ray; Models, Molecular; Protein Conformation; Saccharomyces cerevisiae
PubMed: 25157460
DOI: 10.1021/bi5006442 -
Medicina (Kaunas, Lithuania) Dec 2021: The aim of the current study was to assess the use of determinations of total alcohol dehydrogenase and the activity of its isoenzymes as well as aldehyde...
: The aim of the current study was to assess the use of determinations of total alcohol dehydrogenase and the activity of its isoenzymes as well as aldehyde dehydrogenase in the serum of patients with alcohol liver disease. : The testing was performed on the serum of 38 patients with alcoholic fatty liver (26 males and 12 females aged 31-75). The total activity of ADH was determined by the colorimetric method. The activity of ADH I and ADH II, as well as ALDH, was determined by the spectrofluorometric method using fluorogenic specific substrates. The activity of isoenzymes of other classes was determined by spectrophotometric methods using substrates. : A statistically significantly higher ADH I activity was noted in the serum of patients with alcoholic fatty liver (4.45 mIU/L) compared to the control group (2.04 mIU/L). A statistically significant increase in the activity was also noted for the class II alcohol dehydrogenase isoenzyme (29.21 mIU/L, control group: 15.56 mIU/L) and the total ADH (1.41 IU/L, control group: 0.63 IU/L). : The obtained results imply the diagnostic usefulness of the determination of AHD total, ADH I, and ADH II activity in the serum of patients with alcoholic fatty liver.
Topics: Adult; Aged; Alcohol Dehydrogenase; Aldehyde Dehydrogenase; Fatty Liver, Alcoholic; Female; Humans; Isoenzymes; Male; Middle Aged
PubMed: 35056333
DOI: 10.3390/medicina58010025 -
Scientific Reports Feb 2020Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) encode essential alcohol-metabolizing enzymes. While alcohol use is associated with spontaneously deep... (Clinical Trial)
Clinical Trial
Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) encode essential alcohol-metabolizing enzymes. While alcohol use is associated with spontaneously deep intracerebral haemorrhage (SDICH), particularly in males, the activities and genetic variants of ADH and ALDH may affect SDICH development. This case-control study was conducted to identify the interaction of alcohol use and SDICH with five single-nucleotide polymorphisms (SNPs): ADH1B rs1229984, ADH1C rs2241894, ALDH2 rs671, ALDH2 rs886205, and ALDH2 rs4648328. We enrolled 208 patients with SDICH and 244 healthy controls in a Taiwanese population. ALDH2 rs671 was significantly associated with SDICH in the dominant (P < 0.001) and additive models (P = 0.007). ALDH2 rs4648328 was borderline significantly associated with SDICH in the recessive (P = 0.024) or additive models (P = 0.030). In alcohol-using patients, the ALDH2 rs671 GG genotype was associated with SDICH risk compared to the GA+AA genotype (P = 0.010). ADH1B rs1229984, ADH1C rs2241894, and ALDH2 rs886205 did not demonstrate association with SDICH. Thus, the ALDH2 rs671 GG genotype is a risk factor for SDICH. Because the genetic distributions of ALDH2 rs671 exhibited strong ethnic heterogeneity, further studies in different populations are needed to validate these findings.
Topics: Aged; Alcohol Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; Asian People; Cerebral Hemorrhage; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Retrospective Studies; Risk Factors; Taiwan
PubMed: 32107439
DOI: 10.1038/s41598-020-60567-5 -
Poultry Science May 2022Ethanol is one of the most widely used and abused drugs. Following ethanol consumption, ethanol enters the bloodstream from the small intestine where it gets distributed...
