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1.
Rat liver microsomal 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase was activated by 50% at a concentration of 0.4 mM 2,3-diphosphoglyceric acid (DPG) and by 11-fold at 10 mM DPG. DPG also prevented the inactivation of HMG-CoA reductase by ATP and Mg++. Rat liver microsomal HMG-CoA reductase prepared in the presence of 1 mM DPG was significantly more active than when prepared in the absence of DPG. Activation of the enzyme by DPG and protection of the enzyme against inhibition by ATP and Mg++ by DPG were also observed with solubilized HMG-CoA reductase.  相似文献   

2.
Summary Rat liver microsomal 3-hydroxy-3-methylgularyl CoA (HMG-CoA) reductase was activated by 50% at a concentration of 0.4 mM 2,3-diphosphoglyceric acid (DPG) and by 11-fold at 10 mM DPG. DPG also prevented the inactivation of HMG-CoA reductase by ATP and Mg++. Rat liver microsomal HMG-CoA reductase prepared in the presence of 1 mM DPG was significantly more active than when prepared in the absence of DPG. Activation of the enzyme by DPG and protection of the enzyme against inhibition by ATP and Mg++ by DPG were also observed with solubilized HMG-CoA reductase.This work was supported by Research Award # 697 G2-1 from the American Heart Association, Greater Los Angeles Affiliate, and by grant # 1R01 HL22672 from the National Institutes of Health. We thank M. Brun and M. Curtis for their excellent technical assistance.  相似文献   

3.
Summary The increase in methemoglobin reductase activity in human erythrocytes upon incubation with inosine, phosphate, pyruvate occurs only in the presence of methylene blue. No difference in activity of the methemoglobin reductases was observed between enzyme extracts of fresh cells and aged cells.  相似文献   

4.
The increase in methemoglobin reductase activity in human erythrocytes upon incubation with inosine, phosphate, pyruvate occurs only in the presence of methylene blue. No difference in activity of the methemoglobin reductases was observed between enzyme extracts of fresh cells and aged cells.  相似文献   

5.
The effect of dried oyster mushroom (Pleurotus ostreatus) on cholesterol (C) content in serum, in lipoproteins and in liver, and on the activity of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase in liver microsomes, was studied in male rats (strain Wistar, initial body weight 75 g) fed on low-cholesterol (9 mg/100 g) and high-cholesterol (0.3%) diets. Addition of 5% oyster mushroom to both diets reduced significantly the C-content in serum (by 30%), in very-low- and low-density lipoproteins (in a 11 ratio to the decrease of total serum C) and in liver (by 50%), as well as the activity of HMG-CoA reductase (by more than 30%).  相似文献   

6.
7.
Summary The cells obtained from anaerobic cultures ofA. aerogenes contain both a hydrogenase and a fumaric reductase, but lack one or several electron transporters necessary for the coupling of the two enzymes. It is possible to measure the fumaric reductase activity of the extracts in the presence of hydrogen, hydrogenase and benzyl viologen, using the Warburg manometric technique. In anaerobic cultures the reductase is an inducible enzyme. In aerobic cultures its formation is strongly repressed by atmospheric oxygen.  相似文献   

8.
Human Hep27 was originally isolated from growth-arrested HepG2 cells and identified as a member of the superfamily of short-chain dehydrogenases/reductases (SDR). Its substrate specificity has not been determined, but a cross-species comparison suggests that it occurs in widely divergent species, such as human, Cenorhabditis elegans, Drosophila and Arabidopsis thaliana. In this study, Hep27 was expressed as a His6 fusion protein, and subjected to a substrate screen, using a compound library of SDR substrates, comprising steroids, retinoids, sugars and carbonyl compounds. Whereas no steroid dehydrogenase or retinoid activity was detected, it was found that Hep27 catalyzed the NADPH-dependent reduction of dicarbonyl compounds, like 3,4-hexanedione and 1-phenyl-1,2-propanedione with similar turnover numbers as DCXR (a mitochondrial dicarbonyl reductase/xylulose reductase). In contrast, Hep27 does not convert sugar substrates like xylulose or threose. Based on its substrate specificity and expression in endothelial tissues, it is suggested that Hep27 functions as a dicarbonyl reductase in enzymatic inactivation of reactive carbonyls, involved in covalent modification of cellular components. Received 16 January 2006; received after revision 28 February 2006; accepted 31 March 2006  相似文献   

