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)

Growth of a highly-deviated ascites hepatoma (Yoshida AH-130) in rats caused initial hyperplastic enlargement of the liver, followed by progressive reduction to a size lower than that seen in controls. The time-course of this biphasic change in liver weight roughly corresponded to the exponential and stationary phases of tumour growth. Histologically, scattered small foci of perilobular necrosis were observed during the hyperplastic phase and these were consistently associated with a moderate elevation of glutamate-pyruvate transaminase (GPT) activity in the blood plasma. By contrast, signs of necrosis were absent and plasma GTP levels had returned to normal during the phase of hepatic involution, which was characterized by enhanced apoptosis, a type of single-cell death known to be involved in the regulation of tissue size under both normal and pathological conditions. Biochemically, alterations in liver protein mass resulted from changed rates of tissue protein degradation. The apoptotic bodies could either be lost from the liver via blood, lymph and bile, or phagocytosed and degraded by adjacent cells. Disposal of the apoptotic bodies is likely to account, at least in part, for the enhanced rates of liver protein turnover that characterize hepatic involution.
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PMID:Regulation of cell turnover in the livers of tumour-bearing rats: occurrence of apoptosis. 279 40

The concentration of serum immunoreactive prolyl 4-hydroxylase (S-IRPH) was determined in patients with various liver diseases by the radioimmunoassay developed previously. S-IRPH values were elevated in acute hepatitis (p less than 0.01), hepatocellular carcinoma (p less than 0.05), metastatic liver neoplasm (p less than 0.01) and cholestatic diseases (p less than 0.001), but no significant elevation was seen in chronic hepatitis or liver cirrhosis. The mean value of S-IRPH was highest in cholestatic diseases, and next highest in acute hepatitis. In addition to acute hepatitis, S-IRPH was increased in other conditions of hepatocellular damage such as exacerbation of chronic hepatitis or immediately after transcatheter arterial embolization of hepatocellular carcinoma. In cases of hepatocellular damage S-IRPH varied concurrent with cytoplasmic enzyme (AST, ALT and LDH) levels and in cases of cholestatic diseases with biliary enzyme (Al-P and gamma GTP) levels. These properties appear to be unique among serum enzymes. The characteristics of S-IRPH were considered to be related to its unique subcellular localization within the cell, ie the membrane of rough endoplasmic reticulum.
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PMID:Studies on serum immunoreactive prolyl 4-hydroxylase in liver diseases--its elevation both in hepatocellular damage and cholestatic diseases. 284 41

Bass gill microsomal preparations contain a Mg2+-dependent Na+-stimulated ATPase activity in the absence of K+, whose characteristics are compared with those of the (Na+ + K+)-ATPase of the same preparations. The activity at 30 degrees C is 11.3 mumol Pi X mg-1 protein X hr-1 under optimal conditions (5 mM MgATP, 75 mM Na+, 75 mM HEPES, pH 6.0) and exhibits a lower pH optimum than the (Na+ + K+)-ATPase. The Na+ stimulation of ATPase is only 17% inhibited by 10-3M ouabain and completely abolished by 2.5 mM ethacrinic acid which on the contrary cause, respectively, 100% and 34% inhibition of the (Na+ + K+)-ATPase. Both Na+-and (Na+ + K+)-stimulated activities can hydrolyze nucleotides other than ATP in the efficiency order ATP greater than CTP greater than UTP greater than GTP and ATP greater than CTP greater than GPT greater than UTP, respectively. In the presence of 10(-3)M ouabain millimolar concentrations of K+ ion lower the Na+ activation (90% inhibition at 40 mM K+). The Na+-ATPase is less sensitive than (Na+ + K+)-ATPase to the Ca2+ induced inhibition as the former is only 57.5% inhibited by a concentration of 1 X 10(-2)M which completely suppresses the latter. The thermosensitivity follows the order Mg2+--greater than (Na+ + K+)--greater than Na+-ATPase. A similar break of the Arrhenius plot of the three enzymes is found. Only some of these characteristics do coincide with those of a Na+-ATPase described elsewhere. A presumptive physiological role of Na+-ATPase activity in seawater adapted teleost gills is suggested.
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PMID:Ouabain-insensitive Na+ stimulation of a microsomal Mg2+ -ATPase in gills of sea bass (Dicentrarchus labrax L.). 285 46

