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)

Molecular modeling suggested that the large and small domain of mitochondrial aspartate aminotransferase might be linked by an engineered disulfide bond that could be expected to interfere with ligand-induced and syncatalytic changes in conformation and thus to assist in the elucidation of their significance for the catalytic mechanism. His-352, which is situated in the small domain close to Cys-166 of the large domain, was replaced with a cysteine residue by oligonucleotide-directed mutagenesis. Aspartate aminotransferase H352C, that had not been exposed to reducing conditions, in part contained a disulfide bond between Cys-166 and Cys-352. Exposure to a reducing agent cleaved the crosslink completely and produced an enzyme derivative with 8% of the activity of the wild type enzyme. Cu2+-mediated autoxidation resulted in complete formation of the disulfide bond and a decrease in enzymic activity to 2%. Independently of the redox state of the disulfide bond, the H352C substitution seems to shift the equilibrium from the open toward the closed conformation of the enzyme. This change in conformation was accompanied by an increase in the binding affinity for both the amino and oxo acid substrate by one order of magnitude. Apparently, 1-2 kcal/mol of the binding energy of the substrates are no longer diverted to shift the conformational equilibrium toward the closed conformation. The kcat/Km values were unchanged or even increased in the reduced form of the mutant enzyme and only slightly decreased in its oxidized form. Both the disulfide-independent decrease in enzymic activity, as observed in reduced aspartate aminotransferase H352C and also in two other mutant enzymes (C166H/H352C and H352Q), and the redox-dependent modulation of activity indicate that unhindered domain movements are essential for full catalytic competence of aspartate aminotransferase.
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PMID:Modulation of the activity of mitochondrial aspartate aminotransferase H352C by the redox state of the engineered interdomain disulfide bond. 792 41

In order to assess the liver protective activity and the antioxidant properties of a new silybin complex (IdB1016), we carried out a short-term pilot study on 20 patients with chronic active hepatitis (CAH), randomly assigned to 240 mg of silybin b.i.d. (10 patients, 4 m/6 f, mean age: 50 years) or placebo (10 patients, 2 m/8 f, mean age: 55 years). Blood samples were collected before and after 7 days of treatment for liver function tests (LFTs), malonaldehyde (MDA) as an index of lipid peroxidation, and copper (Cu) and zinc (Zn), two trace elements involved in protecting cells against free radical-mediated lipid peroxidation. In the treated group, there was a statistically significant reduction of mean (+/- SEM) serum concentrations of aspartate aminotransferase (AST) from 88.0 (+/- 13.3) to 65.9 (+/- 7.5) u/l, (p < 0.01), of alanine aminotransferase (ALT) from 115.9 (+/- 12.9) to 82.5 (+/- 10.6) u/l (p < 0.01), of gamma-glutamyltranspeptidase (gamma-GT) from 51.4 (+/- 9.3) to 41.3 (+/- 4.2) u/l (p < 0.02) and of total bilirubin (TB) from 0.76 (+/- 0.08) to 0.53 (+/- 0.04) mg/dl (p < 0.05). Alkaline phosphatase (AP) fell slightly from 143.4 (+/- 6.4) to 137.5 (+/- 7.8) u/l. There were no significant changes in MDA, Cu or Zn serum concentrations. These results show that IdB1016 may improve LFTs related to hepatocellular necrosis and/or increases membrane permeability in patients affected by CAH.
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PMID:A pilot study on the liver protective effect of silybin-phosphatidylcholine complex (IdB1016) in chronic active hepatitis. 822 95

The rat liver rhodanese (thiosulphate: cyanide sulfurtransferase EC 2.6.1.1) has been immobilized on polyacrylamide gels. The immobilized enzyme had a pH optimum of 7.4 and Km values of 3.25 mM and 1.12 mM for S2O3(2-) and KCN, respectively. The enzyme was competitively inhibited by NaNO2 and CH3COONa and noncompetitively by amyl-nitrite. A modulation of activity was observed in the presence of Ca2+, Zn2+, and Cu2+. The results are discussed in line with the detoxicating function of liver rhodanese.
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PMID:Immobilized rhodanese: some aspects of anion inhibition kinetics and modulation by cations. 835 60

