Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.32 (phosphoenolpyruvate carboxykinase)
 4,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolism of proline was studied in liver cells isolated from starved rats. The following observations were made. 1. Consumption of proline could be largely accounted for by production of glucose, urea, glutamate and glutamine. 2. At least 50% of the total consumption of oxygen was used for proline catabolism. 3. Ureogenesis and gluconeogenesis from proline could be stimulated by partial uncoupling of oxidative phosphorylation. 4. Addition of ethanol had little effect on either proline uptake or oxygen consumption, but strongly inhibited the production of both urea and glucose and caused further accumulation of glutamate and lactate. Accumulation of glutamine was not affected by ethanol. 5. The effects of ethanol could be overcome by partial uncoupling of oxidative phosphorylation. 6. The apparent K(m) values of argininosuccinate synthetase (EC 6.3.4.5) for aspartate and citrulline in the intact hepatocyte are higher than those reported for the isolated enzyme. 7. 3-Mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase (EC 4.1.1.32), greatly enhanced cytosolic aspartate accumulation during proline metabolism, but inhibited urea synthesis. 8. It is concluded that when proline is provided as a source of nitrogen to liver cells, production of ammonia by oxidative deamination of glutamate is inhibited by the highly reduced state of the nicotinamide nucleotides within the mitochondria. 9. Conversion of proline into glucose and urea is a net-energy-yielding process, and the high state of reduction of the nicotinamide nucleotides is presumably maintained by a high phosphorylation potential. Thus when proline is present as sole substrate, the further oxidation of glutamate by glutamate dehydrogenase (EC 1.4.1.3) is limited by the rate of energy expenditure of the cell.
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PMID:Prolone metabolism in isolated rat liver cells. 64 9

Argininosuccinate synthetase and argininosuccinate lyase catalyze the conversion of citrulline to arginine in kidney. Immunohistochemical staining of mouse kidney sections with antibodies to these two enzymes, compared with the staining patterns of known markers for proximal tubules, demonstrated that these enzymes are localized within the proximal tubules. The relative abundance of mRNA encoding argininosuccinate synthetase and argininosuccinate lyase during fetal and postnatal development of mouse kidney was also determined. Changes in relative abundance of these mRNA in kidney are coordinate during development, paralleling the developmental profile of phosphoenolpyruvate carboxykinase mRNA, which is also expressed in proximal tubules. Although relative abundances of the mRNA are comparable in liver and kidney of adult mice, the profiles of mRNA abundance during development of these two organs are distinct. The results indicate that these enzymes and their corresponding mRNA can serve as useful markers for examining the differentiation and development of renal proximal tubules in vivo and in cultured explants.
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PMID:Localization of arginine biosynthetic enzymes in renal proximal tubules and abundance of mRNA during development. 201 50

Somatic cell hybrids formed by fusing hepatoma cells with fibroblasts generally fail to express liver functions, a phenomenon termed extinction. Previous studies demonstrated that extinction of the genes encoding tyrosine aminotransferase, phosphoenolpyruvate carboxykinase, and argininosuccinate synthetase is mediated by a specific genetic locus (TSE1) that maps to mouse chromosome 11 and human chromosome 17. In this report, we show that full repression of these genes requires a genetic factor in addition to TSE1. This conclusion is based on the observation that residual gene activity was apparent in monochromosomal hybrids retaining human TSE1 but not in complex hybrids retaining many fibroblast chromosomes. Furthermore, TSE1-repressed genes were hormone inducible, whereas fully extinguished genes were not. Analysis of hybrid segregants indicated that genetic loci required for the complete repression phenotype were distinct from TSE1.
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PMID:Hormonal regulation of TSE1-repressed genes: evidence for multiple genetic controls in extinction. 257 Oct 76

Chromosomal deletions at and around the albino locus on chromosome 7 of the mouse affect the enzyme activities and steady-state levels of mRNAs for five urea-cycle enzymes in liver. In newborn c3H homozygotes, activities of these enzymes were 43-62% of normal, while corresponding mRNA levels were 14-29% of normal. c14CoS deletion homozygotes expressed mRNA levels for these enzymes which were 32-48% of normal. However, transcription rates of these genes in hepatic nuclei of c3H/c3H mice were reduced only to 57-84% of normal. Since effects of the deletions had previously been noted in the kidney, mRNA levels for three enzymes expressed also in the kidney were examined. Mice homozygous for the c3H deletion, shown previously to have drastically reduced mRNA levels for phosphoenolpyruvate carboxykinase in the liver, expressed the same deficiency in the kidney, while mRNA levels for argininosuccinate synthetase and argininosuccinate lyase were reduced in the liver but remained unaffected in the kidney. However, mRNA levels for phosphoenolpyruvate carboxykinase, carbamyl phosphate synthetase I, and ornithine transcarbamylase were unaffected in the intestine of c3H homozygotes. The results suggest that a regulatory factor(s) encoded in the DNA encompassed by the deletion is involved in the normal developmental maturation of hepatocytes and certain cells in the kidney.
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PMID:Effects of deletions in mouse chromosome 7 on expression of genes encoding the urea-cycle enzymes and phosphoenolpyruvate carboxykinase (GTP) in liver, kidney, and intestine. 324 91

