Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphypyridoxyl trifluoroethylamine has been synthesized as an active site-directed 19F NMR probe for aspartate transaminase. This coenzyme derivative adds stoichiometrically to the apotransaminase as observed by both fluorescence and circular dichroism measurements. The fluorinated phosphypyridoxamine derivative, when bound to the apotransaminase, will not dissociate upon extensive dialysis or passage through Sephadex G-25. The compound behaves as a pyridoxamine phosphate derivative and not as a coenzyme-substrate complex, since both competing anions and dicarboxylic acid inhibitors still bind to the phosphopyridoxyl trifluoroethylamine enzyme. The 19F NMR spectra of the enzyme-bound phosphopyridoxyl trifluoroethylamine were measured as a function of pH, ionic strength, and temperature. The 19F MNR of the enzyme-bound coenzyme derivative revealed no predetermined asymmetry in the subunits of aspartate transaminase insolution in terms of differences in chemical shift or resonance line shape between the two environments. A pH-dependent chemical shift change of the single 19F resonance was observed, which is consistent with the influence of a single ionization with an apparent pKa of 8.4 in 0.10 M KCl at 30 degrees. Increasing the ionic strength resulted in increasing values for the observed pKa, the highest recorded value was 9.1 in 3.0 M KCl. The temperature dependence of the pH titration of the chemical shift gives deltaH' of ionization of 10.5 kcal/mol. The evidence suggests a possible epsilon-amino group, electrostatically affected by positive charges, being responsible for the titration effect of the active site-bound fluorine derivative of pyridoxamine phosphate.
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PMID:Fluorine-19 as a covalent active site-directed magnetic resonance probe in aspartate transaminase. 0 32

At pH 7, the apoenzyme of carboxymethylated and acylated aspartate aminotransferase reacts selectively with 1,5-difluoro-2,4-dinitrobenzene to form a single intramolecular covalent bond with the epsilon-amino group of the functional lysine residue located within the active centre. On shifting the pH to 9, the second fluorine atom of the bifunctional reagent is substituted with the sterically adjacent side groups of cysteine and tyrosine residues. The modified apoenzyme was subjected to partial proteolysis with pronase, and the digest was used to obtain and isolate the labeled products and to localize amino acid residues involved in the reaction. The established structures of several peptides containing Cys-2,4-dinitrobenzene-Lys and Tyr-2,4-dinitrobenzene-Lys allowed the identification of the amino acid residues involved in the reaction with the bifunctional reagent as Lys 258, Cys 390 and probably Tyr-70. The residues of Cys and Tyr are thus located at a distance of approximately 5 A (the length of the dinitrophenylene bridge) from the lysine residue forming an aldimine bond with pyridoxal 5'-phosphate in the active site.
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PMID:Two-step modification of aspartate aminotransferase with 1,5-difluoro-2,4-dinitrobenzene. Cross-link localization. 66 10

2'-Fluoro-5-iodoarabinosylcytosine (FIAC) has potent antiviral activity in vivo against herpes simplex virus types 1 and 2 and cytomegalovirus. For examination of the clinical efficacy of FIAC, a randomized, double-blind study of FIAC versus adenine arabinoside (ara-A) was conducted in 34 immunosuppressed individuals with varicella-zoster virus infections. The median time to the appearance of the last new lesion was shorter in patients who received FIAC relative to those who received ara-A (two versus five days, respectively; P less than .001) FIAC also reduced pain and accelerated initial crusting within 72 hr in a significantly greater proportion of patients when compared with ara-A (P = .004 and P = .0009, respectively). FIAC caused few toxic reactions (mild nausea and transient elevation in activity of serum aspartate aminotransferase). Thus FIAC is therapeutically superior to ara-A for the treatment of varicella-zoster virus infections in immunosuppressed subjects.
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PMID:2'-Fluoro-5-iodoarabinosylcytosine, a new potent antiviral agent: efficacy in immunosuppressed individuals with herpes zoster. 352 94