Leucine and monomethyl succinate initiate insulin release, and glutamine potentiates leucine-induced insulin release. Alanine enhances and malate inhibits leucine plus glutamine-induced insulin release. The insulinotropic effect of leucine is at least in part secondary to its ability to activate glutamate oxidation by glutamate dehydrogenase (Sener, A., Malaisse-Lagae, F., and Malaisse, W. J. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 5460-5464). The effect of these other amino acids or Krebs cycle intermediates on insulin release also correlates with their effects on glutamate dehydrogenase and their ability to regulate inhibition of this enzyme by alpha-ketoglutarate. For example, glutamine enhances insulin release and islet glutamate dehydrogenase activity only in the presence of leucine. This could be because leucine, especially in the presence of alpha-ketoglutarate, increases the Km of glutamate and converts alpha-ketoglutarate from a noncompetitive to a competitive inhibitor of glutamate. Thus, in the presence of leucine, this enzyme is more responsive to high levels of glutamate and less responsive to inhibition by alpha-ketoglutarate. Malate could decrease and alanine could increase insulin release because malate increases the generation of alpha-ketoglutarate in islet mitochondria via the combined malate dehydrogenase-aspartate aminotransferase reaction, and alanine could decrease the level of alpha-ketoglutarate via the alanine transaminase reaction. Monomethyl succinate alone is as stimulatory of insulin release as leucine alone, and glutamine enhances the action of both. Succinyl coenzyme A, leucine, and GTP are all bound in the same region on glutamate dehydrogenase, where GTP is a potent inhibitor and succinyl coenzyme A and leucine are comparable activators. Thus, the insulinotropic properties of monomethyl succinate could result from it increasing the level of succinyl coenzyme A and decreasing the level of GTP via the succinate thiokinase reaction.
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PMID:Regulation of insulin release by factors that also modify glutamate dehydrogenase. 304 28

Postoperative hyperbilirubinemia (Bil greater than or equal to 2, II greater than or equal to 15) was observed in 46.9% of 239 cases of esophageal cancer, since 1969. The incidence increased significantly from 31 to 55.9% after introducing total parenteral nutrition (TPN) for pre-postoperative nutritional support. In retrosternal reconstruction it was significantly higher (57.8%) than any other operative procedures. Further investigation was done in recent 128 cases since 1979. Postoperative hyperbilirubinemia was observed in 59%. The incidence was not different among operative procedures. It was significantly higher in esophagectomy than in total gastrectomy (28%) and in colectomy (12%). Lower nutritional states and longer operative time were predictive factors. Patients with higher bilirubin level (group A: greater than or equal to 3,5) had higher incidence of associated complications than patients with lower bilirubin level (group B: 3.5 greater than greater tha or equal to 2) and patients in control (group C: less than 2). Patients with hyperbilirubinemia alone as a postoperative complication were studied in group A and B. Bilirubin level in both groups reached maximum on 6-7th postoperative days (POD) as gamma GTP and ALP increased rapidly after 3rd-4th POD. The second elevation of GOT and GPT, and incidence of leukocytosis were marked in group A. Thus it was conceived that TPN, malnutrition, effects of extensive operation, postoperative cholestatic change, and infection might contribute to postoperative hyperbilirubinemia.
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PMID:[Clinical analysis of postoperative hyperbilirubinemia following resection of esophageal cancer]. 312 16

4-Hydroxynonenal (HNE), a major aldehyde end-product of lipid peroxidation, induces in vitro a rapid stimulation of rat liver PIP2-phospholipase C. At physiological Ca2+ concentration the effect of the aldehyde is strongly potentiated by guanosine thiotriphosphate (GTP gamma S); GPT gamma S; at higher Ca2+ levels the acceleration of PIP2 breakdown induced by the aldehyde reaches very high values, but is no longer modulated by the presence of GTP gamma S. As the concentration of the aldehyde used (1 micromolar) can be actually reached in tissues, the effects shown in vitro are likely to occur in vivo.
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PMID:Stimulation of phospholipase C activity by 4-hydroxynonenal; influence of GTP and calcium concentration. 325 Sep 44

Three hundred and two intravenous drug addicts (IVDA) from five towns in Northeastern Italy were studied. Of the males, 37/249 (14.8%) were homosexuals and of the females, 29/53 (54.7%) were prostitutes; 118 (39.0%) were alcoholics. AST levels were abnormal in 31.8%, ALT in 45.7%, GTP in 36.4%, and bilirubin in 14.6%. The prevalence of HBsAg (13.9%) and HBeAg (21.4% of HBsAg positive) was significantly higher than in 2,983 controls (4.2% and 6.3%, p less than .001 and p less than .02, respectively). Of the HBsAg positive subjects, 51.7% had anti-HDV antibodies. Among 260 HBsAg negative cases, 146 (56.2%) were anti-HBs and anti-HBc positive, 76 (29.2%) were anti-HBc positive and anti-HBs negative (25 anti-HBe positive and 51 anti-HBe negative), and 38 had no HBV markers. Anti-HIV ELISA positive subjects came to 70.5% (triplicate determination with absolute concordance) and Western blot analysis confirmed the results in 99.1% of ELISA positive and 100% of ELISA negative subjects. The prevalence of anti-HIV was significantly higher in anti-HBc positive than negative cases (p less than .02), even excluding HBsAg positive subjects. Cases negative for HIV and HBV had a significantly lower median duration of drug abuse than those with past or present infection (36 vs 60 months, p less than .001). HIV-related diseases were present in 56.3% of the cases (120/213; PGL in 94, ARC in 24, and AIDS in two).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HIV and HBV infection in intravenous drug addicts from northeastern Italy. 349 7

