Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diversion of portal blood in congenital portosystemic shunts (CPSS) results in liver atrophy and passage of toxins into the systemic circulation causing hepatic encephalopathy. In some dogs, there is indirect evidence for hepatic insufficiency, but histologic findings are equivocal. This study determined whether hepatocyte integrity in PSS is comprised at a subcellular level using analytical subcellular fractionation of liver biopsies. Six dogs with CPSS had hypoproteinemia (6/6), increased serum alkaline phosphatase (6/6) and alanine aminotransferase (4/6) activity, hypocholesterolemia (6/6), and decreased blood urea (2/6). Liver biopsy specimens had increased activities (mU/mg protein) of alkaline phosphatase (17.9 +/- 10.1; controls 5.1 +/- 5.3: P less than 0.01), but not of other plasma membrane enzymes. There were increased activities of endoplasmic reticular (neutral alpha-glucosidase: 1.67 +/- 0.7; controls 0.86 +/- 0.2: P less than 0.01) and lysosomal enzymes (N-acetyl-beta-glucosaminidase: 12.6 +/- 2.3; controls 6.24 +/- 2.7: P less than 0.01; alpha-mannosidase: 0.85 +/- 0.5; controls 0.39 +/- 0.3: P less than 0.05). Subcellular fractionation on reorientating sucrose density gradients showed a high-density peak of alkaline phosphatase suggestive of a specific increase in the biliary canalicular component of enzyme activity. Neutral alpha-glucosidase was shifted to denser fractions, indicative of an increase in the proportion of rough-to-smooth endoplasmic reticulum and consistent with enhanced synthesis of membranous enzymes. There was also evidence for increased fragility of intracellular organelles, particularly lysosomes. In contrast, histology showed either no abnormalities or minor degenerative changes compatible with hepatic underperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic organelle pathology in dogs with congenital portosystemic shunts. 161 98

Bloodstream forms of Trypanosoma brucei have been screened for the presence of enzymes that could serve as markers for the plasma membrane, flagellar pocket, lysosomes, endoplasmic reticulum and Golgi apparatus in order to study the subcellular organization of the digestive system of the parasite. Acetylesterase, acid DNase, acid phosphatase, acid phosphodiesterase, acid proteinase, acid RNase, alanine aminotransferase, galactosyl transferase, alpha-glucosidase, inosine diphosphatase and alpha-mannosidase were partially characterized and their assays optimized for pH-dependent activity, linearity of reaction with respect to incubation time and enzyme concentration, and the effect of inhibitors and activators. The association of these enzymes with particulate material and the presence of structural latency were investigated. Acid proteinase and alpha-mannosidase are particle-bound and latent in cytoplasmic extracts; they can be activated and solubilized in part by Triton X-100. Similar results were obtained for acid phosphatase, acid phosphodiesterase and inosine diphosphatase. Neutral alpha-glucosidase, though partly sedimentable, does not show latency and is readily solubilized by the detergent. Galactosyl transferase is firmly membrane-bound even in the presence of 0.1% Triton X-100. Cell fractionation by differential centrifugation and density equilibration on sucrose gradients revealed that both alpha-mannosidase and acid proteinase are associated with organelles that band at a density of about 1.20 g/cm3. Inosine diphosphatase, galactosyl transferase, acid phosphatase and acid phosphodiesterase sediment predominantly as microsomal constituents equilibrating at densities between 1.13 and 1.15 g/cm3. In addition, inosine diphosphatase and galactosyl transferase exhibit considerable activity at higher densities (1.18-1.25 g/cm3). Neutral alpha-glucosidase is mainly recovered in the nuclear and microsomal fraction; its particulate part equilibrates as a single band at rho = 1.22 g/cm3. Acetylesterase and acid DNase are largely soluble, whereas acid RNase does not produce distinct sedimentation and banding profiles. In intact cells, neutral alpha-glucosidase and acid phosphatase appear to be highly accessible to their substrates. It is tentatively concluded that (a) acid proteinase and alpha-mannosidase are lysosomal enzymes, (b) acid phosphatase and acid phosphodiesterase are associated with the flagellar pocket and part of the former enzyme probably with the endoplasmic reticulum, (c) galactosyl transferase is a constituent of the Golgi apparatus, and (d) alpha-glucosidase may serve as a marker for the plasma membrane. Inosine diphosphatase may also be derived from the latter structure.
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PMID:Subcellular fractionation of Trypanosoma brucei bloodstream forms with special reference to hydrolases. 624 76

Dogs are particularly susceptible to development of glucocorticoid-induced hepatopathy, but the mechanisms are not well understood. We investigated the pathogenesis of glucocorticoid hepatopathy by examining sequential morphologic and biochemical changes in the liver of dogs during steroid administration. Six adult Beagles were given prednisolone acetate (4mg/kg of body weight, once daily for 24 days IM). Serum samples and percutaneous liver biopsy specimens were obtained before the start of the study (treatment day [TD] 0) and at TD 5, 10, 15, and 25. There were significant (P < 0.05) and progressive increases in serum activities of alkaline phosphatase, gamma-glutamyltransferase, and alanine transaminase. Light microscopic changes in liver biopsy specimens included progressive hepatocellular swelling and vacuolation. Electron microscopy revealed glycogen accumulation, peripheral displacement of organelles, and prominent dilatation of bile canaliculi, compared with findings at TD 0. Liver biopsy specimens taken at TD 25 had significantly (P < 0.05) increased activities of the plasma membrane enzymes, alkaline phosphatase and gamma-glutamyltransferase, and 5'-nucleotidase was significantly (P < 0.001) decreased. Subcellular fractionation on reorientating sucrose density gradients revealed high-density peaks of alkaline phosphatase and gamma-glutamyltransferase, compatible with a specific increase in the biliary canalicular component of the enzyme activities. Neutral alpha-glucosidase activity was shifted to the denser fractions, indicative of an increase in the proportion of rough to smooth endoplasmic reticulum and consistent with enhanced synthesis of plasma membrane proteins. There also was evidence for progressive increase in fragility of intracellular organelles, particularly lysosomes. These findings indicate that glucocorticoid hepatopathy in dogs is associated with progressive alterations not only to the plasma membrane, but also to other subcellular organelles.
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PMID:Subcellular pathologic features of glucocorticoid-induced hepatopathy in dogs. 757 58

