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)

The only exogenous substrates oxidized by mitochondria isolated from the flight muscle of the Japanese beetle (Popillia japonica) are proline, pyruvate and glycerol 3-phosphate. The highest rate of oxygen consumption is obtained with proline. The oxidation of proline leads to the production of more NH3 than alanine, indicating a functioning glutamate dehydrogenase (EC 1.4.1.2). Studies of mitochondrial extracts confirm the presence of a very active glutamate dehydrogenase, and this enzyme is found to be activated by ADP and inhibited by ATP. These extracts also show high alanine aminotransferase activity (EC 2.6.1.2) and a uniquely active "malic' enzyme (EC 1.1.1.39). The "malic' enzyme is activated by succinate and inhibited by ATP and by pyruvate. It is suggested that the input of tricarboxylate-cycle intermediate from proline oxidation is balanced by the formation of pyruvate from malate, and the complete oxidation of the majority of the pyruvate. Studies of the steady-state concentrations of mitochondrial CoASH and CoA thioesters during proline oxidation show a high succinyl (3-carboxypropionyl)-CoA content which falls on activating respiration with ADP. There is a concomitant rise in CoASH. However, the reverse transition, from state-3 to state-4 respiration, causes only very slight changes in acylation. The reasons for this are discussed. Studies of the mitochondrial content of glutamate, 2-oxoglutarate, malate, pyruvate, citrate and isocitrate during the same phases of proline oxidation give results consistent with control at the level of glutamate dehydrogenase and isocitrate dehydrogenase during proline oxidation, with the possibility of further control at "malic' enzyme. During the oxidation of pyruvate all of the tricarboxylate-cycle intermediates and NAD(P)H follow the pattern of changes described in the blowfly (Johnson & Hansford, 1975; Hansford, 1974) and isocitrate dehydrogenase is identified as the primary site of control.?2OAuthor
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PMID:The nature and control of the tricarboxylate cycle in beetle flight muscle. 120 Sep 85

We report a 41-year-old male of citrullinemia associated with argininosuccinate acid synthetase deficiency. He was admitted to the Hitachi General Hospital because of finger tremor, restlessness and urinary incontinence. He had short stature and a poor appetite. Laboratory evaluation was summarized as follows: mild hypoglycemia, low plasma cortisol levels, delayed response of 17-OHCS and 17-KS to ACTH administration in urine, and delayed response of plasma ACTH level to insulin administration. In this case, ACTH deficiency is estimated to be a dysfunction of the hypothalamus. Replacement therapy of hydrocortisone improved his symptoms. He was readmitted to the hospital because of delirium and confusion, two weeks after the hydrocortisone administration. At that time, he had flapping tremor. Laboratory examination revealed hyperammonemia (NH3: 231 micrograms/dl) and mild elevation of GOT and GPT. Serum and urinary amino acid determination showed marked elevation of citrulline (478.1 nmol/ml in serum, 4681.2 mumol/day in urine). Lactulose administration, low protein diet and plasmapheresis were started, but he went into a coma. Without any improvement, he died on the 29th hospital day. Autopsy examination of the liver disclosed fatty change. Adrenal cortex depicted severe atrophy. Biochemical analysis of urea cycle enzymes of the liver and kidney showed decreased activity of argininosuccinate synthetase (liver: 0.0022 U/mg protein, 5% of that normal liver, kidney: 0.003 IU/mg protein, 20% of that in normal kidney). Citrullinemia associated with ACTH deficiency have not reported in the literature. It may be presumed that ACTH deficiency is concerned with the delayed onset of hyperammonemia. The relation between citrullinemia and endocrinological abnormalities is also discussed.
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PMID:[A case of citrullinemia associated with isolated ACTH deficiency, rapidly developing coma]. 133 25

