Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

New evidence is obtained for inhibitory effect of isoniazid on activity of transaminases in prolonged application of the drug. Increase in the isoniazid inhibitory effect on alanine aminotransferase activity was shown to correlate with elevated concentration of Cu2+ in blood serum arising in experimental tuberculosis. Cu2+ and Co2+ caused the increase in the inhibitory effect of isoniazid due to their incorporation into structure of the preparation. The microelements, combined with pyridoxine, inhibited alanine aminotransferase and vice versa activated aspartate aminotransferase.
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PMID:[New aspects of the effect of isoniazid on transaminase activity in tuberculosis]. 66 79

In addition to the normal carboxylation reaction, phosphoenolpyruvate carboxylase from Zea mays catalyzes a HCO3(-)-dependent hydrolysis of phosphoenolpyruvate to pyruvate and Pi. Two independent methods were used to establish this reaction. First, the formation of pyruvate was coupled to lactate dehydrogenase in assay solutions containing high concentrations of L-glutamate and aspartate aminotransferase. Under these conditions, oxalacetic acid produced in the carboxylation reaction was efficiently transaminated, and decarboxylation to form spurious pyruvate was negligible. Second, sequential reduction of oxalacetate and pyruvate was achieved by initially running the reaction in the presence of malate dehydrogenase with NADH in excess over phosphoenolpyruvate. After the reaction was complete, lactate dehydrogenase was added, thus giving a measure of pyruvate concentration. At pH 8.0 in the presence of Mg2+, the rate of phosphoenolpyruvate hydrolysis was 3-7% of the total reaction rate. The hydrolysis reaction catalyzed by phosphoenolpyruvate carboxylase was strongly metal dependent, with rates decreasing in the order Ni2+ greater than Co2+ greater than Mn2+ greater than Mg2+ greater than Ca2+. These results suggest that the active site metal ion binds to the enolate oxygen, thus stabilizing the proposed enolate intermediate. The more stable the enolate, the less reactive it is toward carboxylation and the greater the opportunity for hydrolysis.
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PMID:Hydrolysis of phosphoenolpyruvate catalyzed by phosphoenolpyruvate carboxylase from Zea mays. 163 56

1. An improved procedure is reported for purification of the amine dehydrogenase from methylamine-grown Pseudomonas AM1 which yielded a product homogeneous by sedimentation and disc-electrophoretic analysis, with molecular weight of 133000. 2. The purified enzyme had absorption maxima at 280 and 430nm. On aging, a third peak appeared at 325nm, and the 430nm peak decreased in intensity. This spectrum was independent of pH. 3. Addition of 2.5mm-semicarbazide, phenylhydrazine, hydrazine or hydroxylamine produced modified spectra with maxima respectively at 400, 440, 395 and 425nm. 4. Aerobic addition of methylamine resulted in a bleaching of the 430nm peak and the appearance of a new one at 325nm. This spectral change was retained after removal of the methylamine by dialysis. The original spectrum could be restored on addition of phenazine methosulphate. 5. Addition of borohydride partially inactivated the enzyme and produced spectral changes similar to those observed with methylamine. Pre-treatment with methylamine prevented the inactivation by borohydride. The degree of inactivation could be increased by alternate phenazine methosulphate and borohydride treatments. 6. The addition of methylamine or borohydride each caused shifts in the fluorescence emission maximum from 348 to 380nm. 7. Lineweaver-Burk plots of reciprocal activity against reciprocal concentration of either of the substrates n-butylamine or phenazine methosulphate were consistent with a mechanism that involves interconversion of two free forms of the enzyme by the two substrates. 8. The enzyme, although spectrally modified, was not inactivated by dialysis against diethyldithiocarbamate, and contained about 0.27 g-atom of copper/mol, with small traces of cobalt, iron and zinc. 9. Conventional methods of resolution did not release the prosthetic group. Heat denaturation after treatment of the enzyme with methylamine liberated a yellow chromophore which did not reactivate resolved aspartate aminotransferase, and whose spectral, electrophoretic and fluorescence properties did not agree with any recognizable pyridoxal derivatives. 10. Despite the inconclusive results with the isolated chromophore, the observations on the enzyme suggest that it may contain a pyridoxal derivative bound as a Schiff's base which is converted into the pyridoxamine form on aerobic treatment with methylamine and reconverted into the pyridoxal form with phenazine methosulphate. 11. The copper detected is probably not involved in the enzyme mechanism, since most copper-chelating agents are not inhibitory, and since the enzyme does not react with oxygen.
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PMID:Microbial oxidation of amines. Spectral and kinetic properties of the primary amine dehydrogenase of Pseudomonas AM1. 512 84

