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)

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

Despite the extensive amount of research conducted on mourning doves (Zenaida macroura), no biochemical reference values exist for this species. Our objective, therefore, was to establish base line clinical chemistry reference values for mourning doves to assist with establishing clinical diagnoses. Wild mourning doves were captured 19 March 1996 to 8 August 1996, and 6 February 1998 to 12 May 1998; blood samples were collected from 382 mourning doves. Plasma biochemical values were established for glucose, sodium, potassium, chloride, enzymatic CO2, albumin, total protein, globulin, calcium, phosphorus, cholesterol, magnesium, aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), and uric acid. These reference values are invaluable for determining diagnosis of diseases of the gastrointestinal, hepatic, renal, cardiovascular, musculoskeletal, and endocrine systems.
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PMID:Blood plasma chemistries from wild mourning doves held in captivity. 1094 41

In the present study, effects of enrofloxacin on biochemical, haematological and blood gas parameters were investigated. Changes in laboratory parameters were monitored during the treatment period. Enrofloxacin was administered (5 mg/kg intramuscularly, once daily) to 10 healthy dogs for 14 days. Acidosis and temporary increases in aspartate aminotransferase, indirect bilirubin, sodium, partial pressure of CO2 and mean corpuscular volume levels as well as decreased levels of inorganic phosphorus, ionized calcium, potassium, partial pressure of O2 and standard bicarbonate were observed. The results of this study suggest that these observed effects of enrofloxacin on blood gas parameters should be taken into consideration in long-term use of the drug.
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PMID:Investigation of biochemical and haematological side-effects of enrofloxacin in dogs. 1151 13

Blood samples were collected from 29 juvenile red pacu (Piaractus brachypomus), ornamental freshwater fish, to establish baseline blood chemistry values. Mean (minimum-maximum) values, obtained by automated bichromatic analysis and ion selective electrode analysis, were as follows: sodium, 150.4 (146-159) mmol/L; potassium, 3.93 (2.7-5.0) mmol/L; chloride, 138.7 (128-150) mmol/L; total CO2, 7.5 (6-10) mmol/L; albumin, 0.86 (0.5-1.0) g/dL; lactate dehydrogenase, 237.8 (65-692) IU/L; aspartate aminotransferase, 49.1 (0-125) IU/L; creatinine, 0.31 (0.2-0.4) mg/dL; calcium, 10.80 (9.5-12.5) mg/dL; anion gap, 6.89 (1.2-12.5) mmol/L; and phosphorus, 7.29 (4.1-8.9) mg/dL.
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PMID:Blood chemistry values of juvenile red pacu (Piaractus brachypomus). 1202 15

The metabolism of biogenic amines and blood chemistry of psychiatric patients were investigated. Eighty newly admitted psychiatric patients suffering from schizophrenia, hypomania, mania and paranoid disorder, and matched with fifteen normal subjects were used for the study. Blood was collected and centrifuged, after which serum was extracted. Serum concentrations of biogenic amines, namely epinephrine, norepinephrine, dopamine and serotonin were determined using spectrofluorimetric method. Serum concentration of 5-HIAA, activities of alanine transaminase and aspartate transaminase were determined. The concentrations of serum protein, albumin, Na+, K+, Cl- and CO2 in the psychiatric patients and control subjects were determined using Synchron CX5 automated spectrophotometer. Results of the study showed that the concentrations of serum epinephrine and norepinephrine in the psychiatric patients were significantly increased, while the concentrations of dopamine and serotonin were significantly decreased, as compared with the controls. Serum 5-HIAA levels were significantly elevated in all psychiatric patients compared with the controls. There was a marked elevation of the activities of alanine transaminase and aspartate transaminase in all psychiatric syndromes, with the exception of paranoid disorder, which was reduced. Data of the study indicate that metabolism of biogenic amines and concentrations of serum proteins, enzymes and some electrolytes were significantly affected in psychiatric patients suffering form schizophrenia, hypomania, mania and paranoid disorder.
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PMID:Biogenic amines metabolism and blood chemistry of psychiatric patients. 1451 Jan 2

