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)

1. The concentration of HCO3- (independent of any change of pH) exerts different effects on glutamine metabolism in rat kidney-cortex tubules, hepatocytes and enterocytes.2. In kidney tubules HCO3- (10.5-50 MM) has no effect on glutaminase (EC 3.5.1.2), whereas glutamate dehydrogenase (EC 1.4.1.3) is inhibited as HCO3- concentration is increased. The result is that flux through the entire glutamate-to-glucose pathway is inhibited by increasing HCO3- concentrations. A large proportion (more than 30%) of the glutamine removed undergoes complete oxidation. 3. In hepatocytes, and to a smaller extent in enterocytes, HCO3- is an accelerator of glutaminase. Synthesis of glucose and urea from glutamine in hepatocytes increases as HCO3- concentration is increased. Calculations show that fumarate, formed via aspartate aminotransferase and arginino-succinate lyase, is the precursor of the glucose. There is no complete oxidation of the carbon skeleton of glutamine in hepatocytes. 4. Leucine at near-physiological concentrations (0.1-1 mM) is an accelerator of glutaminase in hepatocytes, but not in kidney tubules or in enterocytes. 5. The results are discussed in relation to regulation of acid/base balance in vivo.
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PMID:A role for bicarbonate in the regulation of mammalian glutamine metabolism. 54 52

1. Bicarbonate stimulates the activity of rat brain cytoplasmic and mitochondrial alanine aminotransferase (EC 2.6.1.2) probably due to the enhanced affinity for its substrates. 2. Under the same conditions, the activity of crystalline aspartate aminotransferase was inhibited. 3. The role of bicarbonate buffer in regulation of alanine aminotransferase activity and synthesis of alanine are discussed.
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PMID:Effect of bicarbonate buffer on the activity of cytoplasmic and mitochondrial alanine aminotransferase. 117 9

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

A 3-year-old mare repeatedly had clinical signs of rhabdomyolysis on mild exertion. Serum creatine kinase and aspartate transaminase activities were high at rest. Responses to dietary sodium bicarbonate were tested through 7 alternating periods of supplementation of a basal ration of timothy hay and oats. Physical signs; venous blood pH and gases; blood glucose and lactate; serum electrolytes, enzymes, and creatinine; and urine pH were monitored before and after exercise. Dietary sodium bicarbonate raised resting venous blood pH and bicarbonate slightly and significantly increased urine pH from pH 7.46 to 8.2 (P less than 0.001). An exercise test included 5 minutes at the walk followed by 20 minutes at the trot. The exercise induced gait stiffness, muscle fasciculations, and muscle induration when the diet was not supplemented, but not when it was supplemented with sodium bicarbonate. Myoglobin was present in 16 of 21 urine samples after exercise during nonsupplemented periods, but only in 3 of 28 urine samples during supplemented periods (P less than 0.0001). Bicarbonate supplementation significantly decreased the responses of blood lactic acid, serum creatine kinase, and aspartate transaminase to exercise. Supplementation of the diet was associated with higher venous blood pH and bicarbonate ion concentrations throughout exercise. Dietary sodium bicarbonate apparently mitigated or prevented physical, chemical, and enzymatic characteristics of exertional rhabdomyolysis in this mare, possibly through its enhancement of buffering capacity in muscle tissue fluids.
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PMID:Dietary sodium bicarbonate as a treatment for exertional rhabdomyolysis in a horse. 300 12

The hepatotoxicity of a new erythromycin derivative, erythromycin acistrate (EA, 2'-acetyl erythromycin stearate), was compared with that of erythromycin stearate (ES), erythromycin estolate (EE) and erythromycin-11,12 cyclic carbonate (EC) in 4-5-day, 28-day and 6-month oral toxicity studies in rats and dogs. In the 4-day rat study, EC caused fatty metamorphosis in the liver. ES caused similar, but milder changes at a dose nearly five times higher. The 5-day dog study revealed markedly increased serum alanine aminotransferase (S-ALAT), serum aspartate aminotransferase (S-ASAT), serum alkaline phosphatase (S-APHOS) and serum gamma-glutamyl transpeptidase (S-gamma-GT) values in the EC- and EE-groups, and slightly elevated S-ALAT values also in the EA- and ES-groups. Microscopy revealed cholangitis, pericholangitis and phlebitis in the portal areas in the EC-group at all doses. Epithelial hyperplasia was observed also in the bile ducts. EE caused similar but milder changes. The changes in the EA-group were small, but mildly atypical bile duct epithelium was seen in female dogs receiving 2 x 200 mg/kg of EA. The ES-group was practically without changes and very much like the EA-group. Thus the dog proved to be a more sensitive model for assessing the hepatotoxicity of erythromycin derivatives. In the 28-day studies, only EA and ES were investigated. In the rat study, slightly elevated serum enzyme levels within the normal range were measured in the high-dose regimens of both drugs. In the dog study, 300 mg/kg of EA caused slightly elevated S-ALAT in males, but the values returned to normal after a 2-week off-dose period. Only EA was studied in the 6-month study. In male rats, 400 mg/kg of EA caused slightly elevated enzyme levels and neutral fat droplets in centrilobular hepatocytes. In male dogs given 150 mg/kg of EA, S-ALAT, S-APHOS, and S-gamma-GT values were elevated after four weeks of treatment but returned to normal thereafter. No severe changes were seen in the liver histopathology. In conclusion, EC and EE were clearly hepatotoxic in dogs, and EC also in rats. EA, and to a somewhat lesser extent ES, showed signs of mild hepatotoxicity only at high doses. This evidently reversible effect was considered a common characteristic of erythromycins.
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PMID:Comparative liver toxicity of various erythromycin derivatives in animals. 233 25

