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)

A pattern of results is reported which was found to be common among patients who had intrahepatic cholestasis (IHC) which was rarely found in patients with other hepatic conditions. The pattern was recognized from over 1000 cases suspected of hepatobiliary disease. 29 were diagnosed with IHC, and excluding 4, 25 revealed the following etiological pattern: chlorpromazine (12 patients); pregnancy and oral contraceptive use (8); and other (5). As opposed to patients with acute and chronic hepatic disease, IHC sufferers had relatively normal values for immunoglobulins and antibody titers. A disproportionate elevation of serum bilirubin vis-a-vis serum enzymatic activities separated potential IHC cases into intra- and extrahepatic cholestasis. The following factorial evaluations were useful in distinguishing hepatic disease states: 1) when the sum of the activities of serum alkaline phosphatase, 5'-nucleotidase, aspartate and alanine amiotransferases, and isocitrate dehydrogenase was divided by the serum bilirubin concentration, there was good resolution of the distinction between patients with IHC and those with primary biliary cirrhosis, early and late viral hepatitis, cholelithiasis, and pancreatic and bile duct cancers. 2) Resolution was also achieved when the numerator included alkaline phosphatase, 5'-nucleotidase, and aspartate aminotransferase, but not when alkaline phosphatase alone, or alkaline phosphatase combined with 5'-nucleotidase, was used. The essential lesion in IHC is an excretory defect.
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PMID:Biochemical features of intrahepatic cholestasis. 45 73

The presence and particle association of various hydrolytic enzymes in Naegleria fowleri has been studied in whole cell extracts of trophozoites in an effort to establish authentic markers for surface membrane and lysosomal components. Evidence from the experiments reported here indicates that in N. fowleri a) acid proteinase, N-acetylglucosaminidase, and acid phosphatase are associated with cytoplasmic granules closely resembling lysosomes; b) 5'-nucleotidase is associated with the surface membrane, probably on the external surface; c) aspartate aminotransferase is associated with mitochondria; d) alpha-D-glucosidase and an aminopeptidase have bimodal distributions, activity being associated with both the surface membrane and lysosomal particles.
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PMID:Subcellular distribution of hydrolases in Naegleria fowleri. 299 80

Twelve serum analytes [triglycerides, cholesterol, total and conjugated bilirubin, high-density-lipoprotein cholesterol (HDL-C), alkaline phosphatase (AP), gammaglutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), beta-glucuronidase (beta-glu), alanine aminopeptidase (AAP), and 5'-nucleotidase (5'nuc)] were measured to investigate their correlation with exposure to polychlorinated biphenyls (PCBs) and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT). The relationship between serum lipids, lipophilic toxicants, and the analytes was also evaluated. The beta-glu, 5'nuc, triglycerides, cholesterol, and total bilirubin correlated positively and significantly with log concentrations of serum total PCBs and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), a metabolite of DDT. The more highly chlorinated PCBs (Aroclor 1260) had significant, positive correlations with several serum analytes, but the less chlorinated PCBs (Aroclor 1242) correlated significantly and negatively only with HDL-cholesterol. Triglyceride- and cholesterol-rich lipoproteins were added to serum to determine the effects of lipids on these assays. Several were spuriously elevated. AP and beta-glu were not affected by lipoprotein addition with the methods used in this study. AAP was increased significantly only at triglyceride concentrations exceeding 400 mg/dl. Lipoproteins may be elevated because of deranged lipid metabolism in response to PCBs, or PCBs may be elevated because elevated lipoproteins are present, as in familial triglyceridemia, a relatively common dyslipoproteinemia. Because this relationship is not well understood with respect to cause and effect, we propose the further use in epidemiological investigations of assay methods that are little affected by blood lipids yet are correlated with PCB concentrations. Congener-specific quantification of PCBs would help elucidate the effects of PCBs on assays used to monitor health effects.
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PMID:Effects of polychlorinated biphenyls and lipemia on serum analytes. 302 64

