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101.
Correlation of Hexokinase Content and Basal Energy Metabolism in Discrete Regions of Rat Brain 总被引:1,自引:1,他引:0
Brain hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) levels in seven regions of rat brain were estimated by photometric measurement of immunofluorescence in cryostat-cut sections. When compared with basal rates of glucose metabolism in these regions, estimated by the 6-[14C]glucose method, a significant correlation was observed. Thus, hexokinase content reflects metabolic energy demands. 相似文献
102.
Abstract: We measured hexokinase (EC 2.7.1.1) activity in particulate and soluble fractions isolated from bullfrog ( Rana catesbeiana ) retinas. Seventy-three percent of the hexokinase (HK) activity was associated with the particulate fraction, 27% with the soluble fraction. Both HK fractions could phosphorylate fructose, glucose, 2-deoxy-d-glucose, and mannose, but not galactose. The K m for glucose was 0.14 m M , for 2-deoxy-d-glucose. 3.6 m M . With glucose as substrate, the V max for particulate HK was 125–148 μ M retina−1 min−1 , for soluble HK, 37 μ M retina−1 min−1 . Product inhibition of particulate HK activity by glucose 6-phosphate was marked, whereas 2-deoxy-d-glucose 6-phosphate did not inhibit the activity. Cyclic AMP stimulated the HK activity of both retinal fractions nearly twofold at concentrations of 0.2–0.8 m M; AMP was much less effective in this regard. 相似文献
103.
Trypanosoma brucei: preparation and some properties of a multienzyme complex catalysing part of the glycolytic pathway 总被引:5,自引:0,他引:5
After grinding Trypanosoma brucei with alumina or silicon carbide, it is possible to prepare a multienzyme complex which catalyses the breakdown of glucose to l-glycerol-3-phosphate and 3-phosphoglycerate. The complex sediments with the postnuclear large granule fraction which pellets at 14,500g; it is also eluted in the void volume during Bio-Gel A-5m column chromatography of a cell homogenate. During isopycnic sucrose gradient centrifugation, the multienzyme complex bands at a density of 1.22 g/ml. Because this is the density of T. brucei microbodies, and because Triton X-100 treatment of the material greatly enhances the activities of its component enzymes, we conclude that the multienzyme complex is probably located in the microbodies of the bloodstream long slender forms of T. brucei. 相似文献
104.
Effect of Hypo- and Hyperthyroidism on Hexokinase in the Developing Cerebellum of the Rat 总被引:2,自引:2,他引:0
Abstract: Total hexokinase levels (units/g tissue) have been measured during postnatal development of the cerebellum in control, hypothyroid, and hyperthyroid rats. In addition, distribution of hexokinase in the developing cerebellum has been observed with an immunofluorescence method. Hypothyroidism delays the normally observed postnatal increase in total hexokinase activity, whereas hyperthyroidism accelerates the increase. In normal animals, hexokinase levels in maturing Purkinje cells pass through a transient increase, with maximal levels at approximately 8 days postnatally followed by rapid decline to relatively low levels by 12 days; hypothyroidism delays this transient increase and subsequent decline, but hyperthyroidism does not appear to affect markedly the timing of this phenomenon. Cerebellar glomeruli are relatively enriched in hexokinase content, as judged by their intense fluorescence. Hypothyroidism delays the development of intensely stained glomeruli. Hyperthyroidism did not appear to cause precocious increase in numbers of glomeruli but may have increased the rate at which the hexokinase was assimilated by newly formed glomeruli. The effects of hypo- and hyperthyroidism on total cerebellar hexokinase levels are interpreted in terms of the effect of thyroid hormone on the biochemical maturation of synaptic structures rich in hexokinase. 相似文献
105.