We have previously reported that Drosophila Kc cells require glutamine for maximal expression of heat shock proteins in stressed conditions (Sanders and Kon: J. Cell. Physiol. 146:180-190, 1991). The mechanism of this effect has been investigated by comparing the metabolic utilization of glutamine in conditions which support hsp expression with that of glutamate in conditions where up to 100-fold less hsp is synthesized. This comparison showed that free ammonia was generated by cells incubated in the presence of glutamine in 37 degrees C (heat shock) conditions, but not at 25 degrees C, and not in the presence of glutamate in either normal or heat shock conditions. There was no difference in the amount of [14C]O2 generated from either [14C]-labeled amino acid in the tricarboxylic acid cycle, but three- to four-fold more alanine was synthesized in cells incubated in glutamine than in glutamate. Treating the cells with aminotransferase inhibitors to artificially increase NH3 release raised hsp expression in the presence of glutamate to maximal levels characteristic of glutamine. This potentiation correlated with inhibition of alanine aminotransferase. Since only NH3 production correlated with hsp expression in heat shock conditions in the presence of glutamine, and NH3 addition to glutamate also resulted in maximal hsp expression, we measured glutamine production in glutamate plus NH3 and observed net glutamine synthesis. The supposition that glutamine itself is responsible for the regulatory changes supporting maximal hsp expression was supported by the finding that the glutamine analog, 6-diazo-5-oxo-L-norleucine (DON), mimicked the effects of glutamine. We conclude that glutamine imposes regulatory changes which alter nitrogen metabolism and support hsp expression in Kc cells.
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PMID:Glutamine and glutamate metabolism in normal and heat shock conditions in Drosophila Kc cells: conditions supporting glutamine synthesis maximize heat shock polypeptide expression. 134 46

A 2-month-old boy was admitted to our hospital because of poor sucking and jaundice. There were no abnormalities during the whole period of pregnancy and at birth. His mother was a HBeAb positive HBsAg carrier, but prophylactic maneuver such as anti-HB immunoglobulin and HB vaccine was not performed on him at birth. Physical examination on admission revealed mild disturbance of consciousness. The laboratory findings showed marked increments of serum bilirubin, GOT, GPT, and NH3, and prolongation of prothrombin time, activated partial thromboplastin time and hepaplastin test. Thus, he was diagnosed as fulminant hepatitis and treated with exchange transfusion once or twice a day. Biochemical data improved gradually, but hypocoagulable states remained unchanged. At that time we decided to use Factor VII concentrate, because we found that, among several coagulation factors, factor VII activity decreased most rapidly after exchange transfusion. The alternate therapy of exchange transfusion and Factor VII concentrate improved his coagulation abnormality without any side effects. Our experience suggests that the combination therapy of exchange transfusion and Factor VII concentrate may be useful for management of fulminant hepatitis, particularly for uncontrollable coagulopathy.
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PMID:[Successful treatment of an infant with fulminant hepatitis by factor VII concentrate]. 260 16

In experiments on 6 sheep the authors found the following enzyme activities in bacteria in the rumen fluid, bacteria adhering to the epithelium of the rumen wall and bacteria adhering to food particles in the rumen (given in nkat X g-1 bacterial dry weight): GDH (NADH): 725 +/- 165, 558 +/- 127, 661 +/- 153; GDH (NADPH): 558 +/- 338, 255 +/- 88, 565 +/- 139; GOAT (NADH): 46 +/- 23, 67 +/- 31, 66 +/- 14; GOGAT/NADPH: 58 +/- 27, 56 +/- 15, 65 +/- 29; GS: 153 +/- 65, 69 +/- 35, 71 +/- 32; ALT: 71 +/- 25, 43 +/- 20, 52 +/- 11; AST: 52 +/- 12, 33 +/- 16, 28 +/- 15. The results show that, except for GDH (NADPH), there were no significant differences between the given enzyme activities in the rumen fluid and in bacteria adhering to the rumen wall and to food. Adherent rumen bacteria have the same potential possibilities as the rumen fluid bacteria for the utilization of ammonia, particularly for the synthesis of glutamic acid, glutamine, alanine and aspartic acid, with the above enzymes as catalysts. By means of the GS/GOGAT system, adherent rumen bacteria can probably synthesize glutamic acid in the presence of a limited NH3 concentration in the rumen.
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PMID:Ammonia-utilizing enzymes of adherent bacteria in the sheep's rumen. 286 70