Hepatic function can be monitored using exogenous (e.g., sulfobromophthalein, indocyanine green, antipyrine, aminopyrine, galactose) and endogenous substances (e.g., bile acids, PT/PTT, albumin, ammonia, bilirubin). Test of hepatic necrosis include aspartate aminotransferase, and alanine aminotransferase. The hepatobiliary system can be assessed using alkaline phosphatase, 5'-nucleotidase, gamma-glutamyl transpeptidase, ultrasound, and iminodiacetic acid scans.
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PMID:Monitoring hepatic function. 306 53

High-performance liquid chromatography analysis of acid-extracted tissues revealed decreases of high-energy nucleotides and increases in low-energy nucleotides and metabolites in heart, diaphragm, and liver but not in kidneys of diabetic rats. In comparison with nondiabetic rats, the total adenine nucleotide content of diabetic rat heart and diaphragm but not liver decreased, indicating an increase in catabolism of AMP. Maximal initial rates of the AMP catabolic enzymes 5'-nucleotidase, adenosine deaminase, and AMP deaminase were elevated in the hearts of BB/Wistar and streptozocin-induced diabetic rats. Nucleotide salvage enzymes adenylosuccinate synthetase and adenylosuccinate lyase were elevated above normal in the diabetic heart, whereas hypoxanthine-guanine phosphoribosyl transferase was not altered. Cytosolic-to-mitochondrial ratios from maximal initial rates after correction for mitochondrial breakage were increased above controls in diabetic hearts for nucleoside diphosphokinase and aspartate aminotransferase. Nucleotide levels, degradation rates, and substrate compartmentation between cytosol and mitochondria are discussed in relation to concurrent diabetes.
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PMID:Adenine nucleotide metabolism in hearts of diabetic rats. Comparison to diaphragm, liver, and kidney. 336 Feb 19

The activities of adenosine deaminase, purine nucleoside phosphorylase, membrane 5'-nucleotidase and DNA content in thymus and spleen lymphocytes as well as the immune function of T and B lymphocytes of the spleen of C3HA mice with o-AAT-induced hepatomas were studied 1, 3 weeks and 3, 8, 12 months after o-AAT treatment was instituted. In the early stages of the hepatocarcinogenesis (up to 3 months), the elevation of the activity of all the enzymes and DNA content in thymocytes and T and B lymphocytes was observed. These changes coincided with the enhancement of the immune responses that manifested in the increased content of PFC, EA-RFC and high response to PHA and Con A. In the late stages, the decreased activities of purine nucleosides and nucleotide metabolizing enzymes correlated with disturbances of lymphocyte differentiation and lowering of the host immune response.
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PMID:[Changes in purine metabolism and in the immune response in the thymic and splenic lymphocytes of C3HA mice during chemical hepatocarcinogenesis]. 633 63

The effect of carrot extract on carbon tetrachloride (CCl4)-induced acute liver damage was evaluated. The increased serum enzyme levels (viz., glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, lactate dehydrogenase, alkaline phosphatase, sorbitol and glutamate dehydrogenase) by CCl4-induction were significantly lowered due to pretreatment with the extract. The extract also decreased the elevated serum bilirubin and urea content due to CCl4 administration. Increased activities of hepatic 5'-nucleotidase, acid phosphatase, acid ribonuclease and decreased levels of succinic dehydrogenase, glucose-6-phosphatase and cytochrome P-450 produced by CCl4 were reversed by the extract in a dose-responsive way. Results of this study revealed that carrot could afford a significant protective action in the alleviation of CCl4-induced hepatocellular injury.
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PMID:Hepatoprotective activity of carrot (Daucus carota L.) against carbon tetrachloride intoxication in mouse liver. 750 Jun 38