Competitive Inhibition of Human Brain Hexokinase by Metrizamide and Related Compounds 总被引:1,自引:1,他引:0
Abstract: We have compared the competitive inhibitory effects of 2-deoxyglucose, glucosamine, N -acetylglucosamine, N -benzoylglucosamine, and the commonly used radiographic and density gradient agent metrizamide (2-[3 - acetamido - 2,4,6 - triiodo -5-( N - methylacetamido) benzamido]-2-deoxyglucose) on the mitochondrial and soluble forms of human brain hexokinase. Metrizamide produces a classical competitive inhibition with glucose for human brain hexokinase, with K i s of 2.8 and 2.5 m M , respectively, for the mitochondrial and soluble forms. Glucosamine exhibited K i s of 0.58 and 0.29 m M , while 2-deoxyglucose exhibited K i s of 0.074 and 0.15 m M and N -acetylglucosamine 0.098 and 0.092 m M for these two forms, respectively. N -Benzoylglucosamine was by far the most effective inhibitor tested, with K i values of 0.0086 and 0.022 m M , respectively. In order of increasing potency as a competitive inhibitor for mitochondrial hexokinase are metrizamide, glucosamine, N -acetylglucosamine, 2-deoxyglucose, and N -benzoylglucosamine. For the soluble form of the enzyme in increasing potency are metrizamide, glucosamine, 2-deoxyglucose, N -acetylglucosamine, and N -benzoylglucosamine. Since N -benzoylglucosamine was over 100 times more potent than metrizamide, some of the effects of metrizamide could be due to contamination by N -benzoylglucosamine. However, gas chromatography-mass spectrometry analysis of metrizamide did not indicate the presence of N -benzoylglucosamine. In addition, column chromatographic separation of commercially available metrizamide and reconstitution of freeze-dried eluate fractions localized the inhibitory effect to the metrizamide peak. 相似文献
106.
本文介绍一种特异、灵敏、简便人血清载脂蛋白CⅡ(apoCⅡ)竞争性酶兔疫测定法(Competitive Enzyme Immunoassay,CEIA)。单价特异抗体由免疫家兔获得。采用部分纯化的apoCs包被聚苯乙烯板。羊抗兔γ-球蛋白酶交联物用辣根过氧化物酶按简化过碘酸钠法制备。apoCⅠ、AⅠ、AⅡ以及LDL无交叉反应。本法最小检测量为25ng,标准曲线工作范围是1.5~30.0mg%,板内及板间变异系数分别为6.5~7.8%及6.6~11.0%,回收率为107.5%;185例正常人血清apoCⅡ含量,男5.1±1.9mg%(n=95),女4.8±1.7mg%(n=90)。 相似文献
107.
Changes in the activity of hexokinase and lactate dehydrogenase isoenzymes in the three brain regions and heart were studied
in the 6-Aminonicotinamide-treated rats. Drug administration decreased the particulate hexokinase and lactate dehydrogenase
activity, but increased the soluble hexokinase 相似文献
108.