9.
Aldose reductase and aldehyde reductase belong to the aldo-keto reductase superfamily of enzymes whose members are responsible for a wide variety of biological functions. Aldose reductase has been identified as the first enzyme involved in the polyol pathway of glucose metabolism which converts glucose into sorbitol. Glucose over-utilization through the polyol pathway has been linked to tissue-based pathologies associated with diabetes complications, which make the development of a potent aldose reductase inhibitor an obvious and attractive strategy to prevent or delay the onset and progression of the complications. Structural studies of aldose reductase and the homologous aldehyde reductase in complex with inhibitor were carried out to explain the difference in the potency of enzyme inhibition. The aim of this review is to provide a comprehensive summary of previous studies to aid the development of aldose reductase inhibitors that may have less toxicity problems than the currently available ones. Received 4 December 2006; received after revision 12 February 2007; accepted 20 April 2007  相似文献   

10.
Summary Studies of the inactivation of the rice nitrate reductase showed that the nitrate-reducing moiety and not the diaphorase moiety was reversibly inactivated by NADH and cyanide. Ferricyanide could reverse the inactivation, and nitrate could protect the enzyme against inactivation. Although the general characteristics of the reversible inactivation of rice nitrate reductase appeared similar to those of the algal nitrate reductase, it was found that the rice enzyme was automatically reactivated when NADH and cyanide were removed. Attempts to isolate inactivated nitrate reductase from ammonium-treated tissue were unsuccessful.  相似文献   

11.
Summary Nitrate reductase was protected from inactivation in wheat leaf extracts by NADH, while NADPH was less effective. NAD, NADP or adenylates did not affect nitrate reductase inactivation in vitro. Glutamine synthetase was more stable than nitrate reductase and was protected from inactivation by ATP. ADP, AMP or pyridine nucleotides had no or only a minor effect on the decrease of glutamine synthetase activity in extracts. The caseolytic activity extracted from senescing leaves was slightly decreased by NADH and NADPH but this effect was not sufficient to explain the stabilization of nitrate reductase by NADH. Oxidized pyridine nucleotides and adenylates had no major effect on the caseolytic activity under the conditions used.This work was supported by grant 3.067-0.81 from the Swiss National Science Foundation. Author for correspondence: U.F.  相似文献   

12.
Summary No evidence of the existence of a single indoleacetaldehyde mutase in microorganisms is available. Different results from studies on living cultures and cell-free extracts ofEndomycopsis vernalis, Hansenula anomala, Torulopsis utilis andAgrobacterium tumefaciens indicate the participation of 2 different enzymes: an aldehyde dehydrogenase and an aldehyde reductase.  相似文献   

13.
Aldose reductase catalyzes the first step in the polyol pathway and is thought to be involved in the pathogenesis of diabetic complications. In addition to polyol synthesis, aldose reductase may have multiple other activities that intersect with signal processing and oxidative defense mechanisms. Multiple aldose reductase-like proteins have been discovered to have structures and catalytic properties that broadly overlap those of aldose reductase. This chapter will summarize new insights into properties and functions of aldose reductase and closely related members of the aldo-keto reductase enzyme superfamily.  相似文献   

14.
Digoxin and ouabain are steroid drugs that inhibit the Na+/K+-ATPase, and are widely used in the treatment of heart diseases. They may also have additional effects, such as on metabolism of steroid hormones, although until now no evidence has been provided about the effects of these cardioactive glycosides on the synthesis of cholesterol. Here we report that digoxin and ouabain increased the synthesis of cholesterol in human liver HepG2 cells, enhancing the activity and the expression of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the rate-limiting enzyme of the cholesterol synthesis. This effect was mediated by the binding of the sterol regulatory element binding protein-2 (SREBP-2) to the HMGCR promoter, and was lost in cells silenced for SREBP-2 or loaded with increasing amounts of cholesterol. Digoxin and ouabain competed with cholesterol for binding to the SREBP-cleavage-activating protein, and are critical regulators of cholesterol synthesis in human liver cells. Received 10 January 2009; received after revision 11 February 2009; accepted 6 March 2009  相似文献   

15.
This review highlights progress in dissecting how plant nitrate reductase (NR) activity is regulated by Ca2+, protein kinases, protein kinase kinases, protein phosphatases, 14-3-3 proteins and protease(s). The signalling components that regulate NR have also been discovered to target other enzymes of metabolism, vesicle trafficking and cellular signalling. Extracellular sugars exert a major impact on the 14-3-3-binding status and stability of many target proteins, including NR in plants, whereas other stimuli affect the regulation of some targets and not others. We thus begin to see how selective or global switches in cellular behaviour are triggered by regulatory networks in response to different environmental stimuli. Surprisingly, the question of how changes in NR activity actually affect the rate of nitrate assimilation is turning out to be a tough problem.  相似文献   

