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81.
Aldehyde oxidase is a member of the molybd-flavo enzyme family that catalyzes the hydroxylation of heterocycles and the oxidation of aldehydes into corresponding carboxylic acids. Aldehyde oxidase-1 (AOX1) is highly expressed in liver and is involved in the oxidation of a variety of aldehydes and nitrogenous heterocyclic compounds, including anti-cancer and immunosuppressive drugs. However, the physiological substrates of AOX1 have not been identified, and it was unknown how the expression of AOX1 is regulated. Here, we found that the AOX1 gene is regulated by the Nrf2 pathway. Two Nrf2 binding consensus elements (antioxidant responsive element, ARE) are located in the 5' upstream region of the rat AOX1 gene. Molecular analyses using reporter transfection analysis, EMSA, and ChIP analysis show that Nrf2 binds to and strongly activates the rat AOX1 gene. 相似文献
82.
Aldehyde dehydrogenases (ALDHs) are members of NAD(P)(+)-dependent protein superfamily that catalyze the oxidation of a wide range of endogenous and exogenous highly reactive aliphatic and aromatic aldehyde molecules to their corresponding non toxic carboxylic acids. Research evidence has shown that ALDHs represent a promising class of genes to improve growth development, seed storage and environmental stress adaptation in higher plants. The recently completed genome sequences of several plant species have resulted in the identification of a large number of ALDH genes, most of which still need to be functionally characterized. In this paper, we identify members of the ALDH gene superfamily in soybean genome, and provide a unified nomenclature for the entire soybean ALDH gene families. The soybean genome contains 18 unique ALDH sequences encoding members of five ALDH families involved in a wide range of metabolic and molecular detoxification pathways. In addition, we describe the biochemical requirements and cellular metabolic pathways of selected members of ALDHs in soybean responses to environmental stress conditions. 相似文献
83.
Benzoylformate decarboxylase (BFD) enhances the rate of decarboxylation of its key intermediate compared to the nonenzymic reaction by a factor of about 106. It has been proposed that desolvation into a hydrophobic environment will lower the reaction barrier in TDP-dependent decarboxylases. The competition of thiamin thiazolone diphosphate (TTDP) with the cofactor thiamin diphosphate (TDP) provides a dynamic indication of the relative hydrophobicity of the cofactor binding site. BFD binds the more polar TDP tightly in the presence of excess TTDP. Therefore, desolvation would not be likely to occur during catalysis. Unlike TDP enzymes that have electron acceptors as substrates, decarboxylases require protonation to produce the precursor to the aldehyde product. A mechanism involving an associated acid that traps the carbanion generated upon C–C bond breaking will permit diffusional separation of carbon dioxide and generate the appropriate precursor to the product aldehdye. This would also account for avoidance of a competitive reaction. Hasson’s detailed structure of BFD shows a highly polar active site with histidines in the vicinity of the substrate. Reports of a reduction of kcat to near the nonenzymic rate without a large effect on Km upon specific replacement of these histidines with alanine fit this alternative. In TDP enzymes involving oxidation or condensation, an electrophilic substrate or second cofactor will be bound (and no proton will be required). This will acquire the electron density of the carbanion itself. In such cases, protonated side chains are not functional while hydrophobic environments would promote the internal transfer. 相似文献
84.
目的探讨乙醛脱氢酶1(ALDH1)蛋白表达与胶质瘤干细胞体外分化相关性。
方法将原代培养的胶质瘤干细胞分为分化组与对照组,分化组细胞使用10%的胎牛血清诱导,对照组细胞继续在无血清环境中培养,通过免疫荧光细胞化学染色和Western blot观察两组细胞ALDH1蛋白的表达情况,分别使用Wilcoxon符号秩检验和配对样本t检验分析两组ALDH1阳性细胞率和相对蛋白含量的差异。
结果分化组细胞呈完全贴壁生长,异型性明显,对照组细胞呈团状聚集,形态较为均一。两组的ALDH1阳性细胞率分别为:分化组18.78%?±?6.03%,对照组81.23%±?3.19%;ALDH1相对蛋白含量分别为:分化组0.035±0.009,对照组0.390±0.108。两组的阳性细胞率和相对蛋白含量比较差异具有统计学意义(Z = -2.666,P = 0.008;t = -10.637,P = 0.000)。
结论本实验通过半定量研究进一步证实了在体外培养状态下,ALDH1主要存在于较为原始的肿瘤细胞中,分化后几乎不表达,提示ALDH1作为可能的胶质瘤干细胞标志物仍有进一步研究的价值。 相似文献
85.