Ethanol is one of the most widely used and abused drugs. Following ethanol consumption, ethanol enters the bloodstream from the small intestine where it gets distributed to peripheral tissues. In the bloodstream, ethanol is cleared from the system by the liver. The primary metabolism of ethanol uses alcohol dehydrogenase (ADH). In mammals, females appear to have higher ADH activity in liver samples than males. The purpose of the first experiment was to analyze sex differences in ADH levels following 12 d of ethanol administration (i.e., water or 2 g/kg) in male and female quail. Following the last daily treatment of ethanol, quail were euthanized, their livers were extracted, and ADH was analyzed in liver homogenate samples. Results showed that female quail had higher ADH levels, heavier livers, and a greater liver to body weight ratio than male quail. In a second experiment, we aimed to develop a blood ethanol concentration (BEC) profile for both male and female quail. Quail were administered 0.75 or 2 g/kg of ethanol and blood was collected at 0.5, 1, 2, 4, 6, 8, 12, 24 h after gavage administration. Blood ethanol concentration was analyzed using an Analox. We found that quail had a fairly rapid increase in BECs followed by a steady and slow disappearance of ethanol from the blood samples. Female quail had a lower peak of ethanol concentration and a smaller area under the curve (AUC) than male quail. The current research suggests that higher ADH levels in female quail may be responsible for increased metabolism of ethanol. In general, quail appear to eliminate ethanol more slowly than rodents. Thus, as a model, they may allow for a prolonged window with which to investigate the effects of ethanol.
Topics: Alcohol Dehydrogenase; Animals; Blood Alcohol Content; Chickens; Coturnix; Ethanol; Female; Liver; Male; Mammals; Sex Characteristics
PubMed: 35316649
DOI: 10.1016/j.psj.2022.101790 -
International Journal of Molecular... May 2023Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10), a homo-tetrameric multifunctional protein with 1044 residues encoded by the gene, is necessary for brain... (Review)
Review
Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10), a homo-tetrameric multifunctional protein with 1044 residues encoded by the gene, is necessary for brain cognitive function. Missense mutations result in infantile neurodegeneration, an inborn error in isoleucine metabolism. A 5-methylcytosine hotspot underlying a 388-T transition leads to the HSD10 (p.R130C) mutant to be responsible for approximately half of all cases suffering with this mitochondrial disease. Fewer females suffer with this disease due to X-inactivation. The binding capability of this dehydrogenase to Aβ-peptide may play a role in Alzheimer's disease, but it appears unrelated to infantile neurodegeneration. Research on this enzyme was complicated by reports of a purported Aβ-peptide-binding alcohol dehydrogenase (ABAD), formerly referred to as endoplasmic-reticulum-associated Aβ-binding protein (ERAB). Reports concerning both ABAD and ERAB in the literature reflect features inconsistent with the known functions of 17β-HSD10. It is clarified here that ERAB is reportedly a longer subunit of 17β-HSD10 (262 residues). 17β-HSD10 exhibits L-3-hydroxyacyl-CoA dehydrogenase activity and is thus also referred to in the literature as short-chain 3-hydorxyacyl-CoA dehydrogenase or type II 3-hydorxyacyl-CoA dehydrogenase. However, 17β-HSD10 is not involved in ketone body metabolism, as reported in the literature for ABAD. Reports in the literature referring to ABAD (i.e., 17β-HSD10) as a alcohol dehydrogenase, relying on data underlying ABAD's activities, were found to be unreproducible. Furthermore, the rediscovery of ABAD/ERAB's mitochondrial localization did not cite any published research on 17β-HSD10. Clarification of the purported ABAD/ERAB function derived from these reports on ABAD/ERAB may invigorate this research field and encourage new approaches to the understanding and treatment of -gene-related disorders. We establish here that infantile neurodegeneration is caused by mutants of 17β-HSD10 but not ABAD, and so we conclude that ABAD represents a misnomer employed in high-impact journals.
Topics: Humans; Alcohol Dehydrogenase; Alzheimer Disease; Mutation, Missense; 3-Hydroxyacyl CoA Dehydrogenases
PubMed: 37239833
DOI: 10.3390/ijms24108487 -
Biomolecules Apr 2016Alcohol consumption causes damage to various organs and systems.[...].
Alcohol consumption causes damage to various organs and systems.[...].
