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

Four cytoplasmically synthesized rat liver mitochondrial enzymes, located either as soluble enzymes in the mitochondrial matrix (L-glutamate dehydrogenase and malate dehydrogenase or in the intermembrane space (sulfite oxidase) or as an integral membrane protein located on the matrix face of the inner mitochondrial membrane (D-beta-hydroxybutyrate dehydrogenase), were all shown to be synthesized as precursors larger than their mature counterparts by 1000-6000 daltons. These larger forms were detected in vitro, in a cell-free protein synthesizing system programmed with either total rat liver RNA or with RNA isolated from free polysomes or with free polysomes, and in vivo, in the two cases that were investigated (L-glutamate dehydrogenase and D-beta-hydroxybutyrate dehydrogenase), by pulse labeling of Buffalo rat liver cells in culture. The intracellular site of synthesis of all four mitochondrial enzymes was shown to be primarily on free polysomes and not on membrane-bound polysomes.
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PMID:Rat liver L-glutamate dehydrogenase, malate dehydrogenase, D-beta-hydroxybutyrate dehydrogenase, and sulfite oxidase are each synthesized as larger precursors by cytoplasmic free polysomes. 706 82

To investigate the mechanisms of the antiammoniagenic effect of ketone bodies, acidotic dogs (NH4Cl) were infused with either beta-hydroxybutyrate or acetoacetate. Total blood ketones ranged from 2 to 4 mM. Renal ammoniagenesis fell by a mean of 53%, with a proportional decrease in glutamine extraction. Glutamate release in the renal vein rose, renal extraction of lactate fell, and aspartate and alanine production decreased. Study of the metabolite profile of the renal cortex by the freeze-clamp technique before and after ketone infusion showed that tissue glutamine concentration was unchanged, whereas glutamate, alpha-ketoglutarate, malate, and citrate rose. The intermediates of the gluconeogenic pathway, such as phosphoenolypyruvate, 2-phosphoglycerate, 3-phosphoglycerate, and glucose-6-phosphate, fell significantly. The redox state as calculated from the free NAD+/NADH ratios in the cytosolic (lactate dehydrogenase) and the mitochondrial (glutamate dehydrogenase and beta-hydroxybutyrate dehydrogenase) compartments was reduced. The present study suggests that ketone bodies inhibit renal ammoniagenesis through increased generation of alpha-ketoglutarate (metabolic or bicarbonate effect) and a decrease in the mitochondrial and cytosolic redox potentials in the kidney.
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PMID:Cellular mechanisms of the antiammoniagenic effect of ketone bodies in the dog. 743 17

1. Protein-free extracts of isolated rat-liver mitochondria contain 5.17 +/- 0.19 nmol ammonia/mg protein [cf. Harris, E. J. and Bassett, D. J. (1971) FEBS Lett. 19, 214-217]. 2. The ammonia found in the protein-free extracts does not originate from lysosomes contaminating the mitochondrial preparation. 3. When isolated mitochondria are incubated with ornithine, 14CO2 and a source of ATP a small amount of citrulline is formed. This amount is stoichiometrically equivalent to the ammonia that disappears from the extramitochondrial space, whereas the amount of ammonia found in the protein-free extracts of the mitochondria remains unchanged. Similar results were obtained when the reductive amination of 2-oxoglutarate was used as an ammonia-consuming reaction. 4. When isolated mitochondria are incubated under conditions such that the glutamate dehydrogenase and 3-hydroxybutyrate dehydrogenase reactions reach equilibrium, the thermodynamically active concentration of ammonia is not equal to the concentration measured in the protein-free extracts. 5. About 80% of the ammonia found in protein-free extracts of rat-liver mitochondria is derived from a component or components with a molecular weight of greater than or equal to 50,000. 6. Protein-free extracts of isolated rat-liver cells contain considerable amounts of ammonia. After digitonin fractionation this ammonia is found in the protein-free extract of the particulate fraction. 7. It is concluded that the ammonia found in protein-free extracts of rat-liver tissue is derived from a component or components in the mitochondria and is released during deproteinization.
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PMID:Origin of the ammonia found in protein-free extracts of rat-liver mitochondria and rat hepatocytes. 743 58