In a double-blind trial, 327 patients (57 men) over 65 (mean age 79.5) years received all possible combinations of calcium carbonate 3 g, vitamin D3 1000 iu, methandienone 2.5 mg and/or placebos daily for 9 months. The higher incidence of bone fractures in the placebo group was not significant. Serum calcium, phosphorus, creatinine, aspartate aminotransferase and alkaline phosphatase were followed: the greatest changes occurred with methandienone, which thus reduced osteoporotic activity and increased the muscular mass most effectively; calcium carbonate had the poorest effect. Surprisingly, coronary mortality was higher among those taking all three active substances. With two treatments the increase was not significant, but when both the groups receiving a combination of any two of the treatments were compared with those taking only one or neither of these two treatments, a significant increase in coronary deaths was seen, most significant (P less than 0.001) in those receiving vitamin D3 and methandienone.
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PMID:Calcium, vitamin D and anabolic steroid in treatment of aged bones: double-blind placebo-controlled long-term clinical trial. 634 29

Extremely high bicarbonate (HCO3-) and anion gap values were measured in two horses and a calf using the Hitachi 911 automated serum biochemistry analyzer. All three animals had severe muscle disease as evidenced by markedly increased aspartate aminotransferase and creatine kinase activities. Laboratory error was suspected as the source of the increased HCO3- because values calculated from blood gas analysis were normal. It was hypothesized that increased serum lactate dehydrogenase (LDH) activity and pyruvate concentration overwhelmed the oxamate LDH inhibitor in the enzymatic HCO3- assay, resulting in consumption of NADH and falsely elevated spectrophotometric reading. Serum LDH activity was markedly increased in all three patients. In an attempt to reproduce this interference in vitro, LDH and pyruvate were added to normal bovine serum. Bicarbonate concentration was artifactually increased in a linear, dose-response relationship proportional to the amount of LDH activity in the sample; addition of pyruvate augmented this increase. It was concluded that increased serum LDH activity and pyruvate concentration secondary to severe muscle disease can result in artifactual increases in serum HCO3- values obtained by routine enzymatic assay.
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PMID:Artifactually increased serum bicarbonate values in two horses and a calf with severe rhabdomyolysis. 1207 44

The effect of heat stress on changes in milk production, rectal temperature, respiratory rate and blood chemistry was evaluated in three groups of six mature Holstein, Jersey and Australian Milking Zebu (AMZ) dairy cows. These animals were subjected to a cool environment when the mean temperature-humidity index (THI) was 72+/-1.4 (dry bulb temperature of 22.2-24.4 degrees C and relative humidity of 100-60%) during the month of December. This experiment was repeated during the hotter month of July of the following year, when the mean THI was 93+/-3.1 (dry bulb temperature of 35.6-43.9 degrees C and relative humidity 95-35%). Holstein cows produced more (p <0.01) milk than AMZ and Jersey cows during the cooler months of the year and all the cows were dry during the hotter months from June until September. Heat stress increased (p<0.01) rectal temperature and respiratory rate in all three breeds. Heat stress had no effect on blood pH in Holstein and AMZ cows but lowered (p <0.01) blood pH from 7.42 to 7.34 in Jersey cows. In addition, heat stress lowered (p <0.01) blood pCO2 (kPa), bicarbonate (HCO3, mmol/L), base excess (BE, mmol/L) and plasma chloride (Cl-, mmol/L) in all three breeds. The total haemoglobin (THb, g/dl) was elevated (p <0.01) in all three breeds when they were subjected to heat stress. Heat stress increased (p<0.01) oxygen saturation (O2SAT, %) in Jersey and AMZ cows but lowered it (p <0.01) in Holstein cows. On the other hand, heat stress increased (p <0.01)pO2 (kPa) in Holstein and Jersey cows but lowered it (p <0.01) in AMZ cows. Heat stress increased (p <0.01) plasma potassium (K, mmol/L) and calcium (Ca, mmol/L) only in Holstein and Jersey cows but lowered them (p<0.01) in AMZ cows. The plasma glucose (GLU, mmol/L) increased (p<0.01) with heat stress in Holstein and AMZ cows but decreased (p <0.01) in Jersey cows. Heat stress increased (p<0.01) plasma creatinine (CR, (mol/L) but lowered (p<0.01) plasma creatinine phosphokinase (CPK, IU/L), aspartate aminotransferase (AST, IU/L) and blood urea nitrogen (BUN, mmol/L) in all three breeds. These results indicate that heat-stressed Holstein and AMZ cows were able to maintain their acid-base balance with a marginal change in their pH of 0.02 when their rectal temperatures increased by 0.47 and 0.38 degrees C, respectively. When heat stress increased the rectal temperature in Jersey cows by 0.70 degrees C, the pH decreased (p<0.01) from 7.42 to 7.34. However, even with this decrease 0.08 the pH is still within the lower physiological limit of 7.31.
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PMID:Effect of heat stress on milk production, rectal temperature, respiratory rate and blood chemistry in Holstein, Jersey and Australian Milking Zebu cows. 1556 29