PD 138142-15 is a substituted urea hypolipidemic and potential anti-atherosclerotic agent. To determine the toxicity of PD 138142-15, beagle dogs were given oral doses of 1, 10, 30, and 100 mg/kg daily for 13 weeks. Two animals at 100 mg/kg were euthanized during Week 5 due to poor condition. Clinical findings included decreased serum albumin at > or = 30 mg/kg, and increased ALP (up to 30-fold) and 5'-nucleotidase activities (up to 9-fold) at doses > or = 10 mg/kg. ALT and AST activities were elevated only at 100 mg/kg. There was a two- to threefold increase in cytochrome P450 content of hepatic microsomes from all treated animals and increases in liver weights at 10 mg/kg and above. Hepatic changes included hepatocellular hypertrophy and increased cytoplasmic eosinophilia at > or = 10 mg/kg; single cell necrosis of hepatocytes was noted in moribund animals. ACTH-stimulated cortisol levels were decreased at 30 and 100 mg/kg. Adrenal cholesterol esters were decreased at 10 mg/kg and above, while total adrenal cholesterol was decreased at > or = 30 mg/kg. These changes correlated with adrenal cortical zonal atrophy, principally of the zona fasciculata and zona reticularis, present at 30 and 100 mg/kg. Plasma concentrations of PD 131842-15 increased with increasing dose; plasma levels were significantly lower during Week 12 than those on Day 1, possibly due to autoinduction. Overt hepatotoxicity occurred at 100 mg/kg, whereas hepatic changes at 10 and 30 mg/kg were consistent with cytochrome P450 induction. The hepatic lesions were reversible within 4 weeks, while adrenal lesions were still evident after 4 weeks without treatment.
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PMID:Hepatic and adrenal toxicity of a novel lipid regulator in beagle dogs. 758 16

A total of 25 apparently healthy adults (13 men and 12 women), 29.5 years (SD = 3.6 years) of age, served as subjects in a 24-h study conducted in Barcelona, Spain, in the spring of 1990. The group had a homogeneous pattern of meals, activity, and behavior. Six blood samples were collected at 4-h intervals over a single 24-h period beginning at 10:00 h. The oral temperature was measured at 2-h intervals to facilitate an independent biological time reference for the local population being studied. The serum concentration of 12 enzymes of clinical interest were measured in each sample: creatine kinase, creatine kinase 2, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, cholinesterase, lactate dehydrogenase, lactate dehydrogenase 1, 5'-nucleotidase, pancreatic alpha-amylase, and triacylglycerol lipase. We supposed that all experimental data obtained for a quantity came from a single "hypothetical subject" that represented the central tendency of the population and then these data were analyzed for circadian rhythm by single cosinor. A statistically significant circadian rhythm was detected in all quantities studied (p < or = 0.05) except for serum concentrations of pancreatic alpha-amylase and triacylglycerol lipase. The maximum daily rhythmic variation was approximately 10% (interval, 6-14%) for all quantities studied except pancreatic alpha-amylase (2.6%). This rhythmic variation is greater than the analytical variation except for 5'-nucleotidase and pancreatic alpha-amylase. The acrophases for the quantities studied (except that of triacylglycerol lipase) coincide with times near those of the oral temperature acrophase (18:01 local time). The results of this study will doubtless contribute to further documentation of the structure of the human circadian timing system and to establishment of time-qualified reference intervals for a defined group of subjects.
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PMID:Circadian rhythms of serum concentrations of 12 enzymes of clinical interest. 810 Apr 88

Human recombinant tumor necrosis factor was administered to rats in small doses to determine whether it causes changes in the activity of liver enzymes similar to those observed in cancer growing extrahepatically. Intraperitoneal injection of increasing doses of tumor necrosis factor (20-100 micrograms/kg/day for 5 days) resulted in a 20-50% decrease in hepatic alanine aminotransferase (P < or = 0.05), a 10-20% decrease in aspartate aminotransferase (P < or = 0.04), and a 50-200% increase in alkaline phosphatase (P < or = 0.02). The activity of hepatic 5'-nucleotidase was unchanged. In the serum, there was no significant change in the activity of any of the enzymes. Histologically, there was no damage detectable by light or electron microscopic examination of the liver, and no evidence of biliary obstruction. However, in frozen liver sections stained histochemically for alkaline phosphatase, there was a dramatic increase in the activity of this enzyme in hepatocytes, which was confined to the bile canaliculi. There was also a 3- to 9-fold increase in the mitotic activity of hepatocytes. Comparable changes have been reported in the tumor-free liver of animals with cancer.
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PMID:Tumor necrosis factor induces enzymatic changes in liver comparable to those in extrahepatic cancer. 850 61


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