16.
17.
We compared the effects ofAlzheimer's peptide (Abeta1-42), a,-antichymotrypsin (ACT) and an ACT/Abeta1-42 mixture on human glioma DK-MG cells. The solution of Abeta (5 microM) formed by 2-h incubation at room temperature induced tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 levels by 55 and 45%, respectively, and increased gelatinase B activity by 67%, while exposure of cells to the ACT/Abeta1-42 mixture (1:10 molar ratio ACT: Abeta1-42) under the same experimental conditions showed no effect on IL-6 levels or gelatinase B activity, but strongly induced TNF-alpha (by 190%), compared to the controls. Stimulation of the cells with Abeta1-42 alone, but not with ACT, increased by about 20% low-density lipoprotein (LDL) uptake and mRNA levels for LDL receptor and HMG-CoA reductase, while the ACT/Abeta1-42 mixture significantly increased LDL uptake (by 50%), up-regulated mRNA levels for LDL receptor and HMG-CoA reductase by 48 and 63%, respectively, and increased lipid accumulation by about 20-fold. These data suggest a possible new role for Abeta in Alzheimer's disease through its interaction with the inflammatory reactant, ACT.  相似文献   

18.
Mammalian thioredoxin reductase (TrxR) is a selenoprotein with three existing isoenzymes (TrxR1, TrxR2, and TrxR3), which is found primarily intracellularly but also in extracellular fluids. The main substrate thioredoxin (Trx) is similarly found (as Trx1 and Trx2) in various intracellular compartments, in blood plasma, and is the cell’s major disulfide reductase. Thioredoxin reductase is necessary as a NADPH-dependent reducing agent in biochemical reactions involving Trx. Genetic and environmental factors like selenium status influence the activity of TrxR. Research shows that the Trx/TrxR system plays a significant role in the physiology of the adipose tissue, in carbohydrate metabolism, insulin production and sensitivity, blood pressure regulation, inflammation, chemotactic activity of macrophages, and atherogenesis. Based on recent research, it has been reported that the modulation of the Trx/TrxR system may be considered as a new target in the management of the metabolic syndrome, insulin resistance, and type 2 diabetes, as well as in the treatment of hypertension and atherosclerosis. In this review evidence about a possible role of this system as a marker of the metabolic syndrome is reported.  相似文献   

19.
Aldose reductase is involved in the polyol pathway, catalyzing the reduction of glucose to sorbitol. However, due to pronounced binding site adaptations, the enzyme can operate on a broad palette of structurally diverse substrates ranging from small aliphatic and aromatic aldehydes up to steroid-type ligands. A comparative analysis of the presently accessible crystal structures of aldose reductase complexes reveals four binding-competent protein conformations. Additional relevant conformers are detected through molecular dynamics simulations. They indicate an equilibrium of several conformers which is shifted towards the binding-competent geometries upon ligand binding. Such a manifold system with several alternative binding site conformers requires some tailored concepts in virtual screening. We followed two strategies, both successfully suggesting new micromolar inhibitors. In a first attempt, we concentrated on one preferred conformer and performed a virtual screening, assuming that the binding pocket of aldose reductase adopts only this conformation. In a second approach, we followed a ligand superpositioning method. Ligands were extracted in their bound conformations from three different crystal structures, all accommodating the ligands with different active site conformations. After merging these ligands into one supermolecule, mutual alignments were computed, taking candidate ligands from a screening database. The latter strategy also retrieved several structurally new inhibitors of micromolar potency.  相似文献   

20.
The regulation of the protein synthesis has a crucial role in governing the eukaryotic cell growth. Subtle changes of proteins involved in the translation process may alter the rate of the protein synthesis and modify the cell fate by shifting the balance from normal status into a tumoral or apoptotic one. The largest eukaryotic initiation factor involved in translation regulation is eIF3. Amongst the 13 factors constituting eIF3, the f subunit finely regulates this balance in a cell-type-specific manner. Loss of this factor causes malignancy in several cells, and atrophy in normal muscle cells. The intracellular interacting partners which influence its physiological significance in both cancer and muscle cells are detailed in this review. By delineating the global interaction network of this factor and by clarifying its intracellular role, it becomes apparent that the f subunit represents a promising candidate molecule to use for biotherapeutic applications.  相似文献   

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