Several biochemical events accompany and mediate the development of chronic liver disease and its evolution into cancer. Low plasma zinc and high copper levels have been observed in various liver diseases, such as liver cirrhosis and viral hepatitis, while increased oestradiol levels have been documented in chronic liver damage and hepatocellular carcinoma. We administered CCL4 intragastrically to 10 female Sprague Dawley rats for 30 weeks. All animals developed cirrhosis and four also developed hepatocellular carcinoma. Plasma levels of zinc, copper and oestradiol were significantly higher in the latter group than in animals with simple cirrhosis. Progesterone, AST and bilirubin showed a trend toward significant differences whereas testosterone and ALP levels were unchanged. These findings add to the evidence that sex hormones and trace elements are involved in the process of the development of chronic liver damage and carcinogenesis.
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PMID:Sex hormones and trace elements in rat CCL4-induced cirrhosis and hepatocellular carcinoma. 835 89

1. Over an 8-year period, 19 biochemical parameters have been determined at various ages in the blood serum of 92 clinically healthy Lechwe waterbucks (Kobus leche), 33 males and 59 females. 2. Significant differences have been noted with age. In neonates, the lowest values of total proteins, glucose, creatinine, urea, AST, ALT and iron have been noted; the highest ones have been seen for cholesterol, alkaline phosphatase, calcium and phosphorus. 3. With regard to sex, raised values of glucose, urea, alkaline phosphatase and ALT, and lowered values of cholesterol, have been noted in juvenile females compared with males of the same age. 4. In adult females, higher levels of urea and cholesterol and lower levels of glucose, triglycerides and natrium have been recorded compared with males. 5. With sex and age, no significant changes have been found in the levels of GGT, magnesium, chlorides and copper. 6. Our findings are discussed with those abstracted from the literature for related species.
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PMID:Serum chemistry profiles for Lechwe waterbucks (Kobus leche): variations with age and sex. 840 53

Citrullus colocynthis seed was fed at 2% and 10% of the basal diet to 7-d-old Bovans-type chicks for 6 w. Average body weights and efficiency of feed utilization were markedly depressed in the chicks on 10% Citrullus feed, and the serum activities of LDH, AST and CK and concentrations of total lipid and zinc were significantly increased. The concentration of serum total iron binding capacity was particularly reduced in chicks on 2% Citrullus feed. The concentrations of other serum and blood constituents and of hepatic copper, manganese and zinc were not significantly changes. Lesions seen in the intestines, livers, kidneys and other tissues were fully reversed 4 w after removal from the experimental diet.
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PMID:An estimation of Citrullus colocynthis toxicity for chicks. 854 Feb 28

Fischer rats were a fed diet supplied with copper chloride (150-600 ppm) for 60 d from weaning. Serum (glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) activities were increased with the increase of Cu concentration in the diet. Biliary excretion of Cu was related to the dietary Cu level. Depositions of hepatic and renal Cu were also related to the dietary Cu level in a dose-dependent manner. In particular, hepatic (155.2 +/- 13.3 micrograms/g) and renal (44.9 +/- 4.4 micrograms/g) Cu concentrations increased abruptly in the Cu-600 ppm group. In the liver, about 60% of Cu was distributed in the soluble fraction (100,000 g supernatant). In the Cu-600 ppm group, 25% of cystosolic Cu was bound to metallothionein (MT). Our results suggest that chronic exposure to Cu appears to have a deleterious effect on the hepatic function, and further, that even in rats with normal biliary Cu excretion, clearance of Cu from the liver may be marginal when dietary Cu is near the 600-ppm level. Although Cu is an essential nutrient, an overload of Cu should be avoided.
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PMID:Response of hepatic function to hepatic copper deposition in rats fed a diet containing copper. 856 84

The study was performed on 4 groups of male Wistar rats, receiving p.o. through 3 months every day: 1). Sodium nitrite in dose 30 mg/kg b.w. x day (0.2 LD50); 2). Cupric chloride in dose 4.67 mg/kg b.w. x day (0.03 LD50); 3 ). Cupric chloride and sodium nitrite in amounts as above, and 4). Control group--received dest. water. The activity of alanine aminotransferase (AlAT), aspartate aminotransferase (AspAT), gamma-glutamyltransferase (GGTP-ase) and creatinine and urea level in blood plasma were determined 24 hours after the last application of compounds. There was showed, that every day rats' intoxication with sodium nitrate during 90 days caused the significant increase of gamma-glutamyltransferase activity and decrease of urea level in the blood plasma. Subchronic exposure to copper and copper with sodium nitrate causes no effect on biochemical parameters were studied.
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PMID:[Evaluation of the combined effect of cupric chloride and sodium nitrite on selected biochemical parameters in rat plasma (subchronic exposure)]. 861 20

