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)

In different metabolic states renal phosphoenolpyruvate carboxykinase (PEP-CK) activities are closely correlated with in vitro glucogenic rates, suggesting a limitation of the glucogenic capacity of kidney by this enzyme. Stimulation of renal gluconeogenesis from pyruvate, lactate, and succinate by lysine and glutamine was therefore associated with a regulatory attack of these amino acids at the level of PEP-carboxykinase. This postulate was confirmed by the failure of lysine to stimulate glucose synthesis from fructose. Experimental support for an interference of glutamine and PEP-carboxykinase was obtained by a study on the inactivation of this enzyme in kidney cortex homogenates: A rapid inactivation of enzyme activity within 40-50 min could be slowed down by glutamine. In addition the inactivation was counteracted by ATP. At suboptimal concentrations of the trinucleotide its effect was potentiated by c-AMP and c-GMP. Studies on the effect of ATP on PEP-carboxykinase in kidney cortex homogenates from rats in different metabolic states revealed: In homogenates from carbohydrate fed animals extreme low activities of PEP-CK were not altered by ATP, whereas elevated enzyme activities after a protein rich diet could be further raised by a factor of 2 or 3 by ATP. GTP and ITP could substitute for ATP. An extension of these studies on hepatic enzymes showed a similar inactivation of tyrosine aminotransferase (TAT) and a protective effect of ATP. The data obtained from these experiments favour an interconversion of PEP-carboxykinase and tyrosine aminotransferase into different forms as possible mechanism for their regulation.
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PMID:Regulation of phosphoenolpyruvate carboxykinase by glutamine and ATP as possible control mechanisms of renal gluconeogenesis. 18 82

Ammoniagenesis and gluconeogenesis have been studied in foetal rat kidneys during the five last days of gestation by measuring in vitro NH3 and glucose productions from glutamine and by assaying activities of soluble phosphoenolpyruvate carboxykinase(PEPCK) and glucose 6-phosphatase (G6Pase). These studies were carried out in normal (mean blood pH: 7.30) and acidotic (pH: 7.12) foetuses. In normal foetuses, NH3 production by kidney cortex slices remains constant throughout the studied period of development, at a level 10-fold lower than the maternal one. On day 20 of gestation, a low glucose production (20-fold lower than the maternal one) appears for the first time. This may be related to an increase of PEPCK and G6Pase activities which occurs between day 19 and 20. In 20 days old foetuses, NH4Cl induced acidosis stimulates NH3 production but has no effect on PEPCK activity and glucose production. A response of gluconeogenesis to acidosis is observed one day later (day 21).
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PMID:Development of ammonia and glucose productions from glutamine in foetal rat kidney; effects of metabolic acidosis. 21 16

The effects of starvation on the acid-base status of the rat and on the glucoeogenic and ammoniagenic capacity of rat renal-cortical slices were examined. Starvation for 48 or 72 hr did not affect acid-base status, and urinary ammonia production did not change. Kidney cortical slices from starved as compared to fed rats showed increased gluconeogenic capacity when incubated with the substrated pyruvate, succinate, fumarate, malate, 2-oxyoglutarate, glutamine and glutamate. Renal cortical tissue from starved rats also had increased activity of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase. Renal cortical slices from starved rats did not differ from those from fed rats in the ability to produce ammonia from glutamine or glutamate, nor was there any difference inhe activity of glutaminase between these groups. These results show that renal gluconeogenic capacity is increased in starved rats in the absence of systemic acidosis, and starvation does not lead to an increase in urinary ammonia excretion or renal ammoniagenic capacity.
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PMID:Effect of starvation on renal metabolism in the rat. 24 54