The model of hyperenzymia caused by injection of lactate dehydrogenase (5000 U/kg body weight) causes an increase of NADP.H-dependent oxidation in liver microsomes, without changing oxidative intensity in mitochondria, by such NAD.H-depended dehydrogenases as glutamate dehydrogenase and beta-hydroxybutyrate dehydrogenase. The aim of the interaction with exogenous lactate dehydrogenase in the glycolytic metabolone system, where increased carbohydrate disintegration in vivo is induced. There is a high detoxification processes associated with ammonia detoxification and urea production. The stability of membrane permeability is characterized by the absence of glutamate dehydrogenase and glucoso-6-phosphate dehydrogenase activity in blood plasma. It has been shown that the introduction of exogenic lactate dehydrogenase into the metabolism of experimental animals gives the possibility of using this enzyme as an enzymotherapeutic remedy.
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PMID:[The modelling of hyperfermentemia--a method for studying the mechanisms of the formation of metabolic disorders]. 811 55

Anterograde or retrograde perfusion of rat liver with digitonin selectively permeabilizes the periportal or the perivenous zone of the hepatic lobule. Digitonin perfusion is used to analyze the effluents released by permeabilized hepatocytes or, combined with collagenase perfusion, to obtain cell suspensions enriched in either periportal or perivenous hepatocytes. Despite the wide use of digitonin to study lobular heterogeneity, its affects on rat hepatocytes are not well documented. We therefore analyzed the effects of digitonin perfusion on the intracellular content of rat hepatocytes by combining electron microscopy, histoenzymology, immunohistochemistry, and in situ hybridization. At the concentration currently used for the study of lobular heterogeneity, digitonin perfusion induced a marked cytosolic clarification of permeabilized hepatocytes, while most organelles except mitochondria were well preserved. In the digitonin-altered zones, there was no histochemical detection of non-membrane-bound enzymes (lactate dehydrogenase, glutamate dehydrogenase), whereas membrane-bound enzymes (succinate dehydrogenase, beta-hydroxybutyrate dehydrogenase, NADPH dehydrogenase, glucose-6-phosphatase) were still detected. Immunohistochemistry and in situ hybridization revealed significant amounts of several plasma proteins (albumin, alpha 2-macroglobulin, alpha 1-inhibitor 3, alpha 1-acid glycoprotein) and their respective mRNAs in digitonin-permeabilized hepatocytes. The demonstration that digitonin-permeabilized hepatocytes retain many intracellular constituents shows that biochemical analysis of cellular effluents released from digitonin-permeabilized hepatocytes must be interpreted with caution and that the apparent characteristics of cell suspensions obtained by the digitonin-collagenase technique might be significantly altered by contamination with permeabilized hepatocytes from the opposite zone.
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PMID:Effects of digitonin on the intracellular content of rat hepatocytes: implications for its use in the study of intralobular heterogeneity. 815 38