Activities of glutamic-oxalacetic transaminase, glutamate dehydrogenase, gamma-glutamyl transferase were reduced in unstimulated pooled saliva of 15-year-old adolescents with endemic fluorosis, vs. those without fluorosis. This point to reduced production of glutamate which is indispensable for bacterial growth. The activity of acid phosphatase in pooled stimulated with 1% pilocarpin saliva of rats fed a water ration with 5 and 20 mg/liter fluorine in comparison with control rats fed water with fluorine concentration of 0.21 mg/liter. Noteworthy that alkaline phosphatase activity was virtually unchanged at fluorine concentrations 5 and 20 mg/liter in the water. The significance of the results as far as it regards the pathogenesis of caries and fluorosis is discussed.
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PMID:[The enzymes of glutamate and organic phosphate metabolism in the saliva in fluorosis (clinical and experimental research)]. 748 2

The influence of sodium fluoride on the course of repair process in the mechanically injured rat bone was studied. Thirty six male Wistar rats aged 5 months, weighing 460-540 g were investigated. The animals lived under standard conditions and were fed ad libidum with the standard LSM food including 0.7 mg/kg of fluorine on the average. The animals randomly divided into 3 groups that comprised study and control groups, 6 rats each. The rats in the first group were given water with 20 mg (1.05 mmol) of sodium fluoride per kg of body weight for 24 h over a period of 2 weeks--group Ia. In the second group--IIa--animals were given water with sodium fluoride at a dose of 1.5 mmol/kg b.w./24 h for a period of 4 weeks. In the third group--IIIa--the animals were given sodium fluoride in a dose of 1.5 mmol/kg b.w./24 h for a period of 6 weeks. The rats from the control groups I, II and III were given water without sodium fluoride for the period of 2, 4 and 6 weeks, respectively. At the beginning of the experiment a hole was drilled in both femoral bones in rat under barbiturate anaesthesia. According to the protocol the rats underwent ether euthanasia after 2, 4 and 6 weeks after surgery and the following samples were collected: blood from the heart for biochemical studies and both femoral bones for biochemical and histological studies. The following parameters were evaluated in blood serum: fluorine, calcium, magnesium contents, serum concentrations of urea, creatinine, bilirubin and activity levels of enzymes: aspartate aminotransferase, alanine aminotransferase, cholinesterase, base phosphatase. Fluorine, calcium magnesium and zinc contents were estimated in bone samples. The concentration of fluorine ions in animal serum after 2, 4 and 6 weeks of experiment increased significantly as compared with the corresponding controls. The highest fluorine concentrations were observed in serum of rats supplemented with NaF for 6 weeks. The fluorine concentrations in the bone tissue and fresh and dried granulation tissues in all studied groups also revealed statistically significant increase as compared to the controls. The rats fed with sodium fluoride for the period of 6 weeks revealed statistically significant increase of serum magnesium concentration as compared to the remaining study groups. Bone magnesium concentrations in animals fed with NaF for the period of 2 and 6 weeks were higher as compared to the corresponding control groups, with the highest differences observed after 6 weeks of experiment. Animals fed with sodium fluoride for the period of 6 weeks revealed increased serum calcium concentrations as compared to the study groups after 2 and 4 weeks of experiment. Similar results were achieved in bone tissue samples (Fig. 1 and 2, Tab. 1-6). Basing on the achieved results in biochemical studies and histological pictures it should be assumed that laboratory animals fed with sodium fluoride in doses recognised as non-toxic reveal intensified healing process within mechanically injured bones. The use of sodium fluoride led to accelerated chondrogenesis process in the area of insufficiently perfused bone, osteogenesis including temporary callus formation and mineralization of the new bone, as well as remodelling into mature lamellar bone. The greatest differences in the repair dynamics for both groups occurred between the second and fourth week of experiment. These results could be the base of clinical studies on application of the sodium fluoride in the acceleration of fracture healing.
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PMID:[Evaluation of the repair process in mechanically injured rat bone stimulated by sodium fluoride with non-toxic doses]. 1090 90

