Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.4.1.2 (glutamate dehydrogenase)
 4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression patterns of the mRNAs for the ammonia-metabolizing enzymes carbamoylphosphate synthetase (CPS), glutamine synthetase (GS) and glutamate dehydrogenase (GDH) were studied in developing pre- and neonatal rat liver by in situ hybridization. In the period of 11 to 14 embryonic days (ED) the concentrations of GS and GDH mRNA increases rapidly in the liver, whereas a substantial rise of CPS mRNA in the liver does not occur until ED 18. Hepatocyte heterogeneity related to the vascular architecture can first be observed at ED 18 for GS mRNA, at ED 20 for GDH mRNA and three days after birth for CPS mRNA. The adult phenotype is gradually established during the second neonatal week, i.e. GS mRNA becomes confined to a pericentral compartment of one to two hepatocytes thickness, CPS mRNA to a large periportal compartment being no longer expressed in the pericentral compartment and GDH mRNA is expressed over the entire porto-central distance, decreasing in concentration going from central to portal. Comparison of the observed mRNA distribution patterns in the perinatal liver, with published data on the distribution of the respective proteins, points to the occurrence of posttranslational, in addition to pretranslational control mechanisms in the period of ontogenesis of hepatocyte heterogeneity. Interestingly, during development all three mRNAS are expressed outside the liver to a considerable extent and in a highly specific way, indicating that several organs are involved in the developmentally regulated expression of the mRNAs for the ammonia-metabolizing enzymes, that were hitherto not recognized as such.
 ...
PMID:Expression patterns of mRNAs for ammonia-metabolizing enzymes in the developing rat: the ontogenesis of hepatocyte heterogeneity. 197 81

Proteins characteristic for the adult cellular phenotype, i.e., carbamoylphosphate synthetase (CPS) for liver and small intestine, arginase for liver, glutamate dehydrogenase (GLDH) for pancreas, liver, and small intestine, and amylase for pancreas were studied immunohistochemically in rat embryos and fetuses. At distinct developmental stages, subsets of enzymes appear synchronously in the foregut derivatives, suggesting that gene expression in the different organs is regulated by common factors. In contrast to the long-held opinion that fetal hepatocytes are a homogeneous cell population, it is shown that arginase and CPS are heterogeneously distributed between ED 16 and ED 20. This heterogeneity is related to the vascular architecture of the liver and disappears perinatally as the result of strong stimulation of enzyme synthesis. In addition, an intercellular heterogeneity in CPS content that is not related to the vasculature is observed between ED 14 and ED 20. This "random" heterogeneity reflects temporal differences in the onset of CPS accumulation in individual cells.
 ...
PMID:Gene expression in derivatives of embryonic foregut during prenatal development of the rat. 245 6

In monolayer cultures, hepatocyte-specific enzymes are inducible by hormones as soon as hepatocytes differentiate from the embryonic foregut (15-somite stage). Though offering an excellent opportunity for quantitative studies, several features of a normal cell environment are lost in such a model system. To determine the inducibility of such tissue-specific enzymes in intact organisms, rat embryos were cultured in vitro for 48 h and exposed to the hormonal factors that had been found effective in monolayer culture, viz. dexamethasone, triiodothyronine and dibutyryl cyclic AMP. Normal development of the embryos during culture in vitro was assessed by general criteria reflecting growth, morphogenesis and cytodifferentiation. Development of external features, organogenesis, the distribution of cell divisions and the appearance of tissue-specific proteins such as alpha-fetoprotein and glutamate dehydrogenase served as parameters. Despite undisturbed development of the embryos as judged by these criteria, irrespective of whether the culture was started at day 10 or at day 11 of gestation (just before, respectively after the appearance of the liver primordium), induction of hepatocyte-specific enzymes like carbamoylphosphate synthetase by hormones could not be demonstrated immunohistochemically. However, induction of this enzyme by hormones could be demonstrated in monolayers of hepatocytes isolated from such embryos after 48 h of culture, providing yet another demonstration of the adequate culture conditions. In addition, an adequate uptake of hormones by the embryo during culture could be shown with radio-actively labeled dexamethasone and triiodothyronine and with a radioreceptor assay for cyclic AMP. Therefore, the presence of factors in young embryos that inhibit tissue-specific enzyme synthesis has to be postulated.
 ...
PMID:Hormonal inducibility of liver-specific enzymes in cultured rat embryos. 282 35

