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)

A primary rabbit kidney epithelial cell culture system has been developed which retains differentiated functions of the renal proximal tubule. In addition, the cells have a distinctive metabolism and spectrum of hormone responses. The primary cells were observed to retain in vitro a Na+-dependent sugar transport system (distinctive of the proximal segment of the nephron) and a Na+-dependent phosphate transport system. Both of these transport processes are localized on the apical membrane of proximal tubule cells in vivo. In addition, probenicid-sensitive p-aminohippurate (PAH) uptake was observed in basolateral membranes of the primary tubule cells, and the PAH uptake by these vesicles occurred at a rate that was very similar to that observed with membranes derived from the original tissue. Several other characteristics of the primary cells were examined, including hormone-sensitive cyclic AMP production and phosphoenolpyruvate carboxykinase (PEPCK) activity. Like the cells in vivo, the primary proximal tubule cells were observed to produce significant cyclic AMP in response to parathyroid hormone, but not in response to arginine vasopressin or salmon calcitonin. Significant PEPCK activity was observed in the particulate fraction derived from a homogenate of primary rabbit kidney proximal tubule cells.
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PMID:Primary rabbit kidney proximal tubule cell cultures maintain differentiated functions when cultured in a hormonally defined serum-free medium. 255 82

In the presence of 0.5 mM extracellular Ca2+ concentration both 1-34 human parathyroid hormone fragment (0.5 micrograms/ml) as well as 0.1 mM dibutyryl cAMP stimulated gluconeogenesis from lactate in renal tubules isolated from fed rabbits. However, these two compounds did not affect glucose synthesis from pyruvate as substrate. When 2.5 mM Ca2+ was present the stimulatory effect of the hormone fragment on gluconeogenesis from lactate was not detected but dibutyryl cAMP increased markedly the rate of glucose formation from lactate, dihydroxyacetone and glutamate, and inhibited this process from pyruvate and malate. Moreover, dibutyryl cAMP was ineffective in the presence of either 2-oxoglutarate or fructose as substrate. Similar changes in glucose formation were caused by 0.1 mM cAMP. As concluded from the 'crossover' plot the stimulatory effect of dibutyryl cAMP on glucose formation from lactate may result from an acceleration of pyruvate carboxylation due to an increase of intramitochondrial acetyl-CoA, while an inhibition by this compound of gluconeogenesis from pyruvate is likely due to an elevation of mitochondrial NADH/NAD+ ratio, resulting in a decrease of generation of oxaloacetate, the substrate of phosphoenolpyruvate carboxykinase. Dibutyryl cAMP decreased the conversion of fracture 1,6-bisphosphate to fructose 6-phosphate in the presence of both substrates which may be secondary to an inhibition of fructose 1,6-bisphosphatase.
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PMID:Substrate-dependent effect of 1-34 human parathyroid hormone fragment, dibutyryl cAMP and cAMP on gluconeogenesis in rabbit renal tubules. 287 69

In chickens, the kidney possesses a distinct cytosolic phosphoenolpyruvate carboxykinase activity which is not found in the liver. This activity is subject to long-term regulation by diet and changes in acid-base status. The activity is increased during starvation or metabolic acidosis. In addition, an unidentified component of some standard chicken diets results in altered activity. Using a specific cDNA probe the abundance of PEPCK mRNA has been determined in chicken kidney in vivo and in vitro. The abundance of PEPCK mRNA in chicken kidney increases during starvation and is rapidly decreased after refeeding carbohydrate. In isolated kidney tubules the abundance of the mRNA is increased after incubation with glucocorticoids, dibutyryl cAMP or hormones acting via changes in the concentration of cAMP (parathyroid hormone, epinephrine). Phorbol esters or hormones acting via calcium-dependent mechanisms were without effect. The results support the hypothesis that in the chicken the kidney is the major site of gluconeogenesis from substrates other than lactate and thus plays an important role in the maintenance of glucose homeostasis.
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PMID:Hormonal and nutritional regulation of phosphoenolpyruvate carboxykinase mRNA levels in chicken kidney. 291 3

By using a glucose microassay and the technique for isolated renal-tubule perfusion in vitro, the addition of 3-mercaptopicolinate, a gluconeogenesis inhibitor which inhibits phosphoenolpyruvate carboxykinase specifically, was found to abolish the effects of parathyroid hormone on gluconeogenesis and phosphate-transport rate in isolated rabbit renal proximal straight tubules, suggesting that these parathyroid-hormone actions may share some unknown, yet 3-mercaptopicolinate-inhibitable, intracellular processes.
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PMID:The inhibition of parathyroid-hormone actions on gluconeogenesis and phosphate transport by 3-mercaptopicolinate in rabbit renal proximal tubules. 395 29