Drug interactions are the side effect of administration of two or more drugs or a drug-food combination. Although some drug interactions are intentional and beneficial to the patient, the majority are unintentional and associated with a potentially harmful effect. The aim of this study was to search for interactions in rats between fluoride and zinc administered orally for 12 weeks and to elucidate any potential toxicological and therapeutic consequences. 60 male Wistar rats were divided into six groups of ten rats each and exposed to: 1. controls (distilled water); 2. sodium fluoride (NaF); 3. low-dose zinc (Zn); 4. high-dose zinc; 5. NaF + low-dose Zn; 6. NaF + high-dose Zn. At the end of the experiment the content of F- and Zn+ in serum, urine, incisors, femur and mandible was measured and densitometry of femoral bones was performed. Serum alkaline phosphatase, alanine and aspartate aminotransferase activities, as well as bilirubin and creatinine concentrations were determined to confirm non-toxicity of fluoride dose. Animals receiving NaF only demonstrated higher content of fluorine in serum, urine bones and teeth. Zinc concentrations in serum, urine, bones and teeth were elevated in rats receiving zinc with or without NaF. Fluorine accumulation in bones and teeth was reduced by Zn, but in general the effect lacked statistical significance. Zinc slightly reduced the concentrations of fluorine in serum and urine. Sodium fluoride slightly reduced the concentration of zinc in serum and urine. Bone mineral content (BMC) was significantly increased by NaF and was not further increased by co-administration of zinc. No changes in serum alkaline phosphatase, alanine and aspartate aminotransferase activities, bilirubin and creatinine concentrations were detected. In conclusion, simultaneous administration of fluorine and zinc may be beneficial for prevention and treatment of pathologic conditions in bones and teeth and is not accompanied by an increase in fluorine levels which could be responsible for toxicological symptoms.
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PMID:[Interaction between fluorine and zinc after long-term oral administration into the digestive system of rats]. 1460 70

This work is an experimental response to an intriguing paper recently published by Catlow and co-workers, which looked at the computational feasibility of fluorine location in three different all-silica zeotypes (Attfield, M. P.; Catlow, C. R. A.; Sokol, A. A. Chem. Mater. 2001, 13, 4708). The materials were chosen as representative of three unique host locations. Our present work examined the synthesis of zeotypes AST, IFR, and MTT using organo-cations with a strong preference for crystallizing these structures. We studied the effect of reaction time and the H(2)O/SiO(2) reactant ratio. The latter is probably the most important function in these zeolite crystallizations that use HF. As reaction conditions became more dilute, AST gave way to SGT and IFR to MTW as host structures, while the MTT synthesis was invariant. Our reactions were studied in terms of product yield vs time, product organo-cation content, fluorine content, and the representative (29)Si and (19)F NMR spectra for certain samples. A single crystal study was carried out for a sample of MTT. Our results showed that, consistent with other recent studies, low H(2)O/SiO(2) reactant ratios lead to more open framework host structures (i.e., IFR vs MTW), and there is typically a higher uptake of organo-cation and fluorine. The structure may well contain a higher population of 4-rings within the silicate substructure. While MTT that contains no 4-rings was chosen as the best possible candidate to achieve an ion-pair for the organo-cation and fluoride anion within the silicate host, both NMR and single crystal work confirm that fluoride is bonded to a 5-coordinate silica center within the lattice.
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PMID:Studies on the role of fluoride ion vs reaction concentration in zeolite synthesis. 1685 Oct 58

