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91.
Co-synthesis of Human δ-Aminolevulinate Dehydratase (ALAD) Mutants with the Wild-type Enzyme in Cell-free System—Critical Importance of Conformation on Enzyme Activity— 下载免费PDF全文
Properties of mutant δ-aminolevulinate dehydratase (ALAD) found in patients with ALAD porphyria were studied by enzymological and immunological analyses after the synthesis of enzyme complexes using a cell-free system. Enzyme activities of homozygous G133R, K59N/G133R, V153M, and E89K mutants were 11%, 22%, 67%, and 75% of the wild-type ALAD, respectively, whereas that of K59N, a normal variant, was 112%. Enzyme activities of L273R, C132R and F12L were undetectable. Co-synthesis of F12L, L273R, G133R, K59N/G133R, or C132R mutants with the wild-type at various ratios showed that ALAD activity was proportionally decreased in the amount of the wild-type in the complex. In contrast, co-synthesis of V153M, K59N, and E89K with the wild-type did not influence enzyme activity of the wild-type. Surface charge changes in K59N, E89K, C132R and G133R predicted by mutations were also confirmed by native polyacrylamide gel electrophoresis. A compound E89K and C132R complex showed ALAD activity similar to that was found in erythrocytes of the patient. These findings indicate that cell-free synthesis of ALAD proteins reflects enzymatic activities found in patients, and suggest that, in addition to the direct effect of mutations on the catalytic activity, conformational effects play an important role in determining enzyme activity. 相似文献
92.
目的 探讨碳酸镧联合左卡尼汀治疗维持性血液透析慢性肾功能衰竭的临床疗效。方法 选取2019年1月—2021年12月在沧州市中心医院进行治疗的88例维持性血液透析慢性肾功能衰竭患者为研究对象,根据住院号的奇偶分为对照组和治疗组,每组各44例。对照组静脉滴注左卡尼汀注射液,50 mg/kg同0.9%氯化钠注射液100 mL配伍,1次/d;治疗组在对照组治疗基础上口服碳酸镧咀嚼片,0.5 g/次,3次/d。两组均连续治疗3个月。观察两组的临床疗效,比较两组治疗前后相关量表评分、肾功能指标、骨代谢指标、细胞因子指标和血管钙化积分的变化情况。结果 治疗后,治疗组总有效率是93.18%,显著高于对照组的81.82%(P<0.05)。治疗后,两组生活质量综合评定问卷(GQOLI-74)评分、社会支持评定量表(SSRS)评分、慢性病患者生命质量测定量表体系(QLICD-CRF 2.0)评分均较治疗前显著升高,但急性生理与慢性健康(APACHEⅡ)评分、SAPSⅡ评分均显著降低(P<0.05),并以治疗组改善的更明显(P<0.05)。治疗后,两组患者血肌酐(Scr)、尿素氮(BUN)水平均较治疗前显著降低,但内生肌酐清除率(Ccr)水平均显著升高(P<0.05);治疗后,治疗组肾功能指标改善优于对照组(P<0.05)。治疗后,两组血钙(Ca)血磷(P)、全段甲状旁腺激素(iPTH)水平均较治疗前显著降低(P<0.05),并以治疗组改善更明显(P<0.05)。治疗后,两组血清基质金属蛋白酶-9(MMP-9)、胱抑素C(CysC)、基质细胞衍生因子-1(TSP-1)、β2-微球蛋白(β2-MG)、人成纤维细胞生长因子-23(FGF-23)均较同组治疗前显著降低,而骨形态发生蛋白-7(BMP-7)显著升高(P<0.05),并以治疗组改善更明显(P<0.05)。治疗后,两组患者冠状动脉钙化(CACS)积分、腹主动脉钙化(AACS)积分均显著降低(P<0.05),并以治疗组改善更明显(P<0.05)。结论 碳酸镧联合左卡尼汀治疗维持性血液透析慢性肾功能衰竭疗效明显,可有效改善患者肾功能和骨代谢指标,改善血清细胞因子水平,延缓血管钙化,有着良好的临床应用价值。 相似文献
93.
