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)

Laparoscopic surgery causes a reduction in hepatic blood flow due to a number of factors, including raised intra-abdominal pressure, the neurohumoral response to surgical stress and the effect of patient position. The clinical significance of the phenomenon is not fully understood. Plasma concentrations of alcohol dehydrogenase (AD) and glutathione S-transferase (GST), which are concentrated in the centrilobular acinus of the liver, sensitively reflect hepatic hypoperfusion, and can be used to monitor reductions in hepatic blood flow. We compared perioperative AD, GST, aspartate aminotransferase (AST, normal range 14-32 IU litre(-1)) and alanine aminotransferase (ALT, normal range 8-41 U litre(-1)) concentrations in patients undergoing laparoscopic cholecystectomy or laparoscopic colectomy to study how patient position and surgical manipulation of the liver affect hepatocellular integrity during laparoscopy. There were significant postoperative increases in AD and GST in the cholecystectomy group [mean (SD) peak concentration 10.8 (4.7) U litre(-1) and 113 (55) microg litre(-1) respectively]. Although the duration of pneumoperitoneum was longer in the colectomy group, there were no comparable perioperative increases in AD and GST in this group [peak concentration 4.0 (4.0) U litre(-1) and 33 (35) microg litre(-1) respectively]. AST and ALT on the first postoperative day were significantly higher in the laparoscopic cholecystectomy group (41 and 34 U litre(-1) respectively) than in the laparoscopic colectomy group (24 and 18 U litre(-1); P<0.05 for each). These results indicate that patient position and the effects of surgical manipulation of the liver affect perioperative hepatic perfusion significantly.
 ...
PMID:Subclinical hepatic dysfunction in laparoscopic cholecystectomy and laparoscopic colectomy. 1187 31

Acetolactate synthase (ALS; EC 4.1.3.18) inhibition is the primary mechanism of action of imazethapyr (IM). However, the precise mechanisms that links ALS inhibition with plant death have not been elucidated. Supply of IM to pea (Pisum sativum L) plants produced an immediate cessation of growth, caused a 50% inhibition of the in vivo ALS activity within 1 day of treatment, and a remarkable accumulation (2.7-times) of free amino acids after 3 days. Carbohydrates (soluble and starch) were accumulated in both leaves and roots. Accumulation of soluble sugars in roots preceded that of starch in leaves, suggesting that the accumulation of carbohydrates in leaves is not the reason for the arrested root growth. A transient pyruvate accumulation was observed in roots, 1 day after the onset of IM supply. This was coincident with an increase in pyruvate decarboxylase (EC 4.1.1.1), and later increases in alcohol dehydrogenase (EC 1.1.1.1), lactate dehydrogenase (EC 1.1.1.27), and alanine amino transferase (EC 2.6.1.2) activities. This enhancement of fermentative activities was coincident with a slight decrease in aerobic respiration. The overall data suggest that the impairment of ALS activity may lead to a fermentative metabolism that may be involved in growth inhibition and plant death.
 ...
PMID:Imazethapyr, an inhibitor of the branched-chain amino acid biosynthesis, induces aerobic fermentation in pea plants. 1197 25

The effect of treatment with Saeng-Maek-San (SMS) Complex (SMS1 or SMS2) upon rat hepatocytes exposed to alcohol was investigated. We compared the serum biochemistry and liver histology of rats administered both alcohol and SMS to control rats treated with alcohol alone. SMS treatment resulted in a significant reduction in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and triglycerides (TG) compared to the control rats. In contrast, expression levels of alcohol dehydrogenase (ADH) were increased. Electron microscopy indicated that administration of SMS preserved the structure of organelles, including the nucleus and mitochondria. In addition, lipid droplets and secondary lysosomes were observed in the control rats. These data suggest that SMS represents an excellent candidate for protection of rat hepatocytes from alcohol-mediated damage.
 ...
PMID:Saeng-Maek-San, a medicinal herb complex, protects liver cell damage induced by alcohol. 1241 58