The effects of intravenous salmon calcitonin on tissue carbohydrate and redox metabolism were studied in rat kidney in situ and were compared to the effects of EGTA infusion. Calcitonin (0.8 MRC U, in bous) caused, after 10-20 min, a reductive shift of the cytosolic NAD redox pair, and an oxidative shift of the mitochondrial NAD redox pair. It also caused a stimulation of glycolysis with the cross-over between phosphoenolpyruvate and pyruvate. These results were reproduced by treatments of hypocalcemia with EGTA or with thyroparathyroidectomy. Most of the effects were opposite in direction to the reported effects of CaCl2 and parathyroid hormone. The above results suggest that in kidney calcitonin causes a stimulation of pyruvate kinase, and/or inhibition of phosphoenolpyruvate carboxykinase, and that the effects are related to changes in the intracellular calcium.
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PMID:Involvement of calcium in calcitonin induced stimulation of glycolysis in rat kidney in situ. 681 8

In vivo, bicarbonate can affect proximal tubule intermediary metabolism, including gluconeogenesis, ammoniagenesis and maintenance of the mitochondrial substrate supply. In vitro, rabbit proximal tubule cells (RPTC) in primary culture revert from gluconeogenesis to glycolysis and their mitochondrial metabolism remains lower than in vivo. To determine whether the bicarbonate buffer system could have an effect on these deregulations, RPTC in primary culture grown in the absence of insulin and glucose in the culture medium were developed either with the standard sodium bicarbonate buffer with 5% CO2 or with a Hepes hydrogen ion buffer in the presence of 0.5% CO2. Duration of the bicarbonate-free cultures was increased until at least day 17 after seeding, compared with day 11 in bicarbonate-buffered cultures. As could be expected, succinate dehydrogenase activity remained stable as a function of time in bicarbonate-free cultures while an early marked decrease of this activity occurred from seeding in cultures developed in the presence of bicarbonate buffer. Compared to bicarbonate-buffered cells, higher phosphoenolpyruvate carboxykinase activity concomitant with lower intracellular lactate dehydrogenase activity was observed in cultures developed in the absence of bicarbonate, which is indicative of closer carbohydrate metabolism orientation to the in vivo situation for RPTC. Immunofluorescence staining of RPTC with monoclonal antibodies directed to neutral endopeptidase (NEP), and dipeptidyl-peptidase IV (DPP II) showed similar extensive labelling with DPP and NEP in both culture conditions. Confocal microscopy analysis of NEP subcellular distribution, showed exclusive targetting of NEP to the apical plasma membranes. In both models, cAMP production was stimulated by parathyroid hormone and unaffected by arginine vasopressin. In conclusion, bicarbonate withdrawal from the culture medium (without changing the pH of the medium) allows a marked improvement of mitochondrial capacity and carbohydrate metabolism pattern without any loss of differentiated properties.
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PMID:Effects of the medium HCO3-/CO2 buffer system on differentiation and intermediary metabolism properties of rabbit proximal tubule cells in primary culture. 897 88

The major component of urinary acid excretion is NH4+. To be appropriately excreted in urine, NH4+ must be synthesized by proximal tubular cells, secreted into the proximal tubular fluid, reabsorbed by the medullary thick ascending limb (MTAL) to be accumulated in the medullary interstitium, and finally secreted in medullary collecting ducts. Each step of this renal pathway is highly regulated and, in addition to acute events mediated by peptide hormones such as parathyroid hormone, the control of gene expression explains how the renal handling of NH4+ fully adapts to chronic changes in the acid-base status. Several targets have been identified at the gene expression level to account for the adaptation of renal NH4+ synthesis and transport in response to an acid load. These are the key enzymes of ammoniagenesis (mitochondrial glutaminase and glutamate dehydrogenase) and gluconeogenesis (phosphoenolpyruvate carboxykinase) in the proximal tubule, the apical Na(+)-K+(NH4+)-2Cl- cotransporter of the MTAL, and the basolateral Na(+)-K+(NH4+)-2Cl- cotransporter of medullary collecting ducts. At least two factors control the expression of these genes during metabolic acidosis: an acid pH and glucocorticoids, which appear to act in concert to coordinate the adaptation of various tubular cell types. The present review focuses on some aspects of these regulations that have been recently elucidated.
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PMID:Renal handling of NH4+ in relation to the control of acid-base balance by the kidney. 1202 11