Thyroxine-induced metamorphosis of the tadpole to the frog (Rana catesbeiana) is marked by increased activities of the urea cycle enzymes in liver. Cloned cDNAs for two mammalian urea cycle enzymes--carbamyl-phosphate synthetase I and argininosuccinate synthetase--were shown to cross-hybridize with the corresponding mRNAs in tadpole liver. Thyroxine treatment produced nearly 10-fold, coordinate increases in hybridizable mRNA levels for these two enzymes in tadpole liver. This increase is sufficient to account for reported increases in enzyme levels and synthesis rates, demonstrating that thyroxine largely regulates concentrations of these enzymes at a pretranslational step(s). In contrast, levels of phosphoenolpyruvate carboxykinase mRNA in tadpole liver decreased by more than 90% following thyroxine treatment. This differs from the thyroxine-induced increases in synthesis rates of enzyme and mRNA reported for phosphoenolpyruvate carboxykinase in rat liver. However, the decreased levels of this mRNA in tadpole liver may represent a secondary response due to thyroxine-stimulated release of insulin.
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PMID:Thyroxine elicits divergent changes in mRNA levels for two urea cycle enzymes and one gluconeogenic enzyme in tadpole liver. 350 Jun 75

Diurnal rhythms are demonstrated in five rat liver enzymes : argininosuccinate synthetase, ATP : citrate lyase, glutamate dehydrogenase, phosphoenolpyruvate carboxykinase, and succinate dehydrogenase. In a 12 : 12 h light-dark cycle, maxima of enzyme activities occur at the beginning of the dark phase in the case of phosphoenolpyruvate carboxykinase, at the end of the dark phase in ATP : citrate lyase, and in the middle of the dark phase in the other three enzymes. The diurnal increase of phosphoenolpyruvate carboxykinase is blocked by cycloheximide, cordycepin, alpha-amanitin, and 5-azacytidine. The maximum of ATP : citrate lyase is likewise suppressed at the levels of both translation and transcription, as shown by administration of cycloheximide and 5-azacytidine, respectively. Hence, these two enzymes appear to be regulated transcriptionally. The diurnal rise of argininosuccinate synthetase an glutamate dehydrogenase is also totally inhibited by cycloheximide, whereas cordycepin, alpha-amanitin, and 5-azacytidine are ineffective in the first phase of enzyme accumulation. In a later phase, however, alpha-amanitin and 5-azacytidine become inhibitory. The two enzymes therefore seem to be regulated sequentially by post-transcriptional and transcriptional mechanisms. The diurnal increase of succinate dehydrogenase is nearly insensitive to alpha-amanitin and 5-azacytidine; cycloheximide is only partially inhibitory and, in particular, almost ineffective during the late rise. Thus, the rhythm of this enzyme might be controlled mainly by an activation and, perhaps, by a transitory post-transcriptional mechanism.
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PMID:Different levels of gene realization in the diurnal control of rat liver enzymes. 617 90

In chronic renal failure (CRF), renal ammoniagenesis and handling of ornithine cycle intermediates (ornithine, citrulline, and arginine) are disturbed. The present study examined the molecular mechanisms of these disturbances in kidney and liver of rats with moderate CRF induced by 5/6 nephrectomy. The steady state level of mRNA for phosphoenolpyruvate carboxykinase (PEPCK) and argininosuccinate synthetase (ASS) in both kidney and liver were unaffected by CRF. On the other hand, that for phosphate-dependent glutaminase (PDG) was increased while that for ornithine decarboxylase (ODC) was decreased in the diseased kidney. Combined with previously reported enzymatic activities, our findings suggest that, in CRF, gene expression is responsible for enzymatic changes of PDG and ODC, not of PEPCK and ASS. Underexpression of ODC, resulting in impaired renal polyamine synthesis, may contribute to progression of CRF. Finally, the significant increase in renal mRNA expression of beta-actin precludes the use of this molecule as a reference in CRF.
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PMID:Effect of chronic renal failure on the abundance of mRNA for enzymes of intermediary metabolism in kidney and liver. 785 37