The aim of this paper is to elucidate the cause of death after 90 min of normothermic partial (2/3) ischemia of the liver and to examine the effects of glucagon, somatostatin, insulin, prednisolone and oral administration of polymyxin B (PB). The animals 24 hr after partial ischemia for 90 min were divided into two groups; namely, animals with normal appearance and those with moribund state. There were no significant differences in the plasma level of S-GOT, S-GPT, amino acids, NH3 or insulin, or in morphometrically estimated volume ratio of necrotic hepatocytes between the two groups of rats. The blood glucose level, however, was significantly decreased (31 +/- 28 mg/100 ml, n = 6) in the moribund rats with a higher incidence of positive Limulus gelation tests as compared with the rats with normal appearance (149 +/- 19, n = 5). The 1-day and 1-week survival rates of the animals were 42/62 (69%) and 32/61 (53%), respectively. A glucagon injection (1.5 mg/kg, after ischemia) was effective to elevate the 1-day survival rate (14/14), but failed to increase the 1-week survival rate (11/14). On the other hand, a somatostatin injection (100 micrograms/kg, after ischemia) or PB treatment (15 mg/kg/day x 5-9, before ischemia) succeeded to increase the 1-week survival rate (20/22 p less than 0.01 and 17/17 p less than 0.01, respectively), although no significant amelioration in transaminase levels or volume ratio of necrosis was demonstrated. It could be seen that a moribund state after partial ischemia was accompanied by severe hypoglycemic shock, and that the injection of somatostatin after ischemia or the annihilation of gram-negative bacteria by means of oral administration of polymyxin B before ischemia prevented the occurrence of the hypoglycemic shock.
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PMID:Postischemic liver damage in rats: effect of some therapeutic interventions on survival rate. 629 17

The activity of certain key enzymes involved in glutamic acid metabolism was studied in purified brain mitochondria and in mitochondrial subfractions separated in a discontinuous 1.2--1.6 mol/l sucrose gradient. Alanine aminotransferase and glutamate dehydrogenase were found to be matrix enzymes and aspartate aminotransferase to be associated with the inner mitochondrial membranes. After the purified mitochondria had been separated into 5 subfractions, aspartate aminotransferase and NAD+-dependent isocitrate dehydrogenase were found to be bound to the lighter mitochondrial subfractions settling at the 1.4--1.5 mol/l sucrose boundary while alanine aminotransferase, 4-aminobutyrate transaminase and glutamate dehydrogenase were associated with the heavier subfractions settling below 2.4 mol/l sucrose. The highest specific activity of the given enzymes was found in the subfraction settling at the 1.4--1.5 mol/l sucrose boundary, the only exception being alanine aminotransferase activity, whose maximum was found in the subfractions settling in 1.5 and 1.6 mol/l sucrose. It was concluded that alanine aminotransferase, in conjunction with glutamate dehydrogenase, is linked to NH3 binding and to the oxidation of reduced adenine nucleotides; in addition, alanine aminotransferase is presumed to have the function of transporting glutamate from the mitochondria to the extramitochondrial space.
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PMID:Alanine aminotransferase and some other enzymes in different populations of free brain cortex mitochondria. 645 52

The retina of honeybee drone is a nervous tissue with a crystal-like structure in which glial cells and photoreceptor neurons constitute two distinct metabolic compartments. The phosphorylation of glucose and its subsequent incorporation into glycogen occur in glia, whereas O2 consumption (QO2) occurs in the photoreceptors. Experimental evidence showed that glia phosphorylate glucose and supply the photoreceptors with metabolic substrates. We aimed to identify these transferred substrates. Using ion-exchange and reversed-phase HPLC and gas chromatography-mass spectrometry, we demonstrated that more than 50% of 14C(U)-glucose entering the glia is transformed to alanine by transamination of pyruvate with glutamate. In the absence of extracellular glucose, glycogen is used to make alanine; thus, its pool size in isolated retinas is maintained stable or even increased. Our model proposes that the formation of alanine occurs in the glia, thereby maintaining the redox potential of this cell and contributing to NH3 homeostasis. Alanine is released into the extracellular space and is then transported into photoreceptors using an Na(+)-dependent transport system. Purified suspensions of photoreceptors have similar alanine aminotransferase activity as glial cells and transform 14C-alanine to glutamate, aspartate, and CO2. Therefore, the alanine entering photoreceptors is transaminated to pyruvate, which in turn enters the Krebs cycle. Proline also supplies the Krebs cycle by making glutamate and, in turn, the intermediate alpha-ketoglutarate. Light stimulation caused a 200% increase of QO2 and a 50% decrease of proline and of glutamate. Also, the production of 14CO2 from 14C-proline was increased. The use of these amino acids would sustain about half of the light-induced delta QO2, the other half being sustained by glycogen via alanine formation. The use of proline meets a necessary anaplerotic function in the Krebs cycle, but implies high NH3 production. The results showed that alanine formation fixes NH3 at a rate exceeding glutamine formation. This is consistent with the rise of a glial pool of alanine upon photostimulation. In conclusion, the results strongly support a nutritive function for glia.
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PMID:Glial cells transform glucose to alanine, which fuels the neurons in the honeybee retina. 812 Jun 29