To investigate whether hypercapnic acidosis, induced by adding CO2 to inspired gas, would be protective effect against ventilator-induced lung injury (VILI), we ventilated 55 normal white rabbits for 6 hr or until PaO2/FIO2 <200 mmHg. Control group (n=15) was ventilated with peak inspiratory pressure (PIP) of 15 cm H2O, positive end-expiratory pressure (PEEP) of 3 cm H2O, an inspiration-to-expiration ratio of 1:2, and an inspired oxygen fraction (FIO2) of 0.40. High pressure hypercapnic group (HPHC; n=20) was ventilated with PIP of 30 cm H2O, PEEP of 0 cm H2O, and FIO2 of 0.40. Carbon dioxide was introduced into the inspiratory limb of the ventilator circuit, as necessary to maintain hypercapnia (PaCO2, 65 to 75 mmHg). High pressure normocapnic group (HPNC; n=20) was ventilated with same setting of HPHC, except normocapnia (PaCO2, 35 to 45 mmHg). Bronchoalveolar lavage fluid (BALF) lactate dehydrogenase, aspartate aminotransferase, interleukin-8 were significantly higher in high pressure ventilator group than control group (p<0.05). Wet weight to dry weight (WW/DW) and histologic scores were significantly higher in high pressure ventilator group than control group (p<0.05). However, there were no significant differences in oxygenation, BALF inflammatory markers, WW/DW and histologic scores between HPHC and HPNC groups. These findings suggest that hypercapnic acidosis at least induced by CO2 insufflation would not be protective effect against VILI in this model.
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PMID:Does hypercapnic acidosis, induced by adding CO2 to inspired gas, have protective effect in a ventilator-induced lung injury? 1622 49

In the pyrimidine biosynthetic pathway, N-carbamyl-L-aspartate (CA-asp) is converted to L-dihydroorotate (DHO) by dihydroorotase (DHOase). The mechanism of this important reaction was probed using primary and secondary 15N and 13C isotope effects on the ring opening of DHO using isotope ratio mass spectrometry (IRMS). The reaction was performed at three different temperatures (25, 37, and 45 degrees C for hamster DHOase; 37, 50, and 60 degrees C for Bacillus caldolyticus), and the product CA-asp was purified for analysis. The primary and secondary kinetic isotope effects for the ring opening of the DHO were determined from analysis of the N and C of the carbamyl group after hydrolysis. In addition, the beta-carboxyl of the residual aspartate was liberated enzymatically by transamination to oxaloacetate with aspartate aminotransferase and then decarboxylation with oxaloacetate decarboxylase. The 13C/12C ratio from the released CO2 was determined by IRMS, yielding a second primary isotope effect. The primary and secondary isotope effects for the reaction catalyzed by DHOase showed little variation between enzymes or temperatures, the primary 13C and 15N isotope effects being approximately 1% on average, while the secondary 13C isotope effect is negligible or very slightly normal (>1.0000). These data indicate that the chemistry is at least partially rate-limiting while the secondary isotope effects suggest that the transition state may have lost some bending and torsional modes leading to a slight lessening of bond stiffness at the carbonyl carbon of the amide of CA-asp. The equilibrium isotope effects for DHO --> CA-asp have also been measured (secondary 13K(eq) = 1.0028 +/- 0.0002, primary 13K(eq) = 1.0053 +/- 0.0003, primary 15K(eq) = 1.0027 +/- 0.0003). Using these equilibrium isotope effects, the kinetic isotope effects for the physiological reaction (CA-asp --> DHO) have been calculated. These values indicate that the carbon of the amide group is more stiffly bonded in DHO while the slightly lesser, but still normal, values of the primary kinetic isotope effect show that the chemistry remains at least partially rate-limiting for the physiological reaction. It appears that the ring opening and closing is the slow step of the reaction.
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PMID:13C and 15N isotope effects for conversion of L-dihydroorotate to N-carbamyl-L-aspartate using dihydroorotase from hamster and Bacillus caldolyticus. 1675 3

Florida manatees (Trichechus manatus latirostris) are endangered aquatic mammals living in coastal and riverine waterways of Florida and adjacent states. Serum or plasma biochemical analyses are important tools in evaluating the health of free-ranging and captive manatees. The purpose of this study was to measure diagnostically important analytes in the plasma of healthy manatees and to determine whether there was significant variation with respect to location (free-ranging versus captive), age class (small calves, large calves, subadults, adults), and gender. No significant differences in plasma sodium, potassium, bilirubin, glucose, alanine aminotransferase, or creatine kinase were found among these classes of animals. Compared to free-ranging manatees, captive animals had significantly lower mean concentrations of plasma chloride, phosphate, magnesium, triglycerides, anion gap, and lactate. Captive manatees had significantly higher mean values of total CO2, calcium, urea, creatinine, alkaline phosphatase, gamma-glutamyltransferase, total protein, albumin, and albumin/globulin ratio than did free-ranging animals. Differences in the environments of these two groups, including diet, temperature, salinity, and stress, might account for some of these results. The higher plasma lactate and anion gap concentrations and lower total CO2 concentrations of free-ranging manatees were probably due to greater exertion during capture, but the lack of elevated plasma creatine kinase activity relative to captive animals indicates that there was no serious muscle injury associated with capture. Plasma phosphate decreased and total globulins increased with age. Plasma cholesterol and triglyceride concentrations were highest in small calves. Plasma aspartate aminotransferase was higher in large calves than in adults and subadults, and the albumin/ globulin ratio was higher in subadults than in adults. Plasma total CO2 was higher and chloride was slightly lower in females than in males.
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PMID:Clinical biochemistry in healthy manatees (Trichechus manatus latirostris). 1767 11


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