Patients with an acyl-CoA dehydrogenase deficiency share the disease features of hypoglycemia, hyperammonemia, tissue fatty change, hypoketonemia, carnitine deficiency, and organic acidemia due to apparent disruption of normal fatty acid, glucose, and urea metabolism. Most of the acute clinical episodes occur in young children. These episodes are precipitated by fasting and are often fatal, with the in vivo mechanisms essentially unknown. Since the genes of the rate controlling enzymes of these pathways are tissue and developmentally regulated at the transcriptional level, we measured, throughout neonatal development, the steady-state mRNA levels of long-chain, medium-chain, and short-chain (SCAD) acyl-CoA dehydrogenases, pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), carbamyl phosphate synthetase I (CPS), ornithine transcarbamylase (OTC), and argininosuccinate synthetase (AS) in fed or fasted SCAD-deficient BALB/ByJ mice compared to BALB/cBy controls. Overall, our results showed no major effects on expression of acyl-CoA dehydrogenases due to SCAD deficiency, regardless of age or fasting. In SCAD-deficient mice we found depressed mRNA expression and enzyme activity for the urea cycle enzymes CPS and AS at 6 days of age, and found no apparent effects on expression of gluconeogenic enzymes PC or PEPCK. There was a period of overall lower gene expression for most genes at 6 and 15 days, which appears to be in parallel with the developmental period when children with these diseases are most severely affected.
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PMID:Effects of short-chain acyl-CoA dehydrogenase deficiency on development expression of metabolic enzyme genes in the mouse. 873 88

The effect of anisoosmolarity on the abundance of various mRNA species was examined in perfused rat liver and H4IIE rat hepatoma cells. Hyperosmotic exposure (385 mosmol/l) of isolated rat livers increased mRNA levels for tyrosine aminotransferase (TAT) by 246% and those for phosphoenolpyruvate carboxykinase (PEPCK) by 186%, whereas hypoosmotic exposure (225 mosmol/l) decreased their levels to 43% and 42%, respectively. mRNA levels for fructose-1,6-bisphosphatase (FBP), argininosuccinate lyase (ASL), argininosuccinate synthetase (ASS), glutamine synthetase (GS), glutaminase (GA) and glucokinase (GK) were largely unaffected. In H4IIE cells the modulation of TAT and PEPCK mRNA levels by anisoosmotic exposure was similar to that found in perfused rat liver. ASL and glutaminase mRNA levels were influenced in an opposite manner. The effects of anisoosmolarity on PEPCK mRNA levels in H4IIE cells were largely abolished in the presence of the protein kinase inhibitors H-7, H-89 and HA-1004. Other protein kinase inhibitors such as Go-6850, KN-62, Rp-8-CPT-cAMPS, rapamycin, wortmannin, genistein or herbimycin did not prevent the osmosensitivity of PEPCK mRNA levels. Also pertussis and cholera toxin, vanadate and colchicine did not affect the osmosensitivity of PEPCK mRNA levels. The data suggest that anisoosmotic exposure acts on the levels of some but not all mRNA species and that this action may involve changes in protein phosphorylation. They further indicate that the recently identified osmosensitive signal transduction pathway which involves a G-protein and tyrosine kinase dependent activation of mitogen-activated protein kinases is apparently not involved in the osmoregulation of PEPCK mRNA levels.
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PMID:Anisoosmotic regulation of hepatic gene expression. 892 14

In order to test the possibility that free fatty acids are the mediator of the abnormal expression of urea cycle enzyme genes in carnitine-deficient juvenile visceral steatosis (JVS) mice, the effects of fatty acids on urea cycle enzyme, carbamoylphosphate synthetase (CPS) and argininosuccinate synthetase (ASS), mRNA levels were examined in rat primary cultured hepatocytes. Addition of a synthetic glucocorticoid hormone, dexamethasone, caused increases in CPS and ASS mRNAs. Further addition of oleic acid suppressed the induction of CPS and ASS mRNAs by dexamethasone. In contrast, the phosphoenolpyruvate carboxykinase (PEPCK) mRNA level induced by dexamethasone was enhanced in the presence of oleic acid. The effects were reversed on further addition of carnitine. The mRNA levels of these enzymes induced by dibutyryl cAMP were not affected by the addition of oleic acid. A study of the specificity of fatty acids revealed that long-chain fatty acids of more than 16 carbons chain length had a suppressive effect on the CPS mRNA level induced by dexamethasone and that the presence of double bonds enhanced the effect. The changes in gene expression of CPS, ASS and PEPCK caused by the fatty acids in the cultured hepatocytes were very similar to those observed in the liver of JVS mice. The AP-1 DNA binding activity in the presence of dexamethasone was slightly enhanced by the addition of oleic acid. These results suggest that the long-chain fatty acids not metabolized in JVS mice are mediators of the abnormal gene expression in the liver which results in hyperammonemia.
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PMID:Long-chain fatty acids suppress the induction of urea cycle enzyme genes by glucocorticoid action. 898 69


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