The link between alcohol consumption and liver disease is not direct and several factors including autoimmunity to hepatocyte components have been implicated. We have previously identified alcohol dehydrogenase (ADH) as an autoantigen in autoimmune liver disease and in a proportion of patients with alcoholic liver disease. The aim of the present study is to investigate the association between the presence of anti-ADH antibodies, alcohol consumption and severity of liver damage in alcoholic patients. The presence of antibodies to human ADH beta2 and horse ADH was investigated in 108 patients with documented history of alcohol consumption and alcohol related liver disease, 86 being active alcohol abusers and 22 on sustained alcohol withdrawal, 39 with non-alcohol related disease and 22 normal subjects. Antibodies to either ADH form were more frequently detected in active alcohol abusers (55/86, 64%) than in patients on sustained alcohol withdrawal longer than 6 months (1/8, 13 %, P < 0.005), HBV infection (2/8, 25 %, P=0.03), non-alcohol related disease (9/29, 23 %, P < 0.0001) and in normal controls (3/22, 14 %, P < 0.0001); were more frequent in patients with cirrhosis than in those with steatosis (26/34, 76 % vs 34/64, 53 %, P=0.02); and were associated with elevated levels of ALT (anti-ADH beta2, P < 0.05), immunoglobulin A (P < 0.05) and gamma-glutamyl transpeptidase (P=0.01). Anti-ADH antibody positive serum samples were able to inhibit the enzymatic activity of ADH. These findings suggest that anti-ADH antibodies may be triggered by alcohol consumption and act as a disease activity marker in alcoholic liver disease.
 ...
PMID:Alcohol dehydrogenase: an autoantibody target in patients with alcoholic liver disease. 1569 22

The inhibition of branched-chain amino acid (BCAA) biosynthesis was evaluated in pea plants in relation to the ability for induction of fermentative metabolism under aerobic conditions. Chlorsulfuron and imazethapyr (inhibitors of acetolactate synthase, ALS, EC 4.1.3.18) produced a strong induction of pyruvate decarboxylase (PDC, EC 4.1.1.1) and alcohol dehydrogenase (ADH, EC 1.1.1.1) activities and a lesser induction of lactate dehydrogenase (LDH, EC 1.1.1.27) and alanine aminotransferase (AlaAT, EC 2.6.1.2) activities in roots. Inhibition of the second enzyme of the BCAA biosynthesis (ketol-acid reductoisomerase, KARI, EC 1.1.1.86) by Hoe 704 (2-dimethylphosphinoyl-2-hydroxyacetic acid) and CPCA (1,1-cyclopropanedicarboxylic acid) enhanced fermentative enzyme activities including PDC, ADH, and AlaAT. Fermentative metabolism induction occurring with ALS- and KARI-inhibitors was related to a higher expression of PDC. In the case of KARI inhibition, it is proposed that fermentation induction is due to an inhibition of ALS activity resulted from an increase in acetolactate concentration. Fermentative metabolism induction in roots, or at least ethanolic fermentation, appeared to be a general physiological response to the BCAA biosynthesis inhibition.
 ...
PMID:Fermentative metabolism is induced by inhibiting different enzymes of the branched-chain amino acid biosynthesis pathway in pea plants. 1615 77