We examined sera from 159 patients with ischemic heart disease and hypertension and from 50 apparently healthy control subjects for content of trace elements, cholesterol, triglyceride, and enzymes. Concentrations of copper, cobalt, cholesterol, and triglyceride were increased in all patients, but calcium was decreased in patients with hypertension, acute myocardial ischemia, and acute myocardial infarction. Also accompanying acute myocardial infarction were decreased concentrations of zinc and iron but increases in nickel, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase. Magnesium concentration was lower in patients with acute myocardial ischemia. In acute myocardial infarction, the concentrations of copper, zinc, and iron were higher after 21-30 h (as compared with the values at 0-10 h), by which time concentrations of calcium, magnesium, cobalt, and alanine aminotransferase had decreased. The variation in concentration of trace elements in serum from cases of ischemic heart disease and hypertension corresponds to the severity of the disorder.
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PMID:Trace elements in serum from Pakistani patients with acute and chronic ischemic heart disease and hypertension. 671 25

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug that causes massive centrilobular hepatic necrosis at high doses, leading to death. The objectives of this study were to test our working hypothesis that preplaced cell division and hepatic tissue repair by prior thioacetamide (TA) administration provides protection against APAP-induced lethality and to investigate the underlying mechanism. Male Sprague-Dawley rats were treated with a low dose of TA (50 mg/kg, intraperitoneally [i.p.]) before challenge with a 90% lethal dose (1,800 mg/kg, i.p.) of APAP. This protocol resulted in a 100% protection against the lethal effect of APAP. Because TA caused a 23% decrease of hepatic microsomal cytochromes P-450, the possibility that TA protection may be caused by decreased bioactivation of APAP was examined. A 30% decrease in cytochromes P-450 induced by cobalt chloride failed to provide protection against APAP lethality. Time course of serum enzyme elevations (alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase) indicated that actual infliction of liver injury by APAP peaked between 12 to 24 hours after the administration of APAP, whereas the ultimate outcome of that injury depended on the biological events thereafter. Although liver injury progressed in rats receiving only APAP, it regressed in rats pretreated with TA. Acetaminophen t1/2 was not altered in TA-treated rats, indicating that significant changes in APAP disposition and bioactivation are unlikely. Moreover, hepatic glutathione was decreased to a similar extent regardless of TA pretreatment, suggesting that decreased bioactivation of APAP is unlikely to be the mechanism underlying TA protection. [3H]Thymidine incorporation studies confirmed the expected stimulation of S-phase synthesis, and proliferating cell nuclear antigen studies showed a corresponding stimulation of cell division through accelerated cell cycle progression. Intervention with TA-induced cell division by colchicine antimitosis ended the TA protection in the absence of significant changes in the time course of serum enzyme elevations during the inflictive phase of APAP hepatotoxicity. These studies suggest that hepatocyte division and tissue repair induced by TA facilitate sustained hepatic tissue repair after subsequent APAP-induced liver injury, producing recovery from liver injury and protection against APAP lethality.
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PMID:Stimulated hepatic tissue repair underlies heteroprotection by thioacetamide against acetaminophen-induced lethality. 784 22

