Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Subclinical intoxication of livestock with Astragalus and Oxytropis species (locoweeds) results in decreased animal feed conversion, reduced weight gains, and reproductive failure. Sensitive diagnostic methods to definitively diagnose and monitor intoxication are needed to minimize these losses and better manage locoweed-infested pastures and rangelands. Sera from cattle grazing locoweed were evaluated for alpha-mannosidase activity, serum biochemical values, electrolytes, and thyroid hormone concentrations. As the cows began to ingest locoweed, the mean serum alpha-mannosidase activities dropped significantly (400.0 microM to 72.5 microM). Changes in other serum chemistry values were less specific; however, individual animals (generally those ingesting more locoweed) had elevated levels of alkaline phosphatase (ALP), aspartate aminotransferase, and lactate dehydrogenase, with decreased serum total protein (5.8 +/- 0.8 g/dl) and albumin (2.3 +/- 0.3 g/dl). Mean serum thyroid concentrations (both T4 and T3) were lower in animals that were ingesting locoweed. The calculated swainsonine dose correlated statistically with serum alpha-mannosidase activity, ALP, albumin, Cl, CO2, and thyroid hormone T3. This correlation suggests that serum alpha-mannosidase activity along with potential changes in ALP, albumin, and thyroid hormone concentrations is a sensitive indicator of locoweed exposure and intoxication. These parameters may also be useful for monitoring intoxication and allowing subclinically affected cattle to be removed from infested areas before irreversible damage occurs.
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PMID:Serum alpha-mannosidase activity and the clinicopathologic alterations of locoweed (Astragalus mollissimus) intoxication in range cattle. 785 27

A beef cow was examined to find the cause of decreasing appetite of 2 weeks' duration. The cow was obese (body condition score, 8 of 9), and multiple fetuses were identified on palpation per rectum. Urinalysis revealed > 160 mg of ketones/dl. Abnormal serum biochemical data included high concentrations of bilirubin, creatinine, sodium, and chloride; low concentrations of total CO2 and calcium; and high activity of aspartate transaminase. Treatment included administration of dextrose solution, i.v.; propylene glycol, PO; and insulin, i.v. and SC. The cow's appetite improved gradually over 8 days of treatment. Concentration of ketone bodies in urine decreased to trace amounts by day 4. The cow was discharged on day 10 and gave birth to twins 4 days after discharge (duration of gestation, 279 days). The clinical history of this cow differed from the history of other cattle with ketosis, but mimicked pregnancy toxemia in ewes. Multiple fetuses have not been implicated as a predisposing factor in severe prepartum ketosis of cows.
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PMID:Severe prepartum ketosis in an obese beef cow. 784 49

The safety of low-flow sevoflurane anesthesia, which produces higher concentrations of toxic compounds, has been questioned. One hundred surgical patients received sevoflurane or isoflurane anesthesia at a total flow rate of 1 L/min. End-tidal CO2 concentrations and inspired and end-tidal anesthetic concentrations were monitored during anesthesia. Pre- and postanesthetic clinical laboratory studies were performed in both groups, and no significant differences were found between groups. In the sevoflurane group, the concentrations of degradation products in the circuit were measured by gas chromatography and the temperature of the CO2 absorbent was also measured. Two degradation products were detected: CF2 = C(CF3-O-CH2F (Compound A) and CH3OCF2CH(CF3)OCH2F (Compound B). The highest measured mean concentration of Compound A was 24.6 +/- 7.2 (13.6-41.3) ppm, and that of Compound B (detected in 12 patients) was 1.5 ppm. In both groups, total bilirubin, direct bilirubin, aspartate aminotransferase, and alanine aminotransferase were increased postoperatively. There was no difference between groups. Low concentrations of Compound A were present in low-flow sevoflurane anesthesia, but no significant differences in clinical laboratory values were observed between low-flow sevoflurane and isoflurane anesthesia.
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PMID:Renal and hepatic function in surgical patients after low-flow sevoflurane or isoflurane anesthesia. 871 97