目的探讨补肾健骨胶囊联合唑来膦酸注射液和碳酸钙D3片治疗老年骨质疏松症的临床疗效。方法选择2012年5月—2015年1月在郫县人民医院骨科接受医治的114例骨质疏松症患者为研究对象,所有患者按照治疗方法的不同分为对照组和治疗组,每组各57例。所有患者均口服碳酸钙D3片,1片/次,1次/d。在此基础上对照组静脉滴注唑来膦酸注射液,5 mg加入生理盐水250 m L中,1次/月,每次滴注不少于15 min。治疗组在对照组基础上口服补肾健骨胶囊,4粒/次,3次/d。两组患者均连续治疗12个月。观察两组患者的临床疗效,比较骨代谢指标以及骨密度(BMD)、骨钙素(BGP)、骨形态发生蛋白(BMP-2)及视觉模拟(VAS)评分。结果治疗后,对照组和治疗组总有效率分别为82.46%、94.74%,两组总有效率比较差异有统计学意义(P0.05)。治疗后,两组血钙(S-Ca)、血磷(S-P)明显增高,碱性磷酸酶(ALP)显著降低,同组治疗前后差异具有统计学意义(P0.05);且治疗组这些观察指标的改善程度优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者L2-L4 BMD、股骨颈BMD、BGP、BMP-2均明显增加,VAS评分明显降低,同组治疗前后差异具有统计学意义(P0.05);且治疗组这些观察指标的改善程度优于对照组,两组比较差异有统计学意义(P0.05)。对照组、治疗组的不良反应发生率分别为7.02%、8.77%,两组不良反应发生率比较差异无统计学意义。结论补肾健骨胶囊联合唑来膦酸注射液和碳酸钙D3片治疗老年骨质疏松症具有较好的临床效果,可有效增加患者BMD,明显改善骨代谢,减少骨量流失,值得临床推广应用。 相似文献
94.
目的探究α-酮酸联合碳酸钙改善维持性血液透析患者钙磷代谢的临床疗效。方法选取2015年1月—2015年7月在崇州市人民医院进行维持性血液透析治疗的患者82例,随机分为对照组与治疗组,每组各41例。对照组患者口服碳酸钙D3片,600 mg/次,2次/d。治疗组在对照组基础上,餐中口服复方α-酮酸片,4片/次,3次/d。两组的治疗时间不低于6个月。分析两组患者治疗前、治疗后3、6个月血液中钙磷的量、钙磷乘积、血清中碱性磷酸酶(AKP)、甲状旁腺激素(PTH)水平、血白蛋白含量、综合性营养评估(SGA)及BMI指数的变化情况。结果治疗后3、6个月,两组患者的血磷量和钙磷乘积明显降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组的降低程度优于对照组(P0.05)。治疗后3、6个月,两组PTH值均降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组的PTH值显著低于同期对照组,两组比较差异具有统计学意义(P0.05)。治疗后3、6个月,两组血白蛋白量、SGA评分、BMI指数均得到改善,同组治疗前后差异具有统计学意义(P0.05);且治疗组这些观察指标显著优于同期对照组,两组比较差异具有统计学意义(P0.05)。结论复方α-酮酸联合碳酸钙能明显改善维持性血液透析患者的钙磷代谢情况,提高患者的营养状况,可有效的预防并发症发生。 相似文献
95.
Gabriela Bonfanti Ronise B. Ceolin Tiago Valcorte Karine S. De Bona Leidiane de Lucca Thissiane L. Gonçalves Maria Beatriz Moretto 《Clinical biochemistry》2011,(13):1105-1109
Objectives
To investigate the activity of δ-Aminolevulinate dehydratase (δ-ALA-D) and its possible relationship with oxidative status, lipid profile, body mass index (BMI) in type 2 diabetics (DM2) patients.Design and methods
δ-ALA-D activity and reactivation index, as well as markers of oxidative stress and biochemical and anthropometrics parameters were determined in DM2 patients (n = 63) and controls (n = 63).Results
There was a decreased δ-ALA-D activity and a higher reactivation index (p < 0.05) in DM2 patients besides an elevated level of oxidative stress. Disturbances on lipid profile were related to the enzymatic activity and BMI also was correlated with oxidative level in DM2 patients (p < 0.05).Conclusion
There is an association between oxidative stress, abnormalities on lipid profile, distribution of body fat and δ-ALA-D activity inhibition as well as the enzyme is more oxidized in the DM2 suggesting that it would be a good biomarker for assessing prejudice in chronic metabolic processes. 相似文献96.
Reckziegel P Dias VT Benvegnú D Boufleur N Silva Barcelos RC Segat HJ Pase CS Dos Santos CM Flores EM Bürger ME 《Toxicology letters》2011,203(1):74-81
We investigated the antioxidant potential of gallic acid (GA), a natural compound found in vegetal sources, on the motor and oxidative damages induced by lead. Rats exposed to lead (50 mg/kg, i.p., once a day, 5 days) were treated with GA (13.5 mg/kg, p.o.) or EDTA (110 mg/kg, i.p.) daily, for 3 days. Lead exposure decreased the locomotor and exploratory activities, reduced blood ALA-D activity, and increased brain catalase (CAT) activity without altering other antioxidant defenses. Brain oxidative stress (OS) estimated by lipid peroxidation (TBARS) and protein carbonyl were increased by lead. GA reversed the motor behavior parameters, the ALA-D activity, as well as the markers of OS changed by lead exposure. CAT activity remained high, possibly as a compensatory mechanism to eliminate hydroperoxides during lead poisoning. EDTA, a conventional chelating agent, was not beneficial on the lead-induced motor behavior and oxidative damages. Both GA (less) and EDTA (more) reduced the lead accumulation in brain tissue. Negative correlations were observed between the behavioral parameters and lipid peroxidation and the lead levels in brain tissue. In conclusion, GA may be an adjuvant in lead exposure, mainly by its antioxidant properties against the motor and oxidative damages resulting from such poisoning. 相似文献
97.
