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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Background/Aim: Hepatic venography with a positive-contrast medium has been reported as a method for evaluating liver disease. However, the contrast medium used in this method provides insufficient portal vein observation and may cause severe liver injuries. Carbon dioxide (CO(2)), a negative-contrast medium, may be able to depict the portal vein system with minimal hepatic toxicity. The aim of this study was to evaluate the usefulness and side-effects of balloon-occluded hepatic venography with CO(2) (CO(2) venography) and to evaluate the correlation between retrograde portogram and liver function in patients with cirrhosis. Subjects and methods: The subjects consisted of 23 biopsy-proven cirrhotic patients (male:female, 16:7; age, 58+/-12 years, range 34-80). The causes of cirrhosis were alcohol intake in ten, HCV infection in ten, HBV infection in one, primary biliary cirrhosis in one and Budd-Chiari syndrome in one. Of these patients, six were complicated with hepatocellular carcinoma (HCC). CO(2) venography was performed with an occlusion balloon catheter, and 25 ml of CO(2) was infused. CO(2) portograms were scored as follows: 0, no visualization of portal veins; 1, visualization of peripheral portal branches; 2, unilateral first portal branch; 3, bilateral first portal branches; 4, main portal vein; 5, left gastric vein, superior mesenteric vein and splenic vein. Hepatic venous pressure gradient (HVPG), cardiac functions, biochemical analysis, blood gas analysis and oxygen (O(2)) saturation monitoring were measured simultaneously. Arterio-portography was also performed. To evaluate the usefulness of CO(2) venography in patients with HCC accompanied by portal vein tumor thrombus (PVTT), three patients were also examined. Results: No significant changes in ALT, AST, O(2) saturation or blood gas data were observed after CO(2) venography. A statistically significant positive correlation was observed between CO(2) portogram scores and Child-Pugh scores (r=0.68, P=0.003). The correlations between CO(2) portogram scores and HVPG, and the forms of gastroesophageal varices in patients without PVTT and major shunts were not significant. The CO(2) portogram score was significantly higher in patients with alcoholic liver cirrhosis than in those with HCV-positive cirrhosis (P=0.04). Cavernous transformation and peripheral portal branches were demonstrated in patients with HCC accompanied by PVTT. These findings could not be observed by arterio-portography. Conclusion: CO(2) venography to obtain retrograde portogram is a safe and useful method for evaluating the portal vein system and liver function in patients with liver cirrhosis.
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PMID:Evaluation of balloon-occluded hepatic venography with carbon dioxide for portography and correlation between retrograde portogram and liver function in patients with liver cirrhosis. 1105 28

The aim of the study was to evaluate myocardial perfusion in acute carbon monoxide poisoned patients using rest and stress Tc 99m-MIBI SPECT scintigraphy. There were 29 study patients (15 men and 14 women) aged from 14 to 46 years poisoned acutely with CO at home. Measurement of COHb, blood lactate level, duration of exposure and ECG examination were performed on admission to the Clinic. The enzymes activity (ALT, AST, CBK) were evaluated after 24 hours. The first rest Tc99m-MIBI SPECT was performed in all patients two to five days after intoxication. Fifteen of the patients underwent the control examination: stress and rest scintigraphy six months after CO exposure. Moving track exercise according to the Bruce protocol was used in each the patients. The control rest scintigraphy was performed 48 hours after exercise. Abnormal, differently intensified scans were noted in all the subjects: 5 patients had a I degree of pathological changes, 7 patients had II degree, 16--III degree and 1 patient had a IV degree of pathological changes. In 14 of the patients with pathological scintigraphic scans the normal EKG curves were noted. The mean COHb level was 35.0 +/- 7.22%, the blood lactate concentration was 4.4 +/- 3.7 mmol/L. The average duration of exposure was 108.4 +/- 163.9 min. Effort related ischemia was not noted in 10 of the patients who underwent control examination. An improvement in rest scintigraphic scans was stated in 12, and no changes were observed in 3 of the controlled patients. Deterioration was not found in any patient. No correlation between ECG results and scintigraphic image of myocardium was found. Tc 99m-MIBI SPECT scintigraphy is a more sensitive method than electrocardiography and measurement of enzymes activity for the evaluation of CO cardiotoxicity in acute poisoning. The method enables evaluation of the localization and disease extent.
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PMID:Usefulness of rest and forced perfusion scintigraphy (SPECT) to evaluate cardiotoxicity in acute carbon monoxide poisoning. 1145 Mar 57

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

Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme into biliverdin, carbon monoxide, and iron. HO-1, an inducible form, is thought to contribute to resistance to various types of oxidative stress. Doxorubicin (DOX) produces clinically useful responses in a variety of human cancers. We reported previously that prior administration of DOX ameliorated subsequent hepatic ischemia and reperfusion injury. The aim of this study was to examine whether this pharmacological preconditioning was useful for another type of hepatic injury induced by a non-surgical method. When a high dose of DOX (10 mg/kg body weight) was administered directly to rat liver via the portal vein, serum aspartate transaminase (AST) and alanine transaminase (ALT) levels increased markedly 24 hr after the injection. Under this condition, zinc-protoporphyrin IX, a specific inhibitor of HO-1, caused both serum AST and ALT levels to be elevated further. When a low dose of DOX (5 mg/kg body weight) was administered to rats via the tail vein as pharmacological preconditioning 3 days before the injection of a high dose of DOX via the portal vein, the levels of serum AST and ALT in rats clearly were improved as compared with rats without the preconditioning. Expression of HO-1 in the liver was confirmed 3 days after the administration of a low dose of DOX. In addition, prior administration of zinc-protoporphyrin IX abolished the effect of DOX preconditioning. Immunohistochemical analysis showed that the positive staining of HO-1 protein induced by a low dose of DOX was localized to histiocytes infiltrating periportal areas. These results strongly suggest that pharmacological preconditioning with DOX may generally help to attenuate subsequent oxidant-induced hepatic injury.
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PMID:Pharmacological preconditioning with doxorubicin. Implications of heme oxygenase-1 induction in doxorubicin-induced hepatic injury in rats. 1170 58

