Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The RS-isomers of beta-mercapto-alpha-ketoglutarate, beta-methylmercapto-alpha-ketoglutarate and beta-methylmercapto-alpha-hydroxyglutarate have been synthesized. Beta-Mercapto-alpha-ketoglutarate was a potent inhibitor, competitive with isocitrate and noncompetitive with NADP+, of the mitochondrial NADP-specific isozyme from pig heart (Ki = 5 nM; Km (DL-isocitrate)/Ki(RS-beta-mercapto-alpha-ketoglutarate) = 650) and pig liver, the cytosolic isozyme from pig liver (I0.5 = 23 nM), and the NADP-linked enzymes from yeast (Ki = 58 nM) and Escherichia coli (Ki = 58 nM) at pH 7.4 and with Mg2+ as activator. beta-Mercapto-alpha-ketoglutarate was also an effective inhibitor of NADP-isocitrate-dehydrogenase activity in intact liver mitochondria. beta-Mercapto-alpha-ketoglutarate was a much less potent inhibitor for heart NAD-isocitrate dehydrogenase (Ki = 520 nM) than for the NADP-specific enzyme. beta-Methylmercapto-alpha-ketoglutarate (I0.5 = 10 microM) was a much less effective inhibitor than the beta-mercapto derivative for heart NADP-isocitrate dehydrogenase. The beta-sulfur substituted alpha-ketoglutarates were substrates for the oxidation of NADPH by heart NADP-isocitrate dehydrogenase without requiring CO2. beta-Methylmercapto-alpha-hydroxyglutarate, the expected product of reduction of beta-methylmercapto-alpha-ketoglutarate, did not cause reduction of NADP+ but it was an inhibitor competitive with isocitrate for NADP-isocitrate dehydrogenase. The beta-sulfur substituted alpha-ketoglutarate derivatives were alternate substrates for alpha-ketoglutarate dehydrogenase and the cytosolic and mitochondrial isozymes of heart aspartate aminotransferase but had no effect on glutamate dehydrogenase or alanine aminotransferase.
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PMID:beta-Sulfur substituted alpha-ketoglutarates as inhibitors and alternate substrates for isocitrate dehydrogenases and certain other enzymes. 394 94

The effects of a homologous series of fatty acids with a chain length of two to eight on the rate of pyruvate oxidation and covalent interconversions of the pyruvate dehydrogenase complex (PDH) were studied in isolated perfused rat hearts. In the Langendorff-perfused heart beating at 5 Hz against an aortic pressure of 59 mmHg (7.85 kPa), a positive linear correlation was found between the fraction of PDH existing in the active non-phosphorylated form of pyruvate dehydrogenase complex (PDHa) and the pyruvate oxidation rate until the PDHa fraction increased to 48%. This value resulted in a saturation of the citric acid cycle and further activation did not increase the metabolic flux. The PDHa content of the tissue was higher during infusion of odd carbon number fatty acids than during infusion of even carbon number fatty acids. Propionate caused an almost maximal (93%) activation of PDH. A negative correlation was found between the mitochondrial NADH/NAD+ ratio and the PDHa content. A negative correlation was also found between the acetyl-CoA/CoA ratio and the tissue PDHa content. The rate of labelled CO2 production, the specific radioactivity of tissue alanine and the metabolic balance sheet demonstrated that the alanine aminotransferase reaction in the total tissue does not reach equilibrium with the mitochondrial pyruvate pool during propionate oxidation, but the equilibrium is reached during the oxidation of even-number carbon fatty acids. This suggests that pyruvate is formed from propionate-derived metabolites also in the cytosol, although the primary metabolism of propionate occurs in the mitochondria. The results indicate that the rate of pyruvate oxidation in the myocardium is mainly regulated by covalent interconversion of PDH. During propionate oxidation the PDHa content in the tissue can increase beyond the point of saturation of the citric acid cycle and this indicates that feedback inhibition of the enzyme is rate-determining under these conditions.
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PMID:Regulation of pyruvate dehydrogenase during infusion of fatty acids of varying chain lengths in the perfused rat heart. 408 5