The blood alcohol level cycle (BALC) of the intragastric tube feeding model first described by Tsukamoto et al., has three separate essential mechanistic components. The first is the requirement for an intact functioning thyroid. The evidence for this is that propylthiouracil or severance of the pituitary stalk completely prevents the cycle. What happens instead of the cycle is that the blood alcohol level rises to a lethal level when ethanol is given continuously at a dose of 11 g/kg/day by stomach tube. When excess thyroid hormone is given orally it markedly attenuates the cycle because it interferes with the changes in the level of thyroid hormone during the cycle. The second component is norepinephrine. Catecholamines are markedly elevated at the peaks of the cycle. Both propranolol and phenoxybenzamine, which are beta- and alpha-blockers, prevent the cycle. Also, when catecholamines are fed in excess in the form of ephedrine, the cycle is eliminated. The third element essential to the cycle is the generation of NAD to support the oxidation of alcohol by alcohol dehydrogenase. When complex I (NADH dehydrogenase) of the mitochondrial electron transport chain is inhibited by feeding rotenone, the cycle is totally eliminated and blood alcohol levels remain constant at 200 mg/%. Thus NADH increases and NAD decreases at the peak of the cycle. Without the fluxuation of NAD, ADH activity cannot fluctuate during the cycle and the cycle is prevented. The significance of the BALC in the understanding of alcohol liver disease pathogenesis is that there's a marked difference in the gene expression and liver toxicity when the peaks and troughs of the cycle are compared. The expression of 1000+ genes is either two-fold up or down regulated as determined by microarray analysis. At the peaks there is increased liver pathology, especially inflammatory changes in the liver associated with an increase of iNOS expression. The genes responsive to hypoxia inducible factor 1alpha (HIF1alpha) regulation are increased including the expression of erythropoietin, adrenomedullin and adrenergic receptor alpha 1a and d. The expression of prolyl hydroxylase, which destabilizes HIF1alpha, increases when the BAL drops to low levels during the cycle. The level of oxygen, as measured on the surface of the liver, is decreased at the peaks, compared to control livers. The NADH/NAD ratio is markedly increased and ATP levels are markedly decreased at the BAL peaks. Also, endotoxin in the blood is very high at the peaks and very low at the troughs. When the blood alcohol levels fall during the cycle, there is an increase in ALT, suggesting that reoxygenation from the hypoxic state at the peaks causes an ischemic reperfusion injury-like lesion in the liver. At this time there is also an increase in expression of many important enzymes such as manganese SOD. Genes such as c-fos and CTGF are increased in expression. These contrasting findings at the peaks and troughs indicate that the blood alcohol levels, which fluctuate up and down, change the gene expression and the pathology of the liver.
 ...
PMID:The pathogenesis and significance of the urinary alcohol cycle in rats fed ethanol intragastrically. 1634 1

The protective effect of a 30 kDa glycoprotein (GF-AS) isolated from the stem bark of Acanthopanax senticosus against acute and chronic alcohol-induced hepatotoxicity were studied. N-terminal amino acid sequence of GF-AS showed NH(2)-Val-Ala-Tyr-Pro-Trp-Ala-Gly-Phe-Ala-Leu-Ser-Leu-Glx-Pro-Pro-Ala-Gly-Tyr-. GF-AS significantly increases the activities of alcohol-metabolizing enzymes, including alcohol dehydrogenase, microsomal ethanol metabolizing system, and acetaldehyde dehydrogenase in rats acutely treated with alcohol, resulting in decreased plasma alcohol levels. GF-AS also increases the activities of antioxidant enzymes and glutathione level. Markers of liver injury induced by alcohol: elevated serum levels of aspartate aminotransferase, alanine aminotransferase, triglyceride and cholesterol, are reduced by GF-AS in both acutely and chronically treated rats. The activities of lipogenic enzymes including malic enzyme, glucose-6-phosphate dehydrogenase, and 6-phosphoglucuronic acid dehydrogenase in chronic alcohol-treated rats are significantly decreased by GF-AS. Furthemore, GF-AS improves histological change in fatty liver and hepatic lesions induced by alcohol. Collectively, GF-AS may alleviate alcohol-induced hepatotoxicity through increasing ethanol and lipid metabolism, as well as antioxidant defense systems in livers injured by acute- and chronic-alcohol treatment.
 ...
PMID:Glycoprotein isolated from Acanthopanax senticosus protects against hepatotoxicity induced by acute and chronic alcohol treatment. 1646 37

Alanine aminotransferase, otherwise called glutamate-pyruvate aminotransferase (GPT), activity increases up to fourfold during several days of anaerobic induction in barley (Hordeum vulgare L.) roots, reaching a maximum activity of 13 international units per gram fresh weight. This increase in activity paralleled the increase in alcohol dehydrogenase activity in the same root tissue. Upon return to aerobic conditions, the induced GPT activity declined with an apparent half-life of 2 days. The isozyme profile of GPT in barley root tissue comprised one band of activity; in maize there were three bands of activity, the bands with greater mobility had much lower activity. Native polyacrylamide gel electrophoresis indicated that the induction of GPT activity results from an increase in the level of activity of these bands; no other activities were detected. When root tissue was induced under different levels of hypoxia (0%, 2%, 5%, and 21% O(2)), changes in GPT activity were found to increase with lower levels of oxygen. Comparisons of GPT induction in barley, maize (Zea mays), rye, (Secale cereale) and wheat (Triticum aestivum) indicate that this enzyme is induced in the root tissue of all of these cereals; however, anaerobic root conditions do not result in the induction of GPT activity in leaf tissue. The dependence of GPT induction on high levels of nitrate in the media was tested by comparing activity levels in Hoagland solution and a nitrate-free nutrient solution. GPT activity was induced to similar levels under both conditions. These results indicate that alanine aminotransferase shows a very similar pattern of induction to alcohol dehydrogenase in barley root tissue and may be important in anaerobic glycolysis.
 ...
PMID:Anaerobic induction of alanine aminotransferase in barley root tissue. 1666 27