Positive pressure ventilation with hyperdistention of the lungs (PPVHDL) causes microscopic lung injury in rats and in mice. This study compared lung lavage and serum levels of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatinine phosphokinase (CPK), lung lavage and plasma endothelin-1 (ET-1) concentration, lung tissue ET-1 mRNA expression, angiotensin converting enzyme (ACE) activity of lung homogenates, and histology of the lung structure in control and PPVHDL rats. Rats were anesthetized with pentobarbital. While control rats were breathing spontaneously, the PPVHDL rats were ventilated with a rodent ventilator delivering 30 percent oxygen, a tidal volume of 18.6 +/- 4.5 ml/kg, and a respiratory rate of 55 to 60 per minute. End-tidal CO2 was maintained at 38-40 mm Hg. After seven hours, rats were killed and the lungs were lavaged. Red blood cells were present in the sediment of lavage fluid in PPVHDL rats and their lung structure showed severe congestion, alveolar septa filled with red cells, and extravasation of red blood cells and inflammatory cells into the alveolar space. Lung lavage fluid AST and LDH were significantly higher in the PPVHDL compared with the control group (P < 0.03 and P < 0.001, respectively). Electrophoresis of the lung lavage LDH showed increased peak-5 in the PPVHDL group. Serum LDH, CPK, AST, and potassium concentrations [K]+ were significantly higher in the PPVHDL rats whereas their serum total protein level was significantly lower than the control group (P < 0.001). Electrophoretic patterns of serum and lung lavage protein were similar in both groups indicating a transmural passage of serum protein from the intravascular to the intra-alveolar space. No significant difference was found in lung tissue ET-1 mRNA expression and lung protein concentration between the two groups. Lung ACE activity, in contrast, was significantly lower in PPVHDL rats. This study demonstrated that moderate alveolar hyperdistention caused significant structural lung damage accompanied by decreased ACE activity after seven hours of mechanical ventilation and that elevated lung lavage and serum LDH and AST levels in lung lavage and in serum might be early markers of ventilator-induced lung injury in this rat model.
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PMID:Early markers of ventilator-induced lung injury in rats. 887 62

We evaluated postoperative myocardial enzymes and function associated with cryoablation in 20 patients with Wolff-Parkinson-White syndrome undergoing surgical treatment for a single left-sided accessory conduction pathway. Ten patients underwent endocardial atrial incision with cryoablation using CO2 at -60 degrees C for 120 sec (group A), while the remaining 10 patients did not receive cryoablation (group B). Levels of aspartate aminotransferase (GOT), lactate dehydrogenase (LDH), and creatine kinase (CK-MB) on postoperative days 1, 2, and 3 were higher in patients in group A than in group B (p < 0.05). However, mean values remained low (GOT, 120.5 IU/L; LDH, 1105.1 IU/L; CK-MB, 76.3 IU/L). No electrocardiographic changes were detected. Parameters of cardiac function, including cardiac index, stroke volume index, systemic vascular resistance, and ejection fraction, remained unchanged during the postoperative period in both groups. Furthermore, 201Tl cardiac scintigraphy demonstrated no evidence of myocardial perfusion defects due to cryoablation in group A. In conclusion, myocardial damage induced by cryoablation is very minor and is not associated with any clinical impairment of cardiac function.
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PMID:Postoperative influences of surgical cryoablation for Wolff-Parkinson-White syndrome--a analysis of myocardial enzymes and function. 919 39