The appearance of the distribution patterns of the NH3-metabolizing enzymes carbamoylphosphate synthetase, glutamate dehydrogenase, and glutamine synthetase in the developing liver of an altricial species (rat) was compared with that in the developing liver of a closely related, precocial species (spiny mouse). The comparison showed that the development of hepatic acinar architecture, rather than perinatal adaptation, is responsible for the development of periportal and pericentral compartments of gene expression. Conditions that confine the expression of specific enzymes to the pericentral compartment of the acinus originate before conditions that confine the expression of (other) specific enzymes to the periportal compartment. However, whether or not the site of gene expression is restricted to specific compartments within the liver acinus, the rate of expression of the gene involved can also be adaptively regulated. Therefore, different factors appear to control the site and the rate of gene expression within one tissue.
 ...
PMID:Development of enzymic zonation in liver parenchyma is related to development of acinar architecture. 289 21

In adult rat liver, glutamate dehydrogenase is present in high concentrations around the terminal portal (zone 1) and hepatic (zone 3) veins, whereas its concentration is low in the intermediate zone. Although the size and staining intensity of the periportal glutamate dehydrogenase-positive compartment are less than those of the pericentral compartment, it can expand under appropriate endocrine conditions, leading to a homogeneous distribution. At birth, glutamate dehydrogenase is also homogeneously distributed. Glutamate dehydrogenase disappears from the periportal compartment during the first postnatal week and reappears in that compartment after weaning. These observations indicate an independent regulation of glutamate dehydrogenase levels in the periportal and pericentral zone. The size of the periportal glutamate dehydrogenase-containing zone is appreciably smaller than that of carbamoylphosphate synthetase, whereas the pericentral glutamate dehydrogenase-containing zone is appreciably larger than that of glutamine synthetase. The heterogeneous distribution of glutamate dehydrogenase suggests the possibility that, under normal conditions, deamination of glutamate prevails in the periportal compartment and amination of glutamate in the pericentral compartment.
 ...
PMID:Immunohistochemical localization of glutamate dehydrogenase in rat liver: plasticity of distribution during development and with hormone treatment. 333 69

Xenopus laevis was adapted stepwise to 600 m osmolar sodium chloride. After adaptation, the level of argininosuccinate lyase was raised 9-fold, carbamoylphosphate synthetase 6-fold, and ornithine carbamoyltransferase and arginase 3-fold. Liver glutamate dehydrogenase was also raised 5-fold; kidney glutamate dehydrogenase was unchanged. In Bufo viridis similarly adapted, there was a 5-fold increase in argininosuccinate lyase. When Xenopus laevis was adapted to 600 m osmolar sucrose, there was only an increase in argininosuccinate lyase, and that was only 2.4-fold. This indicates that the increases in urea cycle enzymes are at least in part responses to sodium chloride rather than just to osmotic stress.
 ...
PMID:Urea cycle enzymes and glutamate dehydrogenase in Xenopus laevis and Bufo viridis adapted to high salinity. 709 81

The liver is the major site of gluconeogenesis, the major organ of amino acid catabolism and the only organ with a complete urea cycle. These metabolic capabilities are related, and these relationships are best exemplified by an examination of the disposal of the daily protein load. Adults, ingesting a typical Western diet, will consume approximately 100 g protein/d; the great bulk of this is metabolized by the liver. Although textbooks suggest that these amino acids are oxidized in the liver, total oxidation cannot occur within the confines of hepatic oxygen uptake and ATP homeostasis. Rather, most amino acids are oxidized only partially in the liver, with the bulk of their carbon skeleton being converted to glucose. The nitrogen is converted to urea and, to a lesser extent, to glutamine. The integration of the urea cycle with gluconeogenesis ensures that the bulk of the reducing power (NADH) required in the cytosol for gluconeogenesis can be provided by ancillary reactions of the urea cycle. Glutamate is at the center of these metabolic events for three reasons. First, through the well-described transdeamination system involving aminotransferases and glutamate dehydrogenase, glutamate plays a key catalytic role in the removal of alpha-amino nitrogen from amino acids. Second, the "glutamate family" of amino acids (arginine, ornithine, proline, histidine and glutamine) require the conversion of these amino acids to glutamate for their metabolic disposal. Third, glutamate serves as substrate for the synthesis of N-acetylglutamate, an essential allosteric activator of carbamyl phosphate synthetase I, a key regulatory enzyme in the urea cycle.
 ...
PMID:Glutamate, at the interface between amino acid and carbohydrate metabolism. 1073 67