Little is known about the alterations of metabolic organization of the human liver tissue in chronic liver diseases. We therefore compared the distribution of the following zonal metabolic markers in 10 samples of normal liver tissue, 10 samples of fibrotic tissue, and 22 samples of cirrhotic tissue: (a) the enzymatic activities of glucose-6-phosphatase (G6P), lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), nicotinamide-adenine-dinucleotide-phosphate [NAPH] dehydrogenase (ND), beta-hydroxybutyrate dehydrogenase (HBDH), and glutamate dehydrogenase (GDH); (b) the protein glutamine synthetase (GLS); and (c) albumin messenger RNA (mRNA). The normal human hepatic lobule was characterized by the periportal predominance of G6P and SDH enzymatic activities and albumin mRNAs, the perivenous predominance of ND and GDH, the restriction of GLS to a small perivenous compartment, and the predominanc of beta-HBDH at the contact of both portal tracts and centrilobular veins. In fibrosis, the overall metabolic organization of the normal liver tissue was retained. The expression of periportal markers predominated around enlarged portal tracts and that of perivenous markers around residual centrilobular veins. GLS was constantly detected at the contact of centrilobular veins. In cirrhotic nodules, no zonation was observed for most enzymatic activities or for albumin. Only G6P usually predominated at the periphery of the nodules. GLS was constantly undetectable. No difference accordingly to the etiology of the underlying disease was observed. In conclusion, the normal human hepatic lobule presents a marked metabolic zonation, preserved in fibrotic lesions, but lost in cirrhotic nodules. The alterations of the metabolic organization observed in cirrhosis might contribute to the pathogenesis of some of the metabolic disorders associated with advanced liver disease.
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PMID:The metabolic organization of the adult human liver: a comparative study of normal, fibrotic, and cirrhotic liver tissue. 870 47

The coexpression of normally periportal and perivenous markers has been described in heterotopically transplanted hepatocytes. To determine whether such a coexpression might also occur in hepatocytes retaining their original intrahepatic location, we compared in bile-duct-ligated livers and intrasplenically transplanted hepatocytes, the expression and distribution of the predominantly periportal glucose-phosphatase, succinate dehydrogenase, and lactate dehydrogenase, the predominantly perivenous glutamate dehydrogenase, NADPH-dehydrogenase, and beta-hydroxybutyrate dehydrogenase, and the strictly perivenous glutamine synthetase. The coexpression of high levels of the two periportal markers glucose-6-phosphatase and lactate dehydrogenase and of the perivenous marker NADPH dehydrogenase was observed in two situations: in clusters of hepatocytes isolated within the ductular proliferation in bile-duct-ligated livers and the majority of intrasplenically transplanted hepatocytes. The expression of glutamine synthetase was different according to the site. The protein was observed in certain intrasplenically transplanted hepatocytes bordering the splenic vessels but was never detected in hepatocyte clusters found in bile-duct-ligated livers. Our study therefore suggests that the coexpression of periportal and perivenous markers in the same hepatocytes is likely to be a non-specific consequence of the loss of the normal connections of hepatocytes with the normal liver microcirculation.
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PMID:Coexpression of periportal and perivenous enzymes in rat hepatocytes after experimental bile duct ligation: comparison with intrasplenically transplanted hepatocytes. 907 88

The specific activities of D-3-hydroxybutyrate dehydrogenase (BDH) and glutamate dehydrogenase (GDH) are reduced in the liver and kidney of rats intoxicated with 2.5 mg Cd/kg body wt and sacrificed after 24 h; conversely ketone-body concentration is strongly increased in both of these organs and blood. In the same animals a great stimulation of antioxidant enzymes glutathione reductase and glutathione peroxidase occurs. The prooxidant state induced by cadmium in liver mitochondria and microsomes is unaffected by superoxide dismutase, catalase, or mannitol, whereas it is completely blocked by vitamin E thus excluding the involvement of reactive oxygen species in this process. The mechanism by which cadmium induces lipid peroxidation has been investigated by measuring the effect of this metal on liposomes. Ninety-minute treatment of liposomes with CdCl2 does not induce any lipid peroxidation. In contrast, Fe2+ ions under the same conditions cause strong liposome peroxidation. It has also been observed that cadmium promotes a time-dependent iron release from biological membranes. When lipid peroxidation is induced by a low concentration (5 microM) of FeCl2, in place of CdCl2, the characteristics of this process and the sensitivity to the various antioxidants used are similar to those observed with Cd. From these results we conclude that the prooxidative effect of cadmium is an indirect one since it is mediated by iron. With regard to the inhibitory effect on BDH and GDH following cadmium intoxication, it does not appear to be imputable to lipid peroxidation since in vitro investigations indicate that the presence of vitamin E does not remove the inhibition at all.
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PMID:Enzyme activity alteration by cadmium administration to rats: the possibility of iron involvement in lipid peroxidation. 934 63