Sorouraddin MH Fooladi E Naseri A Rashidi MR 《Journal of biochemical and biophysical methods》2008,70(6):999-1005
Although phenanthridine has been frequently used as a specific substrate for the assessment of aldehyde oxidase activity, the use of this method is questionable due to a lower limit of detection and its validity for kinetic studies. In the present study, a novel sensitive multivariate calibration method based on partial least squares (PLS) has been developed for the measurement of aldehyde oxidase activity using phenanthridine as a substrate. Phenanthridine and phenanthridinone binary mixtures were prepared in a dynamic linear range of 0.1–30.0 μM and the absorption spectra of the solutions were recorded in the range of 210–280 nm in Sorenson's phosphate buffer (pH 7.0) containing EDTA (0.1 mM). The optimized PLS calibration model was used to calculate the concentration of each chemical in the prediction set. Hepatic rat aldehyde oxidase was partially purified and the initial oxidation rates of different concentrations of phenanthridine were calculated using the PLS method. The values were used for calculating Michaelis–Menten constants from a Lineweaver–Burk double reciprocal plot of initial velocity against the substrate concentration. The limits of detection for phenanthridine and phenanthridinone were found to be 0.04 ± 0.01 and 0.03 ± 0.01 μM (mean ± SD, n = 5), respectively. Using this method, the Km value for the oxidation of phenanthridine was calculated as 1.72 ± 0.09 μM (mean ± SD, n = 3). Thus, this study describes a novel spectrophotometric method that provides a suitable, sensitive and easily applicable means of measuring the kinetics of phenanthridine oxidation by aldehyde oxidase without the need for expensive instrumentation. 相似文献
86.
Daniel G. Silva Jean F.R. Ribeiro Daniela De Vita Lorenzo Cianni Caio Haddad Franco Lucio H. Freitas-Junior Carolina Borsoi Moraes Josmar R. Rocha Antonio C.B. Burtoloso Peter W. Kenny Andrei Leitão Carlos A. Montanari 《Bioorganic & medicinal chemistry letters》2017,27(22):5031-5035
The effects on potency of cruzain inhibition of replacing a nitrile group with alternative warheads were explored. The oxime was almost an order of magnitude more potent than the corresponding nitrile and has the potential to provide access to the prime side of the catalytic site. Dipeptide aldehydes and azadipeptide nitriles were found to be two orders of magnitude more potent cruzain inhibitors than the corresponding dipeptide nitriles although potency differences were modulated by substitution at P1 and P3. Replacement of the α methylene of a dipeptide aldehyde with cyclopropane led to a loss of potency of almost three orders of magnitude. The vinyl esters and amides that were characterized as reversible inhibitors were less potent than the corresponding nitrile by between one and two orders of magnitude. 相似文献
87.
Sang-Joon Lee Han-Young Kang Younghoon Lee 《Journal of Molecular Catalysis .B, Enzymatic》2003,26(3-6):265
More and more, aldolases are being recognized as useful catalysts that carry out the reversible addition of a ketone donor to an aldehyde acceptor in achieving high stereoselectivity. Threonine aldolases catalyze the synthesis of variable β-hydroxy-α-amino acids, which are important structural units of various antibiotics and immunosuppressants. However, the enzymatic properties need to be improved to support a broader application to synthetic chemistry. Although directed-evolution is a powerful tool for improving enzymatic properties, the successful outcome depends on the efficiency of screening systems. We designed and proposed two high-throughput screening schemes for selecting
-threonine aldolase mutants with improved properties. These schemes utilized the toxicity of aldehyde, which acts as an acceptor in the aldol condensation. In these schemes, the following occurs: (1) the higher
-threonine aldolase activity reduces the toxic effect of aldehyde, which leads to the survival of the corresponding clone (the positive-selection scheme), and (2) the higher
-threonine aldolase activity produces more toxic aldehyde, which causes the death of the corresponding clone (the negative-selection scheme). According to the positive-selection scheme, we successfully selected
-threonine aldolase mutants with higher activities than the wild-type, from a randomly generated LTA library. 相似文献
88.