Three-month studies were performed on 18 adult rabbits of New Zealand breed divided into three groups, with six animals in each: a control group on standard diet, a cholesterol group receiving 500 mg of cholesterol/100 g of feed per rabbit per 24 h (CH group), and a cholesterol + fluorine group (CH + F group) receiving 500 mg of cholesterol/100 g of feed per rabbit per 24 h and 3 mg of F(-)/kg of body weight per 24 h. The conducted studies proved that cholesterol in the applied dosage (500 mg cholesterol per rabbit per 24 h) has an atherogenic action. Fluoride ions administered together with a 500-mg cholesterol atherogenic diet inhibit the atheromatosic changes in the aorta. The concentration of plasma cholesterol was elevated in both study groups when compared to the control group but decreased in the CH + F group when compare to the CH group. The influence of fluoride ions has been examined upon the activity of alanine aminotransferase, aspartate aminotransferase, and glutamate dehydrogenase (GLDH) in the plasma in the liver of rabbits in the course of experimental hypercholesterolemia. Increase in the activity of study enzymes has been observed in the blood plasma, which may be due to damage occurring to hepatocytes of the animals examined (a statistically significant increase in the activity of GLDH in the plasma). In the liver, the inhibition of activity for all examined enzymes has been observed in the group of rabbits with hypercholesterolemia, which testifies the disturbances in protein metabolism in examined animals. The addition of sodium fluoride to the diet rich in cholesterol results in "removing the block" on those activities, which increase. We suppose that the permeability of the hepatocyte membrane was elevated, so the activities of examined enzymes increased in the plasma ("escape" to plasma). On the one hand, fluoride ions result in probable lesion of hepatocytes membranes; on the other hand, they inhibit the atheromatosic changes in the aorta.
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PMID:The influence of fluoride ions upon selected enzymes of protein metabolism in blood plasma of rabbits with hypercholesterolemia. 1850

Fluoxetine (Flux) is a fluorine-containing drug that selectively inhibits serotonin reuptake. It is widely prescribed as a treatment for depression disorders. Hepatic side effects have been reported during Flux therapy. These reports led us to investigate the involvement of oxidative stress mechanisms in liver injury caused by Flux. It has been shown that exposure to fluoride (F(-)) induces excessive production of free radicals and affects the antioxidant defense system. Based on this knowledge, we examined the F(-) concentration in serum and urine during administration of Flux. In our study, the effects of one month of Flux treatment on lipid and protein peroxidation, the concentration of uric acid in the liver and the activity of transaminases and transferases in the serum were investigated in rats. Eighteen adult male Wistar rats were divided into three equal groups of six animals each: (I) controls who drank tap water and received 1 ml of tap water intragastrically; (II) animals that received 8 mg Flux/kg bw/day intragastrically; and (III) animals that received 24 mg Flux/kg bw/day intragastrically. Flux treatment increased of the levels of carbonyl groups, thiobarbituric acid reactive species (TBARS) and the uric acid content in the liver. The activities of alanine transaminase (ALT), aspartate transaminase (AST) and glutathione-S transferase (GST) increased in the serum of the treated groups. The Flux levels in the plasma of the treated rats increased significantly in a dose-dependent manner. We observed no changes in the concentration of fluoride in either the serum or the urine of treated rats compared to the control group. In conclusion, our study indicates that Flux induces liver damage and mediates free radical reactions. Our data also indicate that Flux does not release F(-) during metabolism and does not affect physiological levels of F(-) in the serum or urine.
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PMID:Impact of fluoxetine on liver damage in rats. 2160 99

Diethylnitrosamine (DEN), found in many commonly consumed foods, has been reported to induce cancers in animals and humans. Several models have been developed to study multistage carcinogenesis in rat liver; these include the Solt-Farber-resistant hepatocyte model. In the Solt-Farber model, the initiation consists of either a necrogenic dose of a hepatocarcinogen or a non-necrogenic dose in conjunction with partial hepatectomy (PH). We report a novel protocol for tumor induction in liver which eliminates the need for PH. Male Wistar rats were injected with single i.p. dose of DEN (200 mg/kg body weight), controls received saline only. After 1 week of recovery, the DEN-treated animals were administered with the repeated doses of 2-acetyamino fluorine (150 mg/kg body weight) orally in 1 % carboxymethyl cellulose that served as promoting agent. Thirty days after the DEN administration, hepatocellular damage was observed as evident by histopathological analysis. The marker enzyme analysis showed elevated levels of serum AST, ALT, and alkaline phosphatase and a decrease in the levels of liver superoxide dismutase and catalase. The oxidative stress in liver was confirmed by elevated levels of lipid peroxidation and a decrease in antioxidant parameters.
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PMID:DEN+2-AAF-induced multistep hepatotumorigenesis in Wistar rats: supportive evidence and insights. 2245 51


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