The interactions of nucleotides with phosphoenolpyruvate carboxykinase were studied by using the stereospecific thiophosphate analogues of GDP and GTP. The metal ion dependent stereoselectivity of these analogues was determined by using steady-state kinetics. The RP and SP isomers of guanosine 5'-O-(1-thiodiphosphate) (GDP alpha S) were substrates with low turnover, and a small preference for the RP isomer was observed. Neither the enzyme-metal nor the nucleotide-metal complex elicited any substantial change in the selectivity. Guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) exhibited no substrate activity for the enzyme, regardless of the cations. This nucleotide was a competitive inhibitor against GDP, however. Both RP and SP diastereomers of guanosine 5'-O-(1-thiotriphosphate) (GTP alpha S) were good substrates for phosphoenolpyruvate carboxykinase; in several cases, depending upon the cation, kcat and/or Vm/Km for the RP isomer is greater than for the substrate GTP. The enzyme-metal complex but not the nucleotide-metal complex affects the relative Km and the Vmax values. In contrast, guanosine 5'-O-(2-thiotriphosphate) (GTP beta S) (SP) is a much better substrate (greater than 50 times) than is GTP beta S (RP). The metal ions have little effect on the selectivity. These results suggest a specific interaction of the beta-phosphate of the nucleotide with the protein. The analogue guanosine 5'-O-(3-thiotriphosphate) (GPT gamma S) serves as a substrate to yield GDP and thiophosphoenolpyruvate. The latter was detected by 31P NMR and was shown to slowly hydrolyze to form phosphoenolpyruvate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Guanosine thiophosphate derivatives as substrate analogues for phosphoenolpyruvate carboxykinase. 391 4

1. Mitochondrial and supernatant aspartate transaminases (EC 2.6.1.1) and supernatant alanine transaminase (EC 2.6.1.2) were purified 89-, 204- and 240-fold respectively, from dolphin muscle. Starch-gel electrophoresis of crude and purified preparations revealed that all three enzymes exist as single forms. 2. K(m) values of alpha-oxoglutarate, alanine, pyruvate and glutamate for the alanine transaminase were 0.45, 8.2, 0.87 and 15mm respectively. For the aspartate transaminases, the K(m) values of alpha-oxoglutarate, aspartate, oxalacetate and glutamate were 0.76, 0.50, 0.10 and 9.4mm respectively, for the mitochondrial form and 0.13, 2.4, 0.06 and 3.2mm respectively, for the supernatant form. 3. In all cases, as the assay pH value was decreased from pH7.3, the K(m) values of the alpha-oxo acids decreased whereas those of the amino acids increased. 4. The apparent equilibrium constants for the aspartate transaminases were independent of pH. These values were 9.2 and 6.8 for the mitochondrial and supernatant forms respectively, where [Formula: see text] 5. Studies of the inhibition of the aspartate transaminases by dicarboxylic acids indicated that these enzymes may be controlled by pools of metabolic intermediates. 6. Three key roles are suggested for the transaminases in the energy metabolism of the diving animal. First, it is believed that a combined action of the transaminases could enhance energy production during hypoxia by providing (a) fumarate from aspartate for the ATP-producing reversal of succinate dehydrogenase, and (b) alpha-oxoglutarate from glutamate for the GTP-producing succinyl thiokinase reaction. Secondly, diving mammals probably accumulate more NADH than other mammals during hypoxia. The aspartate transaminases seem particularly well suited for restoring and maintaining redox balance via the malate-aspartate cycle after aerobic metabolism is resumed. Finally, since the preferred fuel for aerobic work is fat, the combined reactions of the transaminases could be instrumental in providing increased supplies of oxaloacetate for sparking the tricarboxylic acid cycle.
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PMID:Purification and properties of dolphin muscle aspartate and alanine transaminases and thier possible roles in the energy metabolism of diving mammals. 446 40

The translocation of the messenger RNA relative to the ribosome during peptide synthesis represents an example of a mechano-chemical reaction in which the chemical bond energy of GTP is transformed into coordinated motion. Such transformations also occur during the beating of cilia and flagellae, the contraction of muscle and the migration of chromosomes in cell division. In protein synthesis the functional geometric and energetic conditions for this transformation are well defined. For each peptide bond formed, the ribosome moves one codon along the mRNA (towards the 3' end) and one molecule of GTP is hydrolysed. Although the basic requirements of this reaction have been elucidated, the mechanism is still unresolved. We demonstrate here that translocation can be analysed as a series of binding equilibria shifted by one irreversible, GTP-consuming step. The shift in the binding equilibrium is induced by the transfer of the peptidyl moiety to the (A) site-bound aminoacyl (AA)-tRNA. This results in the A site-bound tRNA having an increased affinity for the high-affinity (P) site, and a strengthened association with the mRNA. Elongation factor (EF) G . GPT catalyses removal of the deacylated tRNA, empties the P site and at the same time loosens ribosome-mRNA association. The result of these changes is that peptidyl(PP)-tRNA . mRNA is shifted from the A site to the P site, binding of AA-tRNA . EF-Tu . GPT to the vacant A site ensuring that the process is irreversible.
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PMID:Steps of mRNA translocation in protein biosynthesis. 702 51


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