Trigonella foenum graecum is a well-known hypoglycemic agent used in traditional Indian medicines. It was previously reported that oral administration of its seed powder for 3 weeks to alloxan diabetic rats stabilized glucose homeostasis and free radical metabolism in liver and kidney. In the present study, we further investigated the effects of 3 weeks alloxan induced diabetes on the histological structure and function of liver and kidney and the protective effect of T. foenum graecum seed powder (TSP) oral administration to the diabetic rats utilizing enzyme analysis and light and transmission electron microscopy. The activity of the enzyme, glutamate dehydrogenase was significantly higher whereas the activity of D-beta-hydroxybutyrate dehydrogenase enzyme was significantly lower in liver and kidney of alloxan-induced diabetic rats. Histopathological studies showed liver degenerative and early nephropathic changes in diabetic rats. Ultrastructure of the diabetic liver revealed a reduction in the rough endoplasmic reticulum and swelling of mitochondria in the hepatocytes. TSP treatment to the diabetic rats effectively prevented the alteration in the activities of the two enzymes and partially prevented the structural abnormalities thus suggesting a protective effect of TSP on the liver and kidney of the diabetic rats. The role of TSP in reversing the diabetic state at the cellular level besides the metabolic normalization further proves its potential as an antidiabetic agent.
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PMID:Trigonella foenum graecum seed powder protects against histopathological abnormalities in tissues of diabetic rats. 1564 37

To test the hypothesis that the preference for ketone bodies rather than lipids as oxidative fuel in elasmobranchs evolved in response to the appearance of urea-based osmoregulation, we measured total non-esterified fatty acids (NEFA) in plasma as well as maximal activities of enzymes of intermediary metabolism in tissues from marine and freshwater elasmobranchs, including: the river stingray Potamotrygon motoro (<1 mmol l(-1) plasma urea); the marine stingray Taeniura lymma, and the marine shark Chiloscyllium punctatum (>300 mmol l(-1) plasma urea); and the euryhaline freshwater stingray Himantura signifer, which possesses intermediate levels of urea. H. signifer also were acclimated to half-strength seawater (15 per thousand) for 2 weeks to ascertain the metabolic effects of the higher urea level that results from salinity acclimation. Our results do not support the urea hypothesis. Enzyme activities and plasma NEFA in salinity-challenged H. signifer were largely unchanged from the freshwater controls, and the freshwater elasmobranchs did not show an enhanced capacity for extrahepatic lipid oxidation relative to the marine species. Importantly, and contrary to previous studies, extrahepatic lipid oxidation does occur in elasmobranchs, based on high carnitine palmitoyl transferase (CPT) activities in kidney and rectal gland. Heart CPT in the stingrays was detectable but low, indicating some capacity for lipid oxidation. CPT was undetectable in red muscle, and almost undetectable in heart, from C. punctatum as well as in white muscle from T. lymma. We propose a revised model of tissue-specific lipid oxidation in elasmobranchs, with high levels in liver, kidney and rectal gland, low or undetectable levels in heart, and none in red or white muscle. Plasma NEFA levels were low in all species, as previously noted in elasmobranchs. D-beta-hydroxybutyrate dehydrogenase (d-beta-HBDH) was high in most tissues confirming the importance of ketone bodies in elasmobranchs. However, very low d-beta-HBDH in kidney from T. lymma indicates that interspecific variability in ketone body utilization occurs. A negative relationship was observed across species between liver glutamate dehydrogenase activity and tissue or plasma urea levels, suggesting that glutamate is preferentially deaminated in freshwater elasmobranchs because it does not need to be shunted to urea production as in marine elasmobranchs.
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PMID:Metabolic organization of freshwater, euryhaline, and marine elasmobranchs: implications for the evolution of energy metabolism in sharks and rays. 1678 33


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