Livers can be preserved only for a short period without jeopardizing the transplantation outcome. Heat shock proteins (HSPs) protect against ischemia and reperfusion injury. We studied whether their induction and, in particular, the induction of heme oxygenase 1 (HO-1), improves transplantation survival after an extended time of cold storage. Rats were subjected to heat preconditioning (42 degrees C for 20 minutes). Livers were harvested 24 hours later, preserved in cold University of Wisconsin solution for 44 hours, and transplanted in isogeneic rats (arterialized transplantation). HO-1 was specifically induced and inhibited by cobalt protoporphyrin and tin protoporphyrin, respectively. All animals receiving a graft without preconditioning and subjected to 44 hours of cold preservation died within 3 days, whereas 89% of rats who received a graft exposed to heat survived for 3 weeks (P =.0004). Preconditioning reduced serum aspartate transaminase (AST) and lactate dehydrogenase activities after reperfusion, improved bile flow, and decreased the histologic lesions of reperfusion injury. These significant effects of heat preconditioning were prevented by administration of tin protoporphyrin and could be reproduced by administration of cobalt protoporphyrin. In grafts without preconditioning, only a small fraction (<5%) of hepatocytes were positive with the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) assay, and even less expressed activated caspase 3. Preconditioning tended to reduce the number of positive cells and to stimulate the expression of antiapoptotic Bcl-X(L). In conclusion, heat preconditioning and, specifically, overexpression of HO-1 improve posttransplantation survival and graft function after prolonged cold ischemia preservation. The mechanism underlying these beneficial effects does not appear to be prevention of apoptosis.
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PMID:Extended preservation of rat liver graft by induction of heme oxygenase-1. 1198 58

Seventy-three, 10-week-old, newly weaned Omani goats of three different breeds, namely Dhofari (D), Batinah (B) and Jebel Akhdar (JA) were randomly divided into a control (n=38) and a treated group (n=35) for an experimental period of 10 months. Goats in both groups were fed 150 g/day per head of a pelleted concentrate, based on body weight and their requirements and Rhodes grass hay ad libitum, containing 0.12 and 0.10 mg/kg DM cobalt, respectively. Goats in the treated group also received bi-monthly subcutaneous injections of 2000 microg hydroxycobalamin. In contrast to the treated goats, the control animals of all breeds experienced a severe decrease in their serum vitamin B(12) levels, developed pale mucous membranes, appeared scruffy and two breeds (D and B) had significantly lower weight gains from month 5. Untreated kids of all breeds had significant decreases in their red blood cell counts and erythrocyte indices after approximately four months. Controls developed low total serum protein levels whilst activities of alkaline phosphatase and aspartate aminotransferase significantly increased. Although it is widely assumed that goats are more resistant to cobalt deficiency than sheep this is apparently not true for Omani goats. Based on experimental data from previously reported studies and those from the present study it can be concluded that the reduction in weight gains in D and B goats is related to their lower digestibility coefficients for dry matter, crude protein and energy while the increase in alkaline phosphatase and aspartate aminotransferase are associated with developing hepatic lipidosis.
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PMID:Effects of low concentrations of dietary cobalt on liveweight gains, haematology, serum vitamin B(12) and biochemistry of Omani goats. 1632 57

We have examined the protective effect and mechanisms of heme oxygenase-1 (HO-1) induction in rat liver model of ex vivo cold ischemia preservation using cobalt protoporphyrin (CoPP) as HO-1 inducer and zinc protoporphyrin (ZnPP) as HO-1 inhibitor. There was a decrease in both aspartate transaminase and lactate dehydrogenase activities and in malondialdehyde level in liver of the CoPP-treated group compared with controls (p < 0.05). In the CoPP-treated rats, the histological signs of reperfusion injury were much lower than in control. Up-regulation of HO-1 expression was also associated with reduced levels of tumor necrosis factor alpha and interleukin-6. Markedly fewer apoptotic liver cells (determined by TUNEL assay) could be detected in CoPP-treated group compared with the control group. These protective effects were prevented by administration of ZnPP. In conclusion, induction of HO-1 provides protection against liver injury during cold ischemia preservation and improves the preservation of liver graft. The mechanisms underlying these beneficial effects include reduction of oxidative injury and of inflammatory response and prevention of apoptosis.
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PMID:Induction of heme oxygenase-1 improves cold preservation effect of liver graft. 1757 9