In kidney-cortex slices from rats fed on 2.0 mg of ochratoxin A/kg per day for 2 days, gluconeogenesis from pyruvate is decreased by 26%, and renal phosphoenolpyruvate carboxykinase activity is lowered by about 55%. Gluconeogenesis from 10 mM-lactate or 20 mM-malate or -glutamine is also significantly decreased. Hepatic phosphoenolpyruvate carboxykinase is unchanged or increased, and hexokinase activity in kidney and liver remains unaffected. We conclude that ochratoxin A in vivo is an inhibitor of renal phosphoenolpyruvate carboxykinase activity, which is responsible, at least in part, for the block in renal gluconeogenesis.
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PMID:Inhibition of renal gluconeogenesis in rats by ochratoxin. 48 43

The purpose of this study was to investigate factors which may regulate ammoniagenesis in the kidney cortex. Emphasis was placed on the segment of the pathway by which the carbons derived from glutamine must exit from the mitochondrion. These pathways were compared in the rat with high rates of ammoniagenesis and the rabbit which has a low rate of ammoniagenesis. The dicarboxylate transporter, which is essential for ammoniagenesis, has a maximum velocity which was much lower in the rabbit. The malate concentration required for half-maximal rates of transport was 14 nmol/mg mitochondrial protein and similar in both species. There was no effect of chronic metabolic acidosis on dicarboxylate transporter activity. The tricarboxylate transporter activity with phosphoenol pyruvate as substrate also had a low activity in the rabbit kidney-cortex mitochondria. The maximum velocity of phosphate dependent glutaminase, glutamate dehydrogenase and phosphoenolpyruvate carboxykinase were all much greater than the maximal rate of ammoniagenesis observed in vivo in the rabbit. Therefore, the low rates of ammoniagenesis and the failure to adapt to acidosis in the rabbit are best explained by factors influencing the dicarboxylate transporter.
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PMID:Role of the mitochondrial anion transporters in the regulation of ammoniagenesis in renal cortex mitochondria of the rabbit and rat. 49 11

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

The influence of protein intake on acid excretion and renal glutamine metabolism was investigated and compared to the effects of NH4Cl-induced metabolic acidosis. Rats fed a diet containing 55% casein excreted more ammonia, phosphate, sulphate, and chloride than did rats fed a 13% casein diet, but, when they were given an 0.1 M NaHCO3 solution to drink, ammonia excretion was no longer elevated. Renal phosphate-dependent glutaminase and phosphoenolpyruvate carboxykinase activities, ammoniagenesis by isolated mitochondria, and the rate of renal gluconeogenesis were all elevated in the rats fed the high-protein diet but not if these rats also drank the sodium bicarbonate solution. Increased glutaminase and phosphoenolpyruvate carboxykinase activities, mitochondrial ammoniagenesis, and gluconeogenesis were all evident in rats made acidotic with NH4Cl. It is concluded that these metabolic adaptations evident in the kidneys of rats fed the high-protein diet are due to the acidogenic effects of increased protein intake.
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PMID:Renal glutamine metabolism in rats fed high-protein diets. 69 20