Influence of alimentary zinc deficiency on nitrogen elimination and activities of urea cycle enzymes This study was conducted to investigate whether the hyperammonaemia shown in earlier zinc-deficiency experiments was the result of disturbed enzyme activities of the urea cycle. For this study 36 male Sprague-Dawley rats with an average body weight of 85 g were divided into three experimental groups of 12 animals each. Group 1 received the semisynthetic zinc-deficient diet (AIN-93G; 1.2 mg Zn/kg DM) ad libitum over 33 experimental days. Group 2 received the zinc-sulphate-supplemented control diet (60 mg Zn/kg DM) ad libitum and group 3 received the same diet matched to the feed intake of the zinc-deficient rats. Alimentary zinc deficiency reduced the zinc concentration and the activity of the alkaline phosphatase in serum by 75 and 67%, respectively. The activity of the glutamate dehydrogenase and the concentrations of ammonia and urea in the serum of the zinc-deficient rats showed no significant differences compared with pair-fed control rats. On the other hand the hepatic activity of the mitochondrial localized glutamate dehydrogenase of the zinc-deficient rats was significantly increased and the carbamoylphosphate synthetase and ornithine carbamoyltransferase were reduced about half in comparison with both control groups. The activities of the cytosolic liver enzymes such as argininosuccinate synthetase, argininosuccinase and arginase were again significantly increased in zinc-deficient rats compared with both control groups. The increased hepatic activity of the glutamate dehydrogenase possibly led to an enhanced NH(3) elimination in addition to urea synthesis. The typical reduction of feed intake in consequence of zinc deficiency is therefore not the cause of hyperammonaemia due to disturbed urea synthesis, as has been hypothesized in earlier studies.
 ...
PMID:[Influence of alimentary zinc deficiency on nitrogen elimination and enzyme activities of the urea cycle]. 1168 72

The aim of this investigation was to determine if the hyperammonaemia shown in previous zinc-deficiency experiments was the result of disturbed enzyme activities for urea synthesis caused by zinc deficiency per se or was a secondary effect of the reduced feed intake accompanying energy and protein deficiency. For this, 24 male Sprague-Dawley rats with an average body weight of 109 g were divided into two groups of 12 animals each. Both groups were force fed by intragastric tube four times daily over 11 experimental days. Group 1 received a zinc-deficient diet (1.3 mg Zn/kg diet) in a total amount of 11.6 g/day/animal. Group 2 received the zinc sulphate-supplemented control diet (25 mg Zn/kg diet) in the same amount. This technique made it possible to supply even the zinc-deficient rats with sufficient nutrients over the whole experimental period in the same manner as for the control rats, at the same time and with the same dietary amounts. At the end of the experiment, the serum zinc concentration and the alkaline phosphatase activity were significantly reduced in the zinc-deficient rats by 59 and 37%, respectively, in comparison with control animals. This showed a severe alimentary zinc-deficiency status of the animals. The concentrations of ammonia and urea, as well as the activity of glutamate dehydrogenase in serum, were not influenced by the zinc-deficient nutrition within the experimental time. Likewise, the mitochondrial activities of glutamate dehydrogenase and carbamoylphosphate synthetase in the liver were not affected by the alimentary zinc concentration. On the contrary, the activities of ornithine carbamoyltransferase and cytosolic liver enzymes argininosuccinate synthetase, argininosuccinase and arginase were significantly increased in comparison with control rats. In the case of a sufficient supply of nutrients, alimentary zinc deficiency did not cause hyperammonaemia owing to disturbed urea synthesis, as previously hypothesized.
 ...
PMID:[Nitrogen detoxification in artificially-fed zinc-deficient rats]. 1168 84

The aim of the present study was to determine whether the level of dietary protein would influence the onset of zinc deficiency in rats because zinc-deprived rats have problems metabolizing dietary protein. Young male Sprague-Dawley rats were fed isoenergetic Zn-deficient diets (0.8 mg Zn/kg diet) or control diets substituted with zinc sulfate (54 mg Zn/kg diet) and protein levels of 2, 5, 8, 10, 15, 20 or 25 g/100 g for 21 d to determine whether changing the protein level of Zn-deficient diets affects the Zn status of the rats. In rats fed low dietary protein levels of 2 and 5%, feed intake, growth and appearance did not differ between the Zn-deficient rats and the control rats because the low zinc requirement was met by mobilization of zinc from the skeleton. At higher dietary protein levels, the Zn-depleted rats developed marked signs of Zn deficiency and had reduced feed intake, growth, alkaline phosphatase activity in the serum and Zn concentrations in serum and femur compared with the control rats. The reduced feed intakes and decreased growth of Zn-depleted rats fed high dietary protein levels (20 and 25%) compared with control rats may be due to disturbed protein synthesis, as demonstrated by the increased activities of alanine aminotransferase, glutamate dehydrogenase and carbamoylphosphate synthetase in the liver. Zinc as an essential component of the diet is thus vital for the efficient utilization of dietary protein.
 ...
PMID:Development of alimentary zinc deficiency in growing rats is retarded at low dietary protein levels. 1284 Jan 96


1 2 Next >>