Fasted male rats were given six doses of 14CCl4 ranging from non-hepatotoxic (0.1 mmole/kg) to severely hepatotoxic (26 mmoles/kg). Time-course and pharmacokinetics of CCl4, 14CO2 and CHCl3 elimination by exhalation were monitored by measuring amounts recovered in breath during discrete 15-min intervals for 8-12 hr. Amounts of 14C-labeled metabolite recovered bound to liver macromolecules at 24 hr and excreted in urine or feces for 24 hr were also determined. Comparison pharmacokinetic studies were done with 14CHCl3 and Na(2)14CO3. After all doses of 14CCl4, the major metabolite was CO2, twenty to thirty times less metabolite was recovered bound to liver macromolecules, and intermediate amounts of metabolite were excreted in urine and feces. CHCl3 was the least abundant metabolite at low CCl4 doses, but the second most abundant at high doses. Stronger associations were found between the magnitude of liver injury at 24 hr (quantitated as serum glutamate-pyruvate transaminase activity) and the extent or rate of CCl4 metabolism by pathways leading to CO2 and CHCl3 than by pathways leading to 14C-metabolites bound in liver or excreted in urine. Time-course and pharmacokinetic data indicated that a major pathway of CCl4 metabolism leading to CO2 became impaired within 2 hr after administration of hepatotoxic doses of CCl4.
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PMID:Metabolism of [14C]carbon tetrachloride to exhaled, excreted and bound metabolites. Dose-response, time-course and pharmacokinetics. 643 7

This study reports the results of a biochemical investigation of 80 eating disorder patients and results of an endocrinological investigation of 20 subjects. Of the 80 subjects studied, 22 suffered from anorexia nervosa and 51 were diagnosed as having bulimia. These patient's results were compared to those of 30 control subjects. The eating disorder patients had significantly higher levels of total CO2 calcium, alanine aminotransferase and cholesterol, and significantly lower levels of potassium, chloride and phosphate in the plasma. Hypokalaemia was strongly associated with self-induced vomiting and laxative abuse. Hypercholesterolaemia occurred most commonly in anorexia nervosa patients. Preliminary endocrinological results suggest decreased gonadotrophin levels are associated with binge eating and self-induced vomiting and laxative abuse, as well as with low weight. We feel eating disorder patients should be interviewed and examined by a physician with an interest in this area. Appropriate investigations should be ordered. The physician should also undertake counseling about the short- and long-term sequelae of disordered eating.
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PMID:Hormonal and biochemical abnormalities in women suffering from eating disorders. 644 82

We determined normal reference values from data on sera of 2099 outpatient children (ages one week to 14 years) at our institution. Using a continuous-flow instrument (SMAC, Technicon), we determined the following analytes in each serum sample: glucose, creatinine, uric acid, inorganic phosphorus, sodium, potassium, chloride, total CO2, iron, cholesterol, triglycerides, total protein, albumin, total bilirubin, creatine kinase, lactate dehydrogenase, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and calcium. The resulting data were coded and subsequently processed in an IBM 370 computer, and the reference values (3rd and 97th percentiles) were defined for each analyte. A two-way analysis of variance was also done to determine the influence of age and sex on results of these 20 biochemical tests.
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PMID:Normal reference-intervals for 20 biochemical variables in healthy infants, children, and adolescents. 669 87

Following oral intake or inhalation, halogenated hydrocarbons are metabolized to hepatotoxic intermediates in the liver to only a small extent, the major part being eliminated via the lungs without biochemical transformation. Following intoxication, increased pulmonary elimination of hydrocarbons can be achieved in patients by treatment with CO2-induced hyperventilation. To investigate the efficacy of this new therapy under exact experimental conditions, female Wistar rats received 2.5 ml CCl4/kg BW by gastric intubation and were then treated with CO2-induced hyperventilation. In comparison to untreated animals, hyperventilated rats showed only a few signs of hepatic injury by histological evaluation, whereas massive centrolobular necroses and fatty infiltrations were observed in non-hyperventilated animals. By biochemical assessment, significant decreases of GOT, GPT and GDH activity were observed in the serum, when hyperventilated rats were compared to untreated animals. Moreover, the LD50 for CCl4 was almost trebled after hyperventilation compared to the non-hyperventilated animals. The increased LD50, and the biochemical and histological results therefore substantiate the usefulness of CO2-induced hyperventilation therapy in the treatment of intoxications by hydrocarbons under standardized experimental conditions.
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PMID:Protective effect of CO2-induced hyperventilation on the hepatotoxicity elicited by carbon tetrachloride. 682 Jan 7