Hiltrud White Claudia Huber Richard Feicht Helmut Simon 《Archives of microbiology》1993,159(3):244-249
Clostridium formicoaceticum grown in the presence of 1 mM molybdate and about 1.5×10-5 mM tungsten (present in the 5 g yeast extract/l of the growth medium) forms two reversible aldehyde oxidoreductases in an activity ratio of about 45:55. The fraction of 45% does not bind to the octyl-Sepharose column, whereas the 55% aldehyde oxidoreductase binds to this column. From cells grown on a synthetic medium without the addition of tungstate only about 2% of the aldehyde oxidoreductase of the crude extract binds to octyl-Sepharose. The enzyme not binding to octyl-Sepharose has been purified as judged by electrophoresis. It is pure after about 50 fold enrichment. According to SDS gel electrophoresis the enzyme consists of identical 100 kD subunits. Based on gel chromatography it seems to be a trimer. Per subunit 0.6 molybdenum, 7 iron, 6.6 acid labile sulphur, about 0.1 pterin-6-carboxylic and <0.05 tungsten have been found. The first 13 amino acids from the amino end show no similarity with the W-containing aldehyde oxidoreductase from the same bacterium. With reduced tetramethylviologen (E0=–550 mV) the new molybdenum containing enzyme can reduce various aliphatic and aromatic acids to aldehydes. The pH optimum is at 6.0. For the dehydrogenation of butyraldehyde a rather broad pH region from pH 6 to 10 shows almost no variation of rate. From 15 different aldehydes acetaldehyde exhibits the highest rate. The Km value for butanal is 0.002 and for propionate 7.0 mM. Compared with the tungsten enzyme the molybdenum enzyme is only moderately oxygen-sensitive.Abbreviations AOR
aldehyde oxidoreductase
- BV
benzylviologen
- MV
methylviologen
- NH2CO-MV
1,1-carbamoylmethylviologen
- TMV
1,1,2,2-tetramethylviologen 相似文献
89.
Richard N. Schicho Lesley J. Snowden Swarnalatha Mukund Jae-Bum Park Michael W. W. Adams Robert M. Kelly 《Archives of microbiology》1993,159(4):380-385
Pyrococcus furiosus is a strictly anaerobic heterotroph that grows optimally around 100 °C. It can be cultured in an artificial seawater-based medium with either peptides or maltose as the carbon source. Significant stimulation of cell yields were observed when trace levels of tungsten (as tungstate) were added to an energy-limited chemostat culture of P. furiosus when maltose is present, but not when peptides were the sole carbon source. The addition of tungsten also led to dramatic increases in the specific activities within cell-free extracts of aldehyde ferredoxin oxidoreductase (AOR), which is a tungsten-iron-sulfur protein. Moreover, the addition of tungsten to cells growing in maltose/peptide medium dramatically reduced the specific activity of intracellular proteases, suggesting a preference for the utilization of maltose over peptides as the carbon and energy source in the presence of tungsten.Non-standard abbreviations EPPS
N-[2-Hydroxyethyl]-piperazine-N-[3-propane-sulfonic acid]
- VFA
volatile fatty acids
- LNA
1-Lys-p-nitroaniline
- MeOSAPTNA
MeO-Suc-Arg-Pro-Tyr-p-nitroaniline
- AOR
aldehyde ferredoxin oxidoreductase 相似文献
90.
Claudia Huber Haike Skopan Richard Feicht Hiltrud White Hilmut Simon 《Archives of microbiology》1995,164(2):110-118
The αβ subunits of the tungsten-containing reversible aldehyde oxidoreductase of Clostridium thermoaceticum were shown to contain a pterin cofactor in the form of a mononucleotide. The substrate specificity of the enzyme for aliphatic
and aromatic aldehydes and for carboxylates was broad. The K
m
values for ethanal, propanal and butanal were 0.010–0.006 mM, but the value for methanal was 1.6 mM. Benzaldehyde derivatives
with a hydroxy group in the 4-position showed millimolar K
m
values that were 2–3 orders of magnitude higher than those of other aromatic and aliphatic aldehydes. The ratio of k
cat
/K
m
for aldehydes and the corresponding acids is 104–105. For carboxylate reduction, 4-hydroxy benzoate again showed the highest K
m
value of all substrates tested. When the 4-hydroxy groups of the aldehyde and the acid were methylated, the K
m
values were decreased drastically. From the temperature dependence of carboxylate reduction at the expense of viologens,
activation energies that depended on the substrate and on the applied viologen were calculated. The pH optima of the carboxylate
reductions depended on the pK values of the acids and shifted to lower pH values with lower pK values of the acids. The ternary
complex α3β3γ of the aldehyde oxidoreductase was able to dehydrogenate aldehydes to acylates with NADP+. Surprisingly the reverse reaction was observed too, although at very low rates. When exposed to air, the aldehyde oxidoreductase
showed markedly enhanced lability in its reduced state compared to its oxidized state. With resting cells of C. thermoaceticum, many carboxylates were reduced at the expense of carbon monoxide to the corresponding alcohols.
Received: 18 January 1995 / Accepted: 5 April 1995 相似文献