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:3.1.3.9 (glucose-6-phosphatase)
3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adult (male, 75-90 days old) and immature rats (both sexes, 11-12 days old) were treated with allyl alcohol or bromobenzene to induce periportal or centrilobular hepatic injury, respectively. Histologically confirmed liver lesions were produced in adult rats with both treatments. In adult rats, allyl alcohol decreased hepatic cytochrome P-450, benzphetamine N-demethylation, and ethoxyresorufin O-deethylation activities all by about 30%, whereas bromobenzene influenced these parameters differently: cytochrome P-450 was lowered by 55%, benzphetamine N-demethylation by 80%, and ethoxyresorufin O-deethylation by 90%. Cytochrome c reductase, 5'-nucleotidase, glucose-6-phosphatase, and glutamate-pyruvate transaminase activities were not significantly influenced. In immature rats, allyl alcohol did not produce histopathological alterations in liver, but did lower both cytochrome P-450 concentration (30%) and ethoxyresorufin O-deethylation (75%). Benzphetamine N-demethylation was not significantly affected. Bromobenzene produced typical centrilobular liver damage and a decrease of both cytochrome P-450 (20%) and ethoxyresorufin O-deethylation (50%). Benzphetamine N-demethylation was increased slightly, but not significantly. The differences in effects of the two hepatotoxins in adult vs immature rats seem to indicate that the hepatocellular heterogeneity of xenobiotic metabolism which is seen in adult liver (perivenous vs periportal areas) is not well developed in the immature animal.
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PMID:Functional hepatocellular heterogeneity determined by the hepatotoxins allyl alcohol and bromobenzene in immature and adult Fischer 344 rats. 300 82

Hepatocytes were isolated from immature and adult rat liver by retrograde perfusion with calcium free buffer, followed by enzymic digestion, and separated into subpopulations by centrifugal elutriation. Several subpopulations with increasing cell diameters were distinguished. The smaller cells were attributed to the periportal area, the larger ones to the perivenous (centrilobular) region. Profiles of total cytochrome P-450 concentration, benzphetamine N-demethylation and ethoxyresorufin O-deethylation, NADPH-cytochrome c-reductase, glucose-6-phosphatase and glutamate-pyruvate-transaminase activities were determined in all subpopulations. With adult hepatocytes an increasing cytochrome P-450 concentration with increasing cell diameter (increasing from periportal to perivenous hepatocytes) could be observed, paralleled by increasing activities of benzphetamine N-demethylation and ethoxyresorufin O-deethylation activities. While NADPH-cytochrome c-reductase did not show a distinct zonation, glucose-6-phosphatase and glutamate-pyruvate-transaminase revealed increasing activities with increasing cell diameter. Immature hepatocytes (rats aged 11-15 days) were smaller, and more fragile. They could not be isolated with the same enzyme solution as adult hepatocytes and they did not show any zonation of cytochrome P-450 concentration, although the zonation of benzphetamine N-demethylation and ethoxyresorufin O-deethylation was almost fully developed. For NADPH-cytochrome c-reductase a zonation with higher activities in the perivenous cells could be demonstrated, in contrast to the lack of zonation in adult rats. Glucose-6-phosphatase activity showed a decline with increasing cell diameter in immature hepatocytes, whereas glutamate-pyruvate-transaminase activity did not show any zonation. In rats aged 20 days the zonation of these parameters in liver was in between that of younger and older animals. Zonation of the liver lobule develops postnatally with individual patterns for the different parameters.
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PMID:Separation and characterization of hepatocytes from immature and adult rats into distinct subpopulations by centrifugal elutriation. 322 57

Fetal and maternal sheep were studied to determine whether changes in gluconeogenic enzyme activities could be detected in the liver and/or kidney associated with maternal nutritional deprivation. Thirteen ewes and 16 fetuses were sacrificed in the fed state, while 13 ewes with 17 fetuses were sacrificed after 5 days of fasting, all at 125 days gestation (term = 147 days). Fetal weight was decreased in the fasted versus fed group (2.86 +/- 0.56 versus 3.61 +/- 0.58 kg, p less than 0.001). Tissues were analyzed for glucose-6-phosphatase, fructose-1,6-diphosphatase, pyruvate carboxylase, phosphoenolpyruvate carboxykinase, glutamate oxaloacetate aminotransferase, and glutamate pyruvate aminotransferase. In maternal liver, four of the six enzymes increased significantly during fasting, whereas none of the enzymes increased in maternal kidney. In fetal hepatic tissue, five of the six enzymes (with the exception of pyruvate carboxylase) increased during maternal fasting and three of the enzymes increased in renal tissue. These data are consistent with the potential for increased rates of gluconeogenesis in the ovine fetus during periods of compromised maternal nutrition.
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PMID:Effects of fasting on gluconeogenic enzymes in the ovine fetus. 372 67