目的探讨RNA干扰血管生成素样蛋白7 (Angptl7)基因对血管紧张素Ⅱ(AngⅡ)诱导的血管平滑肌细胞(VSMC)炎症因子的影响及其作用机制。 方法体外培养人VSMC,分为常规F12K培养基培养(对照)和1 μg/mL AngII培养24 h。VSMC用AngⅡ(1 μg/mL)处理24 h后,采用siRNA-Angptl7和阴性对照siRNA-NC在Lipofectamine 2000介导下转染VSMC。RT-qPCR检测mRNA表达水平;Griess反应测定一氧化氮(NO)含量;蛋白免疫印记法检测相关蛋白的改变;酶联免疫吸附法检测VSMC中炎症因子肿瘤坏死因子α(TNF-α)、白细胞介素-1β (IL-1β)和IL-6水平。多组间比较采用单因素方差分析,组间两两比较采用LSD-t检验,两组间比较采用独立样本t检验。 结果与对照比较,1 μg/mL AngⅡ处理可促进VSMC中Angptl7 mRNA (0.97±0.06比3.05±0.21)和蛋白表达(1.01±0.12比1.61±0.14),亦可促进VSMC中IL-1β[(45.21±8.10)比(126.17±11.77) pg/mL]、IL-6[(50.50±7.51)比(108.50±9.51)pg/mL]和TNF-α的表达[(60.77±9.58)比(185.67±17.35)pg/mL],差异有统计学意义(P均< 0.01)。与对照和转染siRNA-NC相比,转染siRNA-Angptl7下调Angptl7蛋白表达(0.99±0.12,0.98±0.12比0.44±0.14,P < 0.01)。与AngⅡ干预组相比,siRNA-Angptl7降低AngⅡ介导的VSMC炎症反应相关蛋白TNF-α、IL-6和IL-1β的表达,核因子κB (NF-κB)/诱导型一氧化氮合酶(iNOS)/环氧化酶2 (COX-2)信号通路相关蛋白NF-κB、iNOS和COX-2表达及NO含量亦降低,差异有统计学意义(P均< 0.01)。与siRNA-NC相比,siRNA-Angptl7组AngⅡ诱导的VSMC炎症反应相关蛋白TNF-α (0.99±0.13比0.51±0.12)、IL-6 (1.00±0.12比0.38±0.05)和IL-1β的表达(0.99±0.14比0.48±0.11),NF-κB (1.00±0.10比0.42±0.08)、iNOS (1.02±0.12比0.42±0.10)和COX-2表达(1.00±0.11比0.52±0.12)均降低,NO含量[(54.78±2.76)比(18.08±3.61)μmol/L]亦降低,差异有统计学意义(P均< 0.01)。 结论AngⅡ可通过Angptl7促进VSMC炎症反应,下调Angptl7蛋白表达可以抑制VSMC的炎症反应,其作用机制可能与抑制NF-κB/iNOS-COX-2信号通路有关。 相似文献
109.
《Bioorganic & medicinal chemistry letters》2019,29(16):2129-2135
A series of conjugates of podophyllotoxin and coumarin were prepared using the click reaction, and their cytotoxicities against A549, HepG2, HeLa, and LoVo cells were evaluated. Among them, compound 14e exhibited the strongest cytotoxicities against these cancer cells with IC50 values of 4.9–17.5 μM. Furthermore, 14e disrupted microtubules and induced cell cycle arrest at G1 phase by regulating P21 and Cyclin D1 in LoVo cells. In addition, 14e bond CT DNA and selectively inhibited Topo IIβ over Topo IIα. Molecular docking model showed that 14e appeared to form stable hydrogen bonds with several DNA bases and residue Gln778. Taken together, these conjugates have the potential to be developed as anti-tumor drugs. 相似文献
110.
Martinez J Nguyen LD Hinderlich S Zimmer R Tauberger E Reutter W Saenger W Fan H Moniot S 《The Journal of biological chemistry》2012,287(17):13656-13665
Sialic acids are essential components of membrane glycoconjugates. They are responsible for the interaction, structure, and functionality of all deuterostome cells and have major functions in cellular processes in health and diseases. The key enzyme of the biosynthesis of sialic acid is the bifunctional UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase that transforms UDP-N-acetylglucosamine to N-acetylmannosamine (ManNAc) followed by its phosphorylation to ManNAc 6-phosphate and has a direct impact on the sialylation of cell surface components. Here, we present the crystal structures of the human N-acetylmannosamine kinase (MNK) domain of UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase in complexes with ManNAc at 1.64 Å resolution, MNK·ManNAc·ADP (1.82 Å) and MNK·ManNAc 6-phosphate·ADP (2.10 Å). Our findings offer detailed insights in the active center of MNK and serve as a structural basis to design inhibitors. We synthesized a novel inhibitor, 6-O-acetyl-ManNAc, which is more potent than those previously tested. Specific inhibitors of sialic acid biosynthesis may serve to further study biological functions of sialic acid. 相似文献