Topics: Alcohol Dehydrogenase; Cytochrome P-450 CYP2E1; Ethanol; Humans; Liver; Oxidative Stress
PubMed: 27092531
DOI: 10.3390/biom6020020 -
Applied and Environmental Microbiology Jun 2023sp. strain SYK-6 is an efficient aromatic catabolic bacterium that can consume all four stereoisomers of 1,2-diguaiacylpropane-1,3-diol (DGPD), which is a ring-opened...
sp. strain SYK-6 is an efficient aromatic catabolic bacterium that can consume all four stereoisomers of 1,2-diguaiacylpropane-1,3-diol (DGPD), which is a ring-opened β-1-type dimer. Recently, LdpA-mediated catabolism of -DGPD was reported in SYK-6, but the catabolic pathway for -DGPD was as yet unknown. Here, we elucidated the catabolism of -DGPD, which proceeds through conversion to -DGPD. When -DGPD was incubated with SYK-6, the Cα hydroxy groups of -DGPD (DGPD I and II) were initially oxidized to produce the Cα carbonyl form (DGPD-keto I and II). This initial oxidation step is catalyzed by Cα-dehydrogenases, which belong to the short-chain dehydrogenase/reductase (SDR) family and are involved in the catabolism of β-O-4-type dimers. Analysis of seven candidate genes revealed that NAD-dependent LigD and LigL are mainly involved in the conversion of DGPD I and II, respectively. Next, we found that DGPD-keto I and II were reduced to -DGPD (DGPD III and IV) in the presence of NADPH. Genes involved in this reduction were sought from Cα-dehydrogenase and -neighboring SDR genes. The gene products of SLG_12690 () and SLG_12640 () catalyzed the NADPH-dependent conversion of DGPD-keto I to DGPD III and DGPD-keto II to DGPD IV, respectively. Mutational analysis further indicated that and are predominantly involved in the reduction of DGPD-keto. Together, these results demonstrate that SYK-6 harbors a comprehensive catabolic enzyme system to utilize all four β-1-type stereoisomers through successive oxidation and reduction reactions of the Cα hydroxy group of -DGPD with a net stereoinversion using multiple dehydrogenases. In many catalytic depolymerization processes of lignin polymers, aryl-ether bonds are selectively cleaved, leaving carbon-carbon bonds between aromatic units intact, including dimers and oligomers with β-1 linkages. Therefore, elucidating the catabolic system of β-1-type lignin-derived compounds will aid in the establishment of biological funneling of heterologous lignin-derived aromatic compounds to value-added products. Here, we found that -DGPD was converted by successive stereoselective oxidation and reduction at the Cα position by multiple alcohol dehydrogenases to -DGPD, which is further catabolized. This system is very similar to that developed to obtain enantiopure alcohols from racemic alcohols by artificially combining two enantiocomplementary alcohol dehydrogenases. The results presented here demonstrate that SYK-6 has evolved to catabolize all four stereoisomers of DGPD by incorporating this stereoinversion system into its native β-1-type dimer catabolic system.
Topics: Lignin; NADP; Alcohol Dehydrogenase; Oxidation-Reduction; Alcohols
PubMed: 37184397
DOI: 10.1128/aem.00171-23 -
Angewandte Chemie (International Ed. in... Mar 2021Controlling the selectivity of a chemical reaction with external stimuli is common in thermal processes, but rare in visible-light photocatalysis. Here we show that the...
Controlling the selectivity of a chemical reaction with external stimuli is common in thermal processes, but rare in visible-light photocatalysis. Here we show that the redox potential of a carbon nitride photocatalyst (CN-OA-m) can be tuned by changing the irradiation wavelength to generate electron holes with different oxidation potentials. This tuning was the key to realizing photo-chemo-enzymatic cascades that give either the (S)- or the (R)-enantiomer of phenylethanol. In combination with an unspecific peroxygenase from Agrocybe aegerita, green light irradiation of CN-OA-m led to the enantioselective hydroxylation of ethylbenzene to (R)-1-phenylethanol (99 % ee). In contrast, blue light irradiation triggered the photocatalytic oxidation of ethylbenzene to acetophenone, which in turn was enantioselectively reduced with an alcohol dehydrogenase from Rhodococcus ruber to form (S)-1-phenylethanol (93 % ee).
Topics: Acetophenones; Agrocybe; Alcohol Dehydrogenase; Benzene Derivatives; Catalysis; Light; Mixed Function Oxygenases; Molecular Structure; Nitriles; Oxidation-Reduction; Phenylethyl Alcohol; Photochemical Processes; Rhodococcus; Stereoisomerism
PubMed: 33529432
DOI: 10.1002/anie.202100164