In incubated colonocytes isolated from rat colons, the rates of utilization O2, glucose or glutamine were linear with respect to time for over 30 min, and the concentrations of adenine nucleotides plus the ATP/ADP or ATP/AMP concentration ratios remained approximately constant for 30 min. Glutamine, n-butyrate or ketone bodies were the only substrates that caused increases in O2 consumption by isolated incubated colonocytes. The maximum activity of hexokinase in colonic mucosa is similar to that of 6-phosphofructokinase. Starvation of the donor animal decreased the activities of hexokinase and 6-phosphofructokinase, whereas it increased those of glucose-6-phosphatase and fructose-bisphosphatase. Isolated incubated colonocytes utilized glucose at about 6.8 mumol/min per g dry wt., with lactate accounting for 83% of glucose removed. These rates were not affected by the addition of glutamine, acetoacetate or n-butyrate, and starvation of the donor animal. Isolated incubated colonocytes utilized glutamine at about 5.5 mumol/min per g dry wt., which is about 21% of the maximum activity of glutaminase. The major end-products of glutamine metabolism were glutamate, aspartate, alanine and ammonia. Starvation of the donor animal decreased the rate of glutamine utilization by colonocytes, which is accompanied by a decrease in glutamate formation and in the maximum activity of glutaminase. Isolated incubated colonocytes utilized acetoacetate at about 3.5 mumol/min per g dry wt. This rate was not markedly affected by addition of glucose or by starvation of the donor animal. When colonocytes were incubated with n-butyrate, both acetoacetate and 3-hydroxybutyrate were formed, with the latter accounting for only about 19% of total ketones produced.
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PMID:Fuel utilization in colonocytes of the rat. 407 34

The metabolic response to the first fast experienced by all mammals has been studied in the newborn rat. Levels of fuels and hormones have been compared in the fetal and maternal circulations at term. Then, after cesarean section just before the normal time of birth, sequential changes in the same parameters were quantified during the first 16 h of the neonatal period. No caloric intake was permitted, and the newborns were maintained at 37 degrees C. Activities of three key hepatic enzymes involved in glucose production were estimated. Marked differences in maternal and fetal hormones and fuels were observed. Lower levels of glucose, free fatty acids, and glycerol but higher levels of lactate, alpha-amino nitrogen, alanine, and glutamine were present in the fetus. Pyruvate, glutamate, and ketone bodies were not significantly different. The combination of a strikingly higher fetal immunoreactive insulin and a slightly lower immunoreactive glucagon (pancreatic) resulted in a profound elevation in the insulin-to-glucagon ratio, a finding consistent with an organism in an anabolic state. The rat at birth presents a body composition with respect to fuels available for mobilization and conversion which is dominated by carbohydrate and protein, since little fat is present. However, at birth a transient period of hypoglycemia occurred, associated with a rapid fall in insulin and rise in glucagon, causing reversal of the insulin-to-glucagon relationship toward ratios such as were observed in the mother. After a lag period, hepatic activities of phosphorylase, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase increased. Concurrent with these enzyme changes, the blood glucose returned to levels at or above those of the fetus. Interestingly, the fall observed in levels of the gluconeogenic precursors, lactate and amino acids, preceded the rise in enzyme activities and restoration of blood glucose. After 4 h, however, hypoglycemia recurred, during a period of decreasing hepatic glycogen content and blood lactate, pyruvate, and glycerol levels but of stable or increasing amino acid concentrations. Hepatic gluconeogenesis in this phase of depleted glycogen stores was insufficient to maintain euglycemia. Substrates derived from fat showed early changes of smaller magnitude. The rise in free fatty acids which occurred was less than twofold the value at birth, though this rise persisted up to 6 h. Whereas glycerol rose transiently, acetoacetate did not change and beta-hydroxybutyrate concentration fell. Both ketone bodies showed a marked rise at 16 h. at a time of diminished free fatty acid levels. Plasma growth hormone, though higher in the fetal than the maternal circulation, showed no consistent change during the period of observation. The changes in levels of the endocrine pancreatic hormones at birth were appropriate in time, magnitude, and direction to be implicated as prime regulators of the metabolic response during the neonatal period in the rat.
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PMID:Fuels, hormones, and liver metabolism at term and during the early postnatal period in the rat. 475 Apr 49

The subcellular localization of glutamine synthetase, an enzyme fundamental to the compartmentation of glutamate hypothesis, was investigated using brain tissue of adult rats. The distribution of this enzyme in relation to the distribution of glucose-6-phosphatase, glutamate dehydrogenase and acetycholine esterase was studied using a fractionation scheme which had been previously extensively characterized in terms of intramitochondrial enzyme complements. Glutamine synthetase was found to be predominantly localized at the nerve terminal and a number of results suggested a possibble association with the synaptic membrane. The observations are discussed in relation to the compartmentation of glutamate metabolism. Acetate and ammonia are precursors of the 'small' pool of glutamate from which most of the synthesis of glutamine occurs. Since one population of synaptic mitochondria has previously been shown to be enriched in glutamate dehydrogenase and acetyl CoA synthetase and in view of the current observtions that synaptosomes are probably in association with a large proportion of brain glutamine synthetase, it is tentatively suggested that the synaptic complex represents at least in part the site of the 'small' glutamate pool.
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PMID:The distribution of glutamine synthetase in subcellular fractions of rat brain. 610 1