Ischemia -modified albumin was regarded as an early marker of cardiac ischemia. On the other hand, it has been reported that increased ischemia-modified albumin levels are associated with unstable plaque processes like percutaneous coronary intervention, acute coronary syndrome or myocardial infarction. This prospective study aimed to investigate the role of ischemia-modified albumin in patients with peripheral vascular disease undergoing peripheral vascular intervention, a plaque-altering procedure without evidence of tissue ischemia. Peripheral vascular intervention was performed in 21 consecutive patients (68.2+/-13.3 years) with typical leg claudication and documented peripheral vascular disease. Additionally, 96 consecutive patients (66+/-12.0 years) undergoing routine exercise stress test for the exclusion of functionally relevant coronary artery disease were defined as controls. It was assumed that in the latter patients no unstable plaque-altering processes were present. Blood samples were drawn before, and 30 min and 3 h after, revascularization in the peripheral vascular intervention group, as well as before, and 30 min and 3 h after, maximum stress testing in the control group, respectively. Ischemia-modified albumin levels were analyzed using the albumin cobalt-binding test. In patients undergoing peripheral vascular intervention, ischemia-modified albumin increased from 116.6+/-19.1 U/ml at baseline to 132.0+/-19.3 U/ml 30 min after intervention (+14.4+/-15.7%, P<0.001) and decreased to 123.5+/-17.8 U/ml 3 h later (-5.7+/-10.5%, P<0.001 compared with postintervention, P<0.001 compared with baseline). The control group showed a slight but significant decrease in ischemia-modified albumin from 103.0+/-11.0 to 100.2+/-11.6 U/ml poststress (-2.2+/-11.5%, P<0.05) and returned close to baseline 3 h later (101.8+/-10.3 U/ml, +2.4+/-10.9%, P=NS, compared with poststress and with baseline). For both groups, ischemia-modified albumin showed no correlation with albumin (at baseline P=0.62) and total protein (P=0.67), but significant correlation with creatinine (P=0.04) and C-reactive protein (P=0.02). In addition, ischemia-modified albumin was independent of age, sex, alanine aminotransferase, aspartate aminotransferase, creatine kinase, creatine kinase-MB, cholesterol, and triglycerides. This study showed an increased basal ischemia-modified albumin level in patients with peripheral vascular disease undergoing peripheral vascular intervention. Ischemia-modified albumin levels transiently increased shortly after peripheral vascular intervention, indicating a strong correlation between serum concentration of ischemia-modified albumin and processes associated with acute plaque disruption/rupture.
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PMID:Effects of peripheral vascular intervention on ischemia-modified albumin. 1762 87

Vitamin B(12) contains a cobalt complex and accumulates at high levels in the liver. Vitamin B(12) was examined for its hepatoprotective effect on dimethylnitrosamine-induced liver injury in mice. Vitamin B(12) decreased the blood levels of aspartate aminotransferase and alanine aminotransferase, and clearly inhibited the overaccumulation of collagen fibrils. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of the liver showed that the gene expression of alpha-smooth muscle actin and heat-shock protein 47, which are markers of fibrosis, were suppressed by vitamin B(12) administration. Our findings indicate that vitamin B(12) could be an effective hepatoprotective agent.
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PMID:Hepatoprotective effect of vitamin B12 on dimethylnitrosamine-induced liver injury. 1823 93


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