The objective of the paper was to assess the occurrence of congenital struma in kids in relation to the clinical and biochemical finding in their mothers. Observations involved 46 imported goats of Saanen and Alpine breeds in the course of kidding and their kids. Thyroid gland hypertrophy (39 goats) and somewhat worse or even bad state of nutrition were dominant clinical findings in pregnant goats and in goats after kidding. Abortions in the last month of pregnancy were recorded in 14 goats, and 14 goats delivered stillborn kids. Eighteen goats delivered 26 liveborn kids, but 18 out of them died within 12 to 24 hours after birth. Dead kids were hairless, they had skin edema, and very shortened thoracic as well as pelvic limbs. The thyroid gland was well visible and palpable. Surviving kids lagged behind in their growth and often suffered from bronchopneumonia as an additional disease. Iodine concentration in the blood serum of goats (5.58 +/- 2.14 mumol/l) was significantly lower (P < 0.01) in comparison with kids (133.4 +/- 15.61 mumol/l). This state was characterized by adequate T3 and T4 concentrations in the blood serum of goats (1.78 +/- 0.59 and 4.53 +/- 4.44 nmol/l, resp.) and of kids (4.66 +/- 2.26 and 182.93 +/- 2.59 nmol/l, resp.). Iodine content in the thyroid gland of the seven kids that died was 1.86 +/- 0.96 mg/kg fresh tissue. Examination of indicators of the internal environment in the blood serum showed alternate statistical differences (P < 0.01) between adult goats and their kids in erythrocyte counts, hemoglobin, hematocrit value, leucocyte counts, activities of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, concentrations of total protein, albumin, total immunoglobulins, total lipids, cholesterol, phosphorus, copper, iron and zinc, while the explicit relation to disorders of iodine metabolism and thyroid hormones was not confirmed. The average content of iodine in the examined samples of soil (14.67 mg/kg) and alfalfa hay (0.1 mg/kg) demonstrated that primary deficiency of iodine in goats was the cause of congenital struma in kids.
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PMID:[Iodine deficiency in goats as a cause of congenital goiter in kids]. 869 66

We applied a multivariate analysis to a large series of serum biochemical tests in an attempt to identify a function that could efficiently discriminate cirrhosis from hepatocellular carcinoma (HC). We analyzed two successive temporal cohorts (1987-90; 1991-94) of HC and cirrhotic patients, all histologically classified (first cohort: 69 cirrhosis and 39 HC; second cohort: 66 cirrhosis and 38 HC). Using data from the first temporal cohort of patients, we obtained a discriminant function based on seven serum analytes: alpha-fetoprotein, the hepatic isoenzyme of alkaline phosphatase, lactate dehydrogenase isoenzyme 5, total gamma-glutamyltransferase (GGT), GGT isoforms complexed with low-density lipoprotein, aspartate aminotransferase, and copper. The same panel of analytes emerged when the second cohort was tested and also when both cohorts were tested together. In the two successive cohorts (total, 212 patients) with a prevalence of cirrhosis vs HC of approximately 2:1, the discriminant function correctly classified 93% of cases, the highest percentage of correct classification of the two diseases obtained so far by laboratory approaches. Validation with the jackknife reallocation statistical algorithm confirmed these results. In addition, of six patients with liver cirrhosis for whom we had the opportunity of following up and observing the evolution to HC, five were classified as HC at diagnosis by the multivariate discriminant analysis; i.e., discriminant analysis provided a diagnostic lead time of 6-12 months over histology. This discriminant function, based on easy-to-perform serum biochemical tests, may help solve a fundamental problem of differential diagnosis in the evolution of chronic liver diseases from cirrhosis to HC.
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PMID:Differential diagnosis between hepatocellular carcinoma and cirrhosis through a discriminant function based on results for serum analytes. 869 87


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