Polymerized hemoglobin solutions (Hb-based oxygen carriers; HBOCs) and a second-generation perfluorocarbon (PFC) emulsion (Perflubron) are in clinical trials as temporary oxygen carriers ("blood substitutes"). Plasma and serum samples from patients receiving HBOCs look markedly red, whereas those from patients receiving PFC appear to be lipemic. Because hemolysis and lipemia are well-known interferents in many assays, we examined the effects of these substances on clinical chemistry, immunoassay, therapeutic drug, and coagulation tests. HBOC concentrations up to 50 g/L caused essentially no interference for Na, K, Cl, urea, total CO2, P, uric acid, Mg, creatinine, and glucose values determined by the Hitachi 747 or Vitros 750 analyzers (or both) or for immunoassays of lidocaine, N-acetylprocainamide, procainamide, digoxin, phenytoin, quinidine, or theophylline performed on the Abbott AxSym or TDx. Gentamycin and vancomycin assays on the AxSym exhibited a significant positive and negative interference, respectively. Immunoassays for TSH on the Abbott IMx and for troponin I on the Dade Stratus were unaffected by HBOC at this concentration. Tests for total protein, albumin, LDH, AST, ALT, GGT, amylase, lipase, and cholesterol were significantly affected to various extents at different HBOC concentrations on the Hitachi 747 and Vitros 750. The CK-MB assay on the Stratus exhibited a negative interference at 5 g/L HBOC. HBOC interference in coagulation tests was method-dependent-fibrometer-based methods on the BBL Fibro System were free from interference, but optical-based methods on the MLA 1000C exhibited interferences at 20 g/L HBOC. A 1:20 dilution of the PFC-based oxygen carrier (600 g/L) caused no interference on any of these chemistry or immunoassay tests except for amylase and ammonia on the Vitros 750 and plasma iron on the Hitachi 747.
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PMID:Effect of hemoglobin- and Perflubron-based oxygen carriers on common clinical laboratory tests. 929 68

Exudative diathesis, a condition caused by a selenium (Se)/vitamin E deficiency, was studied in chicks. Trios of chicks that showed clinical signs of exudative diathesis were matched for severity. One was injected subcutaneously with 0.5 mL distilled water, and the other two received 15 microg of Se in 0.5 mL distilled water. A chick fed a diet with supplemental Se also received 0.5 mL distilled water. Blood was collected from three chicks 2 d after injection, and from the other chick, 6 d after injection. After blood was collected, pectoral muscle and bone marrow were collected. Deficient chicks showed varying degrees of necrosis in pectoral muscle, whereas recovering chicks had extensive fibrosis in pectoral muscle. An analysis of blood showed differences in CO2, glucose, Se, glutathione peroxidase, alanine aminotransferase, aspartate aminotransferase, and creatine kinase. Heterophils and monocytes were increased in deficient chicks; lymphocytes, basophils, and hemoglobin decreased. After 6 d of recovery, all of the changes noted above were correcting toward normal. Eosinophils, in contrast, were unaffected by a deficiency, but increased in recovering chicks. It is hypothesized that cytokines associated with the inflammatory response accentuate the clinical signs of exudative diathesis.
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PMID:Changes in blood chemistry, hematology, and histology caused by a selenium/vitamin E deficiency and recovery in chicks. 963 Apr 19

Blood samples from adult male and female Charles River Crl:CD (SD) BR rats were collected at weekly intervals for 4 wk to evaluate the effects of inhalation of an anesthetic dose of carbon dioxide (CO2) or of a carbon dioxide-oxygen mixture (CO2/O2) on hematology, coagulation, and serum biochemistry values. During the first 3 wk of the study, rats were assigned to 1 of 3 groups and were bled from the orbital sinus once weekly. Prior to the blood collection, rats in group 1 were exposed to room air only, rats in group 2 received CO2/O2 (approximately 66%:34% CO2:O2) by inhalation, and rats in group 3 received 100% CO2 by inhalation. In the rats exposed to CO2/O2 or CO2, leukocyte counts, lymphocyte counts, and glucose values were higher, and aspartate aminotransferase, creatine kinase, and calcium values were lower compared with those of rats exposed to room air only. Rats exposed to 100% CO2 had slightly (but statistically significant) lower mean corpuscular hemoglobin concentration when compared with rats exposed only to room air. During week 4, all rats were reassigned to 1 of 2 groups and were bled terminally via closed cardiac puncture following exposure to either CO2/O2 or CO2. Increased lymphocyte counts (males only) and glucose and chloride concentrations were noted for rats exposed to CO2/O2 compared with those exposed to CO2. These alterations reiterate the importance of comparing clinical pathology values to those of concurrent control groups that have experienced blood collection under identical conditions in order to avoid potential errors in the interpretation of data.
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PMID:Effects of carbon dioxide inhalation on hematology, coagulation, and serum clinical chemistry values in rats. 1020 85