The ectomycorrhizal fungus Paxillus involutus efficiently took up exogenously supplied [14C]alanine and rapidly converted it to pyruvate, citrate, succinate, fumarate and to CO2, thus providing direct evidence for the utilisation of alanine as a respiratory substrate. [14C]alanine was further actively metabolised to glutamate, glutamine and aspartate. Exposure to aminooxyacetate completely suppressed 14CO2 evolution and greatly reduced the flow of carbon from [14C]alanine to tricarboxylic acid cycle intermediates and amino acids, suggesting that alanine aminotransferase plays a pivotal role in alanine metabolism in Paxillus involutus.
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PMID:Respiration of [14C]alanine by the ectomycorrhizal fungus Paxillus involutus. 808 30

The retina of honeybee drone is a nervous tissue with a crystal-like structure in which glial cells and photoreceptor neurons constitute two distinct metabolic compartments. The phosphorylation of glucose and its subsequent incorporation into glycogen occur in glia, whereas O2 consumption (QO2) occurs in the photoreceptors. Experimental evidence showed that glia phosphorylate glucose and supply the photoreceptors with metabolic substrates. We aimed to identify these transferred substrates. Using ion-exchange and reversed-phase HPLC and gas chromatography-mass spectrometry, we demonstrated that more than 50% of 14C(U)-glucose entering the glia is transformed to alanine by transamination of pyruvate with glutamate. In the absence of extracellular glucose, glycogen is used to make alanine; thus, its pool size in isolated retinas is maintained stable or even increased. Our model proposes that the formation of alanine occurs in the glia, thereby maintaining the redox potential of this cell and contributing to NH3 homeostasis. Alanine is released into the extracellular space and is then transported into photoreceptors using an Na(+)-dependent transport system. Purified suspensions of photoreceptors have similar alanine aminotransferase activity as glial cells and transform 14C-alanine to glutamate, aspartate, and CO2. Therefore, the alanine entering photoreceptors is transaminated to pyruvate, which in turn enters the Krebs cycle. Proline also supplies the Krebs cycle by making glutamate and, in turn, the intermediate alpha-ketoglutarate. Light stimulation caused a 200% increase of QO2 and a 50% decrease of proline and of glutamate. Also, the production of 14CO2 from 14C-proline was increased. The use of these amino acids would sustain about half of the light-induced delta QO2, the other half being sustained by glycogen via alanine formation. The use of proline meets a necessary anaplerotic function in the Krebs cycle, but implies high NH3 production. The results showed that alanine formation fixes NH3 at a rate exceeding glutamine formation. This is consistent with the rise of a glial pool of alanine upon photostimulation. In conclusion, the results strongly support a nutritive function for glia.
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PMID:Glial cells transform glucose to alanine, which fuels the neurons in the honeybee retina. 812 Jun 29

The uptake, release, and metabolism of alanine were studied in primary cultures of cerebral cortical neurons or astrocytes and cerebellar granule neurons. All three cell types exhibited a saturable, sodium-dependent uptake of alanine with Km values (microM) of 256 +/- 30, 463 +/- 39, and 292 +/- 39, respectively, and Vmax values (nmol/min/mg) of 15.9 +/- 0.7, 7.9 +/- 0.01, and 17.4 +/- 0.8, respectively. The corresponding values (nmol/min/mg) for the specific activity of alanine aminotransferase were 4.7 +/- 0.4, 17.1 +/- 2.5, and 4.5 +/- 0.9 (all values represent the mean +/- SEM). Release of alanine from the cells was rectilinear with time over a 10 hr period in case of astrocytes (40 nmol/hr/mg) and cerebellar granule neurons (21 nmol/hr/mg). In cortical neurons the release rate declined from an initial value of 19 nmol/hr/mg during the first 3 hr to a value of less than 3 nmol/hr/mg during the subsequent 7 hr of incubation. Metabolism of [14C]alanine to 14CO2 was found to have a lag period of 15 min and subsequently the rate of CO2 production was constant over a 45 min period with a value of 0.5 nmol/min/mg in granule neurons and about 0.3 nmol/min/mg in the other two cell types. Altogether the results show that alanine is preferentially produced in and released from astrocytes and accumulated into both GABAergic cortical neurons and glutamatergic cerebellar granule neurons.
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PMID:Uptake, release, and metabolism of alanine in neurons and astrocytes in primary cultures. 837 25

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


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