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

The results of myocardial (99mTc-MIBI SPECT) perfusion scintigraphy according to clinical evaluation, ECG, biochemical factors of necrosis and indicators of carbon monoxide (CO) poisoning severity are described in the paper. Under examination there were 88 young (mean age 26 +/- 8.5) acutely CO poisoned patients without previous cardiac illness history, treated at the Department of Clinical Toxicology Jagiellonian University Medical College in Krakow in 1996 to 2002. Measurement of COHb level, blood lactate concentration, duration of exposure and ECG examination were performed on admission. The enzymes activity ALT, AST, CK, MB-CK, was evaluated after 24-48 h. The severity of CO poisoning was estimated basing on age, duration of exposure, COHb level, blood lactate concentration and the patient neurological state on admission. 99mTc-MIBI SPECT was performed on days 1 to 5 post admission. The abnormalities in scintigraphic scans were assessed according to arbitrary accepted scale (0-IV). Conventional biomarkers creatine kinase, ALT and AST were insufficient for evaluation the heart injury in CO cutely poisoned patients. A statistically significant differences in the blood lactate concentration with regard to degree of scintigraphic changes have been observed. The ECG curves monitored from admission to discharge were analyzed in the study. Tachycardia was observed in all the patients but no statistically significant differences were found between the subgroups divided according to the degree of scintigraphic scans. Conductivity disturbances were detected mainly in patients qualified to higher then the first degree of scintigraphic changes. ECG signs of myocardial ischemia were the most frequent in patients with biggest pathological changes in 99mTc-MIBI scans. The changes in 99mTc-MIBI SPECT were observed in the majority of acutely CO poisoned patients. The mutual dependence of patient's condition based on neurological symptoms, carbon monoxide poisoning severity scoring and the degree of scintigraphy changes was found. The examination performed indicate that 99mTc-MIBI SPECT scintigraphy can be method of choice for evaluation the heart injury in patients after acute CO intoxication.
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PMID:Clinical and scintigraphic (99mTc-MIBI SPECT) heart evaluation in young acutely carbon monoxide poisoned patients. 1456 89

Substantial fluid shifts occur during liposuction as wetting solution is infiltrated subcutaneously and fat is evacuated, causing potential electrolyte imbalances. In the porcine model for large-volume liposuction, plasma aspartate aminotransferase and alanine transaminase levels were elevated following liposuction. These results raised concerns for possible mechanical injury and/or lidocaine-induced hepatocellular toxicity in a clinical setting. The first objective of this human model study was to explore the effect of the liposuction procedure on electrolyte balance. The second objective was to determine whether elevated plasma aminotransferase levels were observed subsequent to large-volume liposuction. Five female volunteers underwent three-stage, ultrasound-assisted liposuction. Blood samples were collected perioperatively. Plasma levels of sodium, potassium, venous carbon dioxide, blood urea nitrogen, chloride, and creatinine were determined. Liver function analyte levels were measured, including albumin, total protein, aspartate aminotransferase, and alanine transaminase, alkaline phosphatase, gamma-glutamyl transpeptidase, and total bilirubin. To further define intracellular enzyme release, creatine kinase levels were measured. Mild hyponatremia was evident postoperatively (134 to 136 mmol/liter) in four patients. Hypokalemia was evident intraoperatively in all subjects (mean +/- SEM; 3.3 +/- 0.16 mmol/liter; range, 3.0 to 3.4 mmol/liter). Hypoalbuminemia and hypoproteinemia were observed throughout the study (baseline: 2.9 +/- 0.2 g/dl; range, 2.6 to 3.5 g/dl), decreasing to 10 to 40 percent 24 hours postoperatively (2.0 +/- 0.2 g/dl; range, 1.7 to 2.1 g/dl). Aspartate aminotransferase, alanine transaminase, and creatine kinase levels were significantly elevated after the procedure (190 +/- 47.1 U/liter, 50 +/- 7.7 U/liter, and 11,219 +/- 2556.7 U/liter, respectively) (p < 0.01). Release of antidiuretic hormone and even mildly hypotonic intravenous fluid infiltration have long been known to cause hyponatremia postoperatively. Intraoperative hypokalemia is associated with hypocarbia and respiratory alkalosis and the elevated epinephrine levels observed in the concurrent study. Factors having the greatest initial impact on diminished serum albumin and protein levels postoperatively are redistribution and hemodilution. Subsequent diminished viscosity may significantly affect postoperative hemodynamics. Elevated aspartate aminotransferase, alanine transaminase, and creatine kinase levels are associated with skeletal muscle injury, adipocyte lysis, and/or hepatic damage. Therefore, tissue injury is associated with large-volume liposuction as observed in several cellularly released enzymes. Future clinical studies are required to determine the degree of injury and specific tissues that are damaged or sensitive to mechanical trauma and/or drugs used in large-volume liposuction.
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PMID:Electrolyte and plasma enzyme analyses during large-volume liposuction. 1531 60


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