A water-soluble Touchi-extract (TE) exerts a potent inhibitory activity against rat intestinal alpha-glucosidase in foodstuffs, and elicited anti-glycemic effects in rats and humans with single-bolus oral administration. In the present study, genetically modified diabetic model KKAy mice were used to examine the long-term effects of TE. Eight-week-old male KKAy mice were fed with CE-2 chow containing 0.08 and 0.4% of TE for 60 days. In the latter group, fasting blood glucose levels decreased (6.68 +/- 0.41 mmol/L) significantly (p<0.05) after a 60-day ingestion period compared with controls (8.75 +/- 0.54 mmol/L). Moreover, postprandial blood glucose levels were also significantly reduced (16.79 +/- 2.28 mmol/L; p<0.01) after ingesting TE for only 30 days compared with controls (28.49 +/- 0.59 mmol/L). On oral TE treatment for 60 days, postprandial increases in the blood glucose level after oral loading of sucrose (2 g/kg) at 30 (p<0.05) and 60 (p<0.01) min were significantly depressed compared with controls. Indexes for serum lipids; viz., total cholesterol (p<0.05) and triglyceride (p<0.01) levels significantly decreased after TE ingestion. Indexes for hepatic functions, such as glutamic-oxaloacetic transaminase (p<0.01), glutamic-pyruvic transaminase and gama-glutamyl transpeptide levels, were similarly suppressed. Organ weights of the heart, kidney, jejunum, liver and spleen increased in control KKAy mice due to hyperinsulinemia. Interestingly, the respective organ weights decreased (p<0.05, 0.01) and the jejunum length was reduced (p<0.05) significantly in the TE-treated groups. All in all, TE demonstrated an anti-hyperglycemic effect and may have potential use in the management of non-insulin-dependent diabetic mellitus.
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PMID:Fermented soybean-derived Touchi-extract with anti-diabetic effect via alpha-glucosidase inhibitory action in a long-term administration study with KKAy mice. 1178 46

Pioglitazone, a new thiazolidinedione agent,has been shown to increase insulin sensitivity in clinical trials. Pioglitazone HCI was rapidly absorbed within one hour, achieved peak concentrations at 2-3 h, and was eliminated from serum at 24-36 h. Pioglitazone demonstrated dose-dependent pharmacokinetics. Food did not significantly affect the pharmacokinetic profile of pioglitazone. The pharmacokinetic profile of sulfonylurea agents was not significantly altered by concurrent administration with pioglitazone. Pharmacokinetic studies in healthy volunteers and in patients with type 2 diabetes indicated that pioglitazone may be administered once daily. In patients with type 2 diabetes, pioglitazone as monotherapy and in combination with sulfonylureas or an alpha-glucosidase inhibitor significantly reduced fasting blood glucose, HbA1c, triglycerides, and free fatty acids, and significantly increased HDL-cholesterol. Pioglitazone demonstrated either minor increases or decreases in cholesterol with no adverse effect on LDL-cholesterol. No patients experienced jaundice or ALT elevations > or = three times the upper limit of normal. Adverse events were mild and transient; all subjects returned to their baseline health status or laboratory tests upon withdrawal from, or completion of, the studies. Based upon these preliminary studies, full-scale clinical investigations were conducted in Japan, the United States, and Europe. As a result, in many countries pioglitazone has gained approval for use in patients with type 2 diabetes.
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PMID:Pioglitazone: a review of Japanese clinical studies. 1190 Mar 11

In vitro study revealed that pancreatic lipase inhibitory activity of C. asiatica extract was significantly higher than rutin but lower than orlistat, an anti-obesity drug. alpha-Amylase inhibitory activities of C. asiatica extract and rutin were significantly lower than acarbose, an anti-diabetic drug. Inhibition of alpha-glucosidase activity by C. asiatica extract, rutin, and acarbose was not different. The in vivo study substantiated the in vitro results. C. asiatica extract (1000 and 2000 mg/4 mL/kg), rutin (1000 mg/4 mL/kg), and orlistat (45 mg/4 mL/kg) significantly decreased plasma glucose, triglyceride and total cholesterol levels in lipid emulsion-induced hyperlipidemic rats at 3 h. However, plasma aspartate aminotransferase and alanine aminotransferase levels did not show significant change. The present work further supports that the C. asiatica extract and its bioactive rutin may help managing hypolipidemic and hypoglycemic effects.
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PMID:Hypolipidemic and hypoglycemic effects of Centella asiatica (L.) extract in vitro and in vivo. 2534 45