Glutamate is believed to be an excitatory amino acid neurotransmitter in the retina. Enzymes for glutamate metabolism, such as glutamate dehydrogenase, ornithine aminotransferase, glutaminase, and aspartate aminotransferase (AAT), exist mainly in the mitochondria. The abnormal increase of intracellular calcium ions in ischemic retinal cells may cause an influx of calcium ions into the mitochondria, subsequently affecting various mitochondrial enzyme activities through the activity of mitochondrial calpain. As AAT has the highest level of activity among enzymes involved in glutamate metabolism, we investigated the change of AAT activity in ischemic and hypoxic rat retinas and the protection against such activity by calpain inhibitors. We used normal RCS (rdy+/rdy+) rats. For the in vivo studies, we clamped the optic nerve of anesthetized rats to induce ischemia. In the in vitro studies, the eye cups were incubated with Locke's solution saturated with 95% N2/5% CO2. The activity of cytosolic AAT (cAAT) was about 20% of total activity, whereas mitochondrial AAT (mAAT) was about 75% in rat retina. Ninety minutes of ischemia or hypoxia caused a 20% decrease in mAAT activity, whereas cAAT activity remained unchanged. To examine the contribution of intracellular calcium ions to the degradation of mAAT, we used Ca2+-free Locke's solution containing 1 mM EGTA, ryanodine (Ca2+ channel blocker), and thapsigargin (Ca2+-ATPase inhibitor). In the present study, thapsigargin in Ca2+-free Locke's solution, but not ryanodine in this solution, was found to prevent AAT degradation. AAT degradation was also prevented by calpain inhibitors (Ca2+-dependent protease inhibitor) such as calpeptin at 1 nM, 10 nM, 0.1 microM, 1 microM and 10 microM, and by calpain inhibitor peptide, but not by other protease inhibitors (10 microM leupeptin, pepstatin, chymostatin). Additionally, we determined the subcellular localization of calpain activity and examined the change of calpain activity in ischemic rat retinas. Our results suggest that decreased activity of mAAT in ischemic and hypoxic rat retinas might be evoked by the degradation by calpain-catalyzed proteolysis in mitochondria.
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PMID:Possible mechanism for the decrease of mitochondrial aspartate aminotransferase activity in ischemic and hypoxic rat retinas. 1039 49

The crystal structures of four inhibitor complexes of dialkylglycine decarboxylase are reported. The enzyme does not undergo a domain closure, as does aspartate aminotransferase, upon inhibitor binding. Two active-site conformations have been observed in previous structures that differ in alkali metal ion content, and two active-site conformations have been shown to coexist in solution when a single type of metal ion is present. There is no indication of coexisting conformers in the structures reported here or in the previously reported structures, and the observed conformation is that expected based on the presence of potassium in the enzyme. Thus, although two active-site conformations coexist in solution, a single conformation, corresponding to the more active enzyme, predominates in the crystal. The structure of 1-aminocyclopropane-1-carboxylate bound in the active site shows the aldimine double bond to the pyridoxal phosphate cofactor to be fully out of the plane of the coenzyme ring, whereas the Calpha-CO2(-) bond lies close to it. This provides an explanation for the observed lack of decarboxylation reactivity with this amino acid. The carboxylate groups of both 1-aminocyclopropane-1-carboxylate and 5'-phosphopyridoxyl-2-methylalanine interact with Ser215 and Arg406 as previously proposed. This demonstrates structurally that alternative binding modes, which constitute substrate inhibition, occur in the decarboxylation half-reaction. The structures of d and l-cycloserine bound to the active-site show that the l-isomer is deprotonated at C(alpha), presumably by Lys272, while the d-isomer is not. This difference explains the approximately 3000-fold greater potency of the l versus the d-isomer as a competitive inhibitor of dialkylglycine decarboxylase.
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PMID:Crystal structures of dialkylglycine decarboxylase inhibitor complexes. 1055 38


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