Experiments were carried out on rats to evaluate the possible regulatory roles of renal glutaminase activity, mitochondrial permeability to glutamine, phosphoenolpyruvate carboxykinase activity and systemic acid-base changes in the control of renal ammonia (NH(3) plus NH(4) (+)) production. Acidosis was induced by drinking NH(4)Cl solution ad libitum. A pronounced metabolic acidosis without respiratory compensation [pH=7.25; HCO(3) (-)=16.9mequiv./litre; pCO(2)=40.7mmHg (5.41kPa)] was evident for the first 2 days, but thereafter acid-base status returned towards normal. This improvement in acid-base status was accompanied by the attainment of maximal rates of ammonia excretion (onset phase) after about 2 days. A steady rate of ammonia excretion was then maintained (plateau phase) until the rats were supplied with tap water in place of the NH(4)Cl solution, whereupon pCO(2) and HCO(3) (-) became elevated [55.4mmHg (7.37kPa) and 35.5mequiv./litre] and renal ammonia excretion returned to control values within 1 day (recovery phase). Renal arteriovenous differences for glutamine always paralleled rates of ammonia excretion. Phosphate-dependent glutaminase and phosphoenolpyruvate carboxykinase activities and the rate of glutamine metabolism (NH(3) production and O(2) consumption) by isolated kidney mitochondria all increased during the onset phase. The increases in glutaminase and in mitochondrial metabolism continued into the plateau phase, whereas the increase in the carboxykinase reached a plateau at the same time as did ammonia excretion. During the recovery phase a rapid decrease in carboxykinase activity accompanied the decrease in ammonia excretion, whereas glutaminase and mitochondrial glutamine metabolism in vitro remained elevated. The metabolism of glutamine by kidney-cortex slices (ammonia, glutamate and glucose production) paralleled the metabolism of glutamine in vivo during recovery, i.e. it returned to control values. The results indicate that the adaptations in mitochondrial glutamine metabolism must be regulated by extra-mitochondrial factors, since glutamine metabolism in vivo and in slices returns to control values during recovery, whereas the mitochondrial metabolism of glutamine remains elevated.
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PMID:Glutamine metabolism in the kidney during induction of, and recovery from, metabolic acidosis in the rat. 70 90

1. Glucose production from L-lactate was completely inhibited 24h after carbon tetrachloride treatment in liver from 48h-starved rats. The activities of phosphoenolpyruvate carboxykinase, fructose diphosphatase and glucose 6-phosphatase were decreased by this treatment in fed and starved rats, whereas lactate dehydrogenase activity was only decreased in fed animals. 2. The production of glucose by renal cortical slices from fed rats previously treated with carbon tetrachloride was enhanced when L-lactate, pyruvate and glutamine but not fructose were used as glucose precursors. Renal phosphoenolpyruvate carboxykinase activity was increased in this condition. 3. This increase was counteracted by cycloheximide or actinomycin D, suggesting that the effect was due to the synthesis de novo of the enzyme. 4. The pattern of hepatic gluconeogenic metabolites in treated animals was characterized by an increase in lactate, pyruvate, malate and citrate as well as a decrease in glucose 6-phosphate, suggesting an impairment of liver gluconeogenesis in vivo. 5. In contrast, the profile of renal metabolites suggested that gluconeogenesis was operative in the treated rats, as indicated by the marked increase in the content of phosphoenolpyruvate, 2-phosphoglycerate, 3-phosphoglycerate and glucose 6-phosphate. 6. It is postulated that renal gluconeogenesis could contribute to the maintenance of glycaemia in carbon tetrachloride-treated rats.
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PMID:Induction of rat kidney gluconeogenesis during acute liver intoxication by carbon tetrachloride. 70 98

1. Neither alloxan-diabetes nor starvation affected the rate of glucose production in hepatocytes incubated with lactate, pyruvate, propionate or fructose as substrates. In contrast, glucose synthesis with either alanine or glutamine was increased nearly 3- and 12-fold respectively, in comparison with that in fed rabbits. 2. The addition of amino-oxyacetate resulted in about a 50% decrease in glucose formation from lactate in hepatocytes isolated from fed, alloxan-diabetic and starved rats, suggesting that both mitochondrial and cytosolic forms of rabbit phosphoenolpyruvate carboxykinase function actively during gluconeogenesis. 3. Alloxan-diabetes resulted in about 2-3-fold stimulation of urea production from either amino acid studied or NH4Cl as NH3 donor, whereas starvation caused a significant increase in the rate of ureogenesis only in the presence of alanine as the source of NH3. 4. As concluded from changes in the [3-hydroxybutyrate]/[acetoacetate] ratio, in hepatocytes from diabetic animals the mitochondrial redox state was shifted toward oxidation in comparison with that observed in liver cells isolated from fed rabbits.
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PMID:Effect of alloxan-diabetes on gluconeogenesis and ureogenesis in isolated rabbit liver cells. 74 58


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