Barney E. Dwyer Mark A. Smith Sandy L. Richardson George Perry Xiongwei Zhu 《Neuroscience letters》2009
Heme is an essential cell metabolite, intracellular regulatory molecule, and protein prosthetic group. Given the known alterations in heme metabolism and redox metal distribution and the up-regulation of heme oxygenase enzyme in Alzheimer's disease (AD), we hypothesized that heme dyshomeostasis plays a key role in the pathogenesis. To begin testing this hypothesis, we used qRT-PCR to quantify the expression of aminolevulinate synthase (ALAS1) and porphobilinogen deaminase (PBGD), rate-limiting enzymes in the heme biosynthesis pathway. The relative expression of ALAS1 mRNA, the first and rate-limiting enzyme for heme biosynthesis under normal physiological conditions, was significantly (p < 0.05) reduced by nearly 90% in AD compared to control. Coordinately, the relative expression of PBGD mRNA, which encodes porphobilinogen deaminase, the third enzyme in the heme synthesis pathway and a secondary rate-limiting enzyme in heme biosynthesis, was also significantly (p < 0.02) reduced by nearly 60% in AD brain compared to control and significantly related to apolipoprotein E genotype (p < 0.005). In contrast, the relative expression of ALAD mRNA, which encodes aminolevulinate dehydratase, the second and a non-rate-limiting enzyme for heme biosynthesis, was unchanged between the two groups. Taken together, our results suggest regulation of cerebral heme biosynthesis is profoundly altered in AD and may contribute toward disease pathogenesis by affecting cell metabolism as well as iron homeostasis. 相似文献
98.
Summary A cDNA coding for human 5-aminolevulinate dehydratase was placed in a yeast expression vector under the control of the GAL10 promoter. The resulting multicopy plasmid was then used to transform a yeast mutant which contains a defective hem2 gene coding for 5-aminolevulinate dehydratase. Expression of the human cDNA was shown in four ways: (1) restoration of normal growth on glycerol/galactose as primary carbon source, (2) decrease in intracellular 5-aminolevulinic acid concentration, (3) restoration of cytochrome biosynthesis and (4) direct, in situ assay of 5-aminolevulinic acid dehydratase. Curing transformed cells of plasmid restored the hem2 mutant phenotype. This heterologous system could be used to produce large quantities of human 5-aminolevulinic acid dehydratase for physical and biochemical studies. 相似文献
99.
Summary The solubility properties of hydroxyapatite (HA) are compared with those of human dental enamel and dentin. The apatites used
in this study were equilibrated with dilute phosphoric acid solutions in CO2-containing atmospheres. The experimental results are interpreted in terms of solubility models which consider the biological
materials as either HA or carbonatoapatites. Both in the HA and the dental mineral systems, the results are consistent with
the precipitation of another carbonate-containing apatitic phase during equilibration. However, although the chemical behavior
of the HA systems is in very good agreement with predictions based on the solubility models, the results with the bioapatities
are not; this inconsistency is more marked for dentin than for enamel but in both cases the results clearly indicate the inadequacy
of assuming for these dental apatites the stoichiometry of HA. The models and the experimental results show that, in principle,
it is possible to define the two dental minerals in terms of respective solubility product constants, if independent information
is attained on the stoichiometry of these bioapatites. 相似文献
100.
Yoko Morita Tadashi Sakai Shunichi Araki Takaharu Araki Yoshiaki Masuyama 《International archives of occupational and environmental health》1997,70(3):195-198
Objective: The objective of this study was to evaluate the usefulness of nicotinamide adenine dinucleotide synthetase (NADS) activity
for the biological monitoring of lead exposure.
Methods: The subjects were 76 male lead workers and 13 normal volunteers (7 males and 6 females). NADS activity and blood lead concentration
(Pb-B) was determined in each subject. Delta-aminolevulinic acid dehydratase (ALAD) activity was determined in 58 lead workers
out of 76 subjects.
Results: NADS activity in the lead workers ranged from 0.08 to 1.1 μmol/h per g of hemoglobin (gHb) and decreased linearly (r = − 0.867) as Pb-B increased up to 81.6 μg/dl. The pattern of depressed activity of NADS was different from that of ALAD
activity, which decreased rapidly and reached a plateau at the Pb-B level between 40 and 60 μg/dl. The Pb-B levels inducing
50% inhibition of the enzyme activities were calculated to be 43 μg/dl and 20 μg/dl for NADS and ALAD, respectively. At the
Pb-B level of 40 μg/dl, NADS activity showed high validity (1.77) with predictivity of 0.92 at the cut-off level of 0.4 μmol/h
per gHb, which were higher than those of ALAD activity.
Conclusions: These results show an apparent dose-effect relationship of NADS activity versus Pb-B. NADS activity can be used for the
biological monitoring of lead exposure.
Received: 28 October 1996 / Accepted: 7 February 1997 相似文献