Stingrays are prominent marine animals; however, there are few published reference values for their blood chemistry and hematology. Twenty-eight southern stingrays (Dasyatis americana) were caught using the bottom trawl nets of fishery-independent boats operated by the South Carolina Department of Natural Resources during June and July 2002 from Winyah Bay, South Carolina, to St. Augustine, Florida. Median values of blood and plasma obtained from live animals promptly after capture are as follows: packed cell volume = 0.22 L/L (22%), total solids (TS) = 56.5 g/L (5.65 g/dl), total protein (TP) = 26 g/L (2.6 g/dl), sodium = 315 mmol/L, potassium = 4.95 mmol/L, chloride = 342 mmol/L, calcium = 4.12 mmol/L (16.5 mg/dl), phosphorus = 1.5 mmol/L (4.7 mg/dl), urea nitrogen = 444 mmol/L (1,243 mg/dl), glucose = 1.69 mmol/L (30 mg/dl), aspartate aminotransferase = 14.5 U/L, creatine phosphokinase = 80.5 U/L, osmolality = 1065 mOsm/kg, and lactate = 3.1 mmol/L. Bicarbonate was less than the low end of the instrument range (5 mmol/L) in all but three samples. Anion gap was negative in all samples. Albumin was less than the low end of the instrument range (1 g/dl) in all except one sample. Osmolality was significantly higher in the rays caught in the southern region. TS and TP values were linearly related to each other, and the equation for the fitted line is TS = (11.61 x TP) + 25.4 (in g/L) [or TS = (1.161 x TP) + 2.54 (in g/dl)]. The reference ranges reported in this study can be used to aid in the management of aquarium stingrays and to create a baseline for health monitoring of the wild Dasyatis spp.
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PMID:Plasma biochemistry reference values of wild-caught southern stingrays (Dasyatis americana). 1573 87

Monthly variations in serum chemistry of the American lobster, Homarus americanus Milne-Edwards, were investigated at one location in Long Island Sound (LIS). Comparisons between three locations within and outside LIS were also made for a single time point. Most serum analytes displayed significant fluctuation over the study period and between locations. Temporal patterns could be classified as: low in cool months/high in warm months, i.e. Na, Cl, Na:K ratio, Ca, albumin:globulin ratio, percentage Fe saturation; high in cool months/low in warm months, i.e. pH, K, urea, total protein, albumin, globulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipaemia; June spike, i.e. glucose, cholesterol, creatine kinase, iron, transferrin iron-binding capacity; other less obvious fluctuations, i.e. Mg, PO4; and no apparent fluctuation, i.e. HCO3, alkaline phosphatase. The proportion of samples correctly classified into month of collection by a subset of 13 analytes using discriminant analysis improved as the months progressed from May (0.75) to October (>0.95). Discriminant analysis also resolved 96.5% of samples by location. The significant depression of serum calcium at the eastern LIS site correlates with excretory calcinosis, a calcium storage disease described from lobsters at this site, but contrasts with a seasonal elevation in serum calcium recorded in the temporal component of the study. Serum proteins, the electrolytes Ca and K and the enzymes ALT and AST proved to have the strongest spatio-temporal patterns of variation. Serum chemistry is a useful research tool for lobster populations, but the dearth of information on the homology of analyte functions in this species with those in vertebrate species makes interpretation of the results challenging. Late summer/autumn water conditions appear to cause stress for lobsters in LIS.
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PMID:Spatio-temporal variation in serum chemistry of the lobster, Homarus americanus Milne-Edwards. 1630 28


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