Variants in alcohol dehydrogenase (ADH) genes differ between ethnic groups and have, in some studies, been found to be associated with alcohol dependence and alcoholic liver disease. This study sought to determine whether an association exists between ADH (ADH1C previously ADH3, ADH1B*2 previously ADH2*2) genotypes, alcohol dependence, drinking history, and liver function tests in the two major ethnic groups of Trinidad and Tobago (TT). One hundred and forty-five alcohol-dependent individuals of both East Indian (Indo-TT) and African (Afro-TT) ancestry, and 108 controls matched by age, sex, and education participated in the study. Serum levels of alanine and aspartate aminotransferase (ALT, AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma-glutamyltransferase (GGT) as well as presence of HIV, hepatitis B surface antigen, and anti-hepatitis C virus antibody were determined. There was a significant difference in the distribution of ADH1C allele polymorphisms between the ethnic groups (P<.0001). Forty-three percent of the Indo-TT were found to have one ADH1C*2 allele and 5% were homozygous, whereas, only 23% of Afro-TT had one allele and one was homozygous. Only three individuals had an ADH1B*2 allele (one Indo-TT alcohol dependent, two Indo-TT controls). The ADH1C*2 allele was significantly associated with alcohol dependence overall and within Indo-TT ancestry, however, it was not associated with current or heaviest alcohol consumption levels. Individuals with at least one ADH1C*2 allele also had significantly elevated levels of ALP (P<.02) and GGT (P<.02) as compared to individuals homozygous for ADH1C*. Additionally, GGT levels were also found to be elevated (P<.02) within Indo-TT alcohol dependents with at least one ADH1C*2 allele but not within the Afro-TT alcohol dependents with that allele. A linear regression that included alcohol dependence and levels of alcohol consumption confirmed that levels of serum GGT were significantly associated with the ADH1C*2 genotype. These results suggest that ADH1C polymorphisms are associated with alcohol dependence and alcohol associated elevations of liver enzymes in a population with a low frequency of ADH1B2 alleles.
 ...
PMID:ADH1C*2 allele is associated with alcohol dependence and elevated liver enzymes in Trinidad and Tobago. 1713 60

The present study investigates the hepatoprotective effect of fenugreek seed polyphenolic extract (FPEt) against ethanol-induced hepatic injury and apoptosis in rats. Chronic ethanol administration (6 g/kg/day x 60 days) caused liver damage that was manifested by the elevation of markers of liver dysfunction--aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin and gamma-glutamyl transferase (GGT) in plasma and reduction in liver glycogen. The effects on alcohol metabolizing enzymes such as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were studied and found to be altered in the alcohol-treated group. Ethanol administration resulted in adaptive induction of the activities of cytochrome p450 (cyt-p-450) and cytochrome-b5 (cyt-b5) and reduction in cytochrome-c-reductase (cyt-c-red) and glutathione-S-tranferase (GST), a phase II enzyme. Further, ethanol reduced the viability of isolated hepatocytes (ex vivo) as assessed by the trypan blue exclusion test and increased hepatocyte apoptosis as assessed by propidium iodide staining (PI). Treatment with FPEt restored the levels of markers of liver injury and mitigated the alterations in alcohol metabolizing and detoxification enzymes and the electron transport component cytochrome-c reductase. Increased hepatocyte viability and reduced apoptotic nuclei were observed in FPEt-treated rats. These findings demonstrate that FPEt acts as a protective agent against ethanol-induced abnormalities in the liver. The effects of FPEt are comparable with those of a known hepatoprotective agent, silymarin.
 ...
PMID:Fenugreek (Trigonella foenum graecum) seed polyphenols protect liver from alcohol toxicity: a role on hepatic detoxification system and apoptosis. 1748 88


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>