Recently there has been an increased interest in the toxic effects from long term exposure of low levels of cadmium (Cd) in diet. Male, Sprague-Dawley rats were treated with 0, 25, 50, 75 ppm Cd mixed in diet continuously for 180 days. A significant decrease in body weight gain was observed in all Cd treated animals. Serum glucose, serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvic transaminase (SGPT) were increased parallel to Cd concentration and treatment time. Measured hepatic and renal gluconeogenic enzymes, viz. glucose-6-phosphatase, fructose-1, 6-bisphosphatase and phosphoenolpyruvate carboxykinase were increased with higher Cd dose and time. Low concentration of Cd (25 ppm) had minimal effect with shorter treatment length. Fructose-1, 6-bisphosphatase was found to be very sensitive for assessing Cd-induced nephrotoxicity. Increased serum glucose level and gluconeogenic enzyme activities suggest that Cd might interfere in protein metabolism.
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PMID:Chronic hepatic and renal toxicity by cadmium in rats. 632 37

The effect of 2-aminobicyclo[2.2.1]heptan-2-carboxylic acid (BCH), an L-leucine nonmetabolizable analogue and an allosteric activator of glutamate dehydrogenase, on glucose and glutamine synthesis was studied in rabbit renal tubules incubated with alanine, aspartate or proline in the presence of glycerol and octanoate, i.e. under conditions of efficient glucose formation. With alanine+glycerol+octanoate the addition of BCH resulted in a stimulation of alanine and glycerol consumption, accompanied by an increased glucose, lactate and glutamine synthesis. In contrast, when alanine was substituted by either aspartate or proline, BCH altered neither glucose formation nor glutamine and glutamate synthesis, while an accelerated glycerol utilization was accompanied by a small increase in lactate production. In view of the BCH-induced changes in intracellular metabolite levels the acceleration of gluconeogenesis by BCH in the presence of alanine+glycerol+octanoate is probably due to (i) increased uptake of alanine via alanine aminotransferase, (ii) stimulation of phosphoenolpyruvate carboxykinase, a key-enzyme of gluconeogenesis, (iii) rise of glucose-6-phosphatase activity, as well as (iv) activation of the malate-aspartate shuttle resulting in an augmented glycerol utilization for lactate and glucose synthesis.
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PMID:Importance of glutamate dehydrogenase stimulation for glucose and glutamine synthesis in rabbit renal tubules incubated with various amino acids. 991 11

Administration of aflatoxin B1 to rats (2 mg/kg intraperitoneally) caused significant increase in the activities of gamma-glutamyl transpeptidase, 5'-nucleotidase, acid phosphatase, acid ribonuclease as well as content of lipid peroxides in liver after six weeks. However, the activities of succinate dehydrogenase, glucose-6-phosphatase, catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase and glutathione reductase in liver were decreased. The levels of glycogen and reduced glutathione were also decreased. There were significant elevations in the levels of serum transaminases, phosphatases (acid and alkaline), dehydrogenases (sorbitol, lactate and glutamate) and bilirubin following aflatoxin B1 administration. Picroliv (25 mg/kg/day orally for six weeks), an iridoid glycoside isolated from the roots and rhizomes of Picrorhiza kurroa, significantly prevented the biochemical changes induced by aflatoxin B1.
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PMID:Biochemical changes induced in liver and serum of aflatoxin B1-treated male wistar rats: preventive effect of picroliv. 1116 62

Long-term caloric restriction (CR) has been shown to extend maximum life span in laboratory rodents. We investigated the activities of gluconeogenic and transaminase enzymes in the livers of old and young mice fed either control or calorie-restricted diets. Livers were sampled 48 h after the last scheduled feeding time. Old mice on CR showed significant increases in the activities of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase and glucose-6-phosphatase when compared with controls, indicating increased gluconeogenesis. Increased activities of tyrosine, tryptophan, histidine, phenylalanine, alanine and aspartate transaminases, as well as of malate and glutamate dehydrogenases were also observed, while branched-chain amino acid transaminase was unchanged. Young mice on CR showed a significant increase only in the phosphoenolpyruvate carboxykinase activity in the gluconeogenic pathway, while transaminases were increased significantly, except for tryptophan and branched-chain amino acid transaminases. Glutamate dehydrogenase also showed increased activity but malate dehydrogenase was unchanged. Increases in the level of acetyl-CoA and [Acetyl-CoA]/[CoA] ratio were observed only in the old CR mice. Our results demonstrate increased gluconeogenic activity in CR mice and are consistent with a state of increased hepatic gluconeogenesis and protein turnover during CR.
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PMID:Caloric restriction increases gluconeogenic and transaminase enzyme activities in mouse liver. 1258 90


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