An inverse relation is known to link blood potassium with renal synthesis and the release of ammonia. Given the liability of hyperammonemia for precipitating hepatic encephalopathy (HE), 28 patients affected by stage I HE were equally divided into two groups and maintained up to their death at the highest (5.4-5.5 mEq/l) or the lowest (3.5-3.6 mEq/l) normokalemia levels. When compared with the lowest normokalemia group, the highest one showed an early, albeit transient, improvement in the mental state (as assessed by both EEG and psychiatric investigations) and to a lesser extent in hepatic functions (as assessed by the variations in serum bilirubin, GPT, GGT and plasma prothrombin time). In the highest normokalemia group the survival was also prolonged. The cause of this improvement may be related to the induced decrease in blood pH, the consequent depression of renal ammoniagenesis and the rise in the arterial and urine NH+4/NH3 ratios. These factors reduce the entry of ammonia into the cells and enhance the urinary excretion of this metabolite, respectively.
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PMID:The importance of the highest normokalemia in the treatment of early hepatic encephalopathy. 816 17

Our bioartificial liver (BAL) consists of porcine hepatocytes attached to beads and plasma perfused through the system. The function of our BAL lasts for approximately 7 hours. The objective of the present study was to investigate the efficacy of Nafamostat Mesilate (NM), a protease inhibitor and potent complement inhibitor, for improving the performance of the BAL. The experimental groups were divided as follows; the NM group (n=7) where the BAL had porcine hepatocytes with 3.8x10(-4) M, of NM, and the control group where the BAL had no NM. Plasma obtained from patients suffering from hepatic failure was perfused through the BAL for 10 hours. The viability of the porcine hepatocytes and the levels of alanine aminotransferase (ALT) in the human plasma were measured during perfusion. After the 10-hour perfusion, another human hepatic failure plasma was perfused for an additional 1 hour and then the function of the BAL was evaluated. After the 10-hour perfusion, the viability of the hepatocytes in the NM group was 51 +/- 7%, whereas that in the control group was rapidly reduced by 35 +/- 5%. Although the levels of ALT in the human plasma in both groups increased with the perfusion time, those in the NM group were significantly lower than those in the control group (p < 0.05). These results suggest that NM prevented damage to the porcine hepatocytes in human hepatic failure plasma as compared to the control group. In the human hepatic failure plasma before perfusion, the partial thrombin time (PT) and the plasma ammonia (NH3) levels were 19.8 +/- 12% and 288 +/- 102 microg/dl, respectively. Fischer's ratios were 0.98 +/- 0.39. Even after the 10-hour perfusion, the BAL in the NM group significantly improved the levels of PT (38 +/- 10%; p < 0.05), NH3 (214 +/- 34 microg/dl; p < 0.05) and Fischer's ratios (1.4 +/- 0.3; p < 0.05). On the other hand, the BAL in the control group did not show any improvement in those parameters. In conclusion, NM was found to help in maintaining the viability of porcine hepatocytes in human hepatic failure plasma, thereby allowing the porcine hepatocyte-based BAL to function much better.
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PMID:Efficacy of Nafamostat Mesilate for improving the performance of a bioartificial liver using porcine hepatocytes. 1049 59


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