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Query: EC:4.1.1.49 (phosphoenolpyruvate carboxykinase)
 4,654 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The functional significance of gluconeogenesis in prolonging endurance during submaximal activity was assessed in untrained and endurance-trained rats. Gluconeogenesis was inhibited at the phosphoenolpyruvate carboxykinase reaction by 3-mercaptopicolinic acid (3-MPA). Endurance was significantly reduced by 3-MPA in untrained (-32%; P less than 0.005) and in trained rats (-26%; P less than 0.001). Metabolic correlates of fatigue were examined in trained rats. At exhaustion, 3-MPA-treated rats had only 3% of resting hepatic glycogen, 46% of resting white quadriceps glycogen, and 37% of resting blood glucose. All of these substrates were at higher levels in sham-injected controls after the same duration of running (130 min). Glycogen levels in red quadriceps, blood lactate levels, and blood glycerol levels were not different between groups. Plasma free fatty acid levels were elevated to the same extent in both groups after 90 min of activity, remained high at 130 min in controls, but had returned to resting levels in the severely hypoglycemic 3-MPA-treated rats at exhaustion. The results indicate that gluconeogenesis is important for maintaining blood glucose levels and for prolonging endurance time during submaximal activity.
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PMID:Reduced running endurance in gluconeogenesis-inhibited rats. 372 4

The metabolism of glycerate and aspartate was investigated in perfused rat kidneys. The major pathway active for aspartate metabolism and NH3 production was found to include transamination, and not the purine nucleotide cycle. Pyruvate cycling was identified as a means by which reducing potential is generated in the cytosol for glucose and lactate production from these substrates. Inhibition of mitochondrial pyruvate transport caused an inhibition of glucose production, accumulation of lactate and pyruvate in the perfusate, and a decrease in the [lactate]/[pyruvate] ratio in kidneys perfused with aspartate. These data indicate a role of mitochondrial pyruvate transport in the provision of cytosolic reducing potential. With either aspartate or glycerate, 3-mercaptopicolinic acid (3-MPA) suppressed glucose synthesis and caused accumulation of malate plus fumarate within the kidney. Glucose production from glycerate was much less sensitive to the presence of 3-MPA than was glucose production from aspartate, illustrating a phosphoenolpyruvate carboxykinase (PEPCK)-independent pathway for the cycling of pyruvate. In aspartate-perfused kidneys, the presence of 3-MPA, at concentrations that completely blocked glucose accumulation in the perfusate, did not affect the rate of NH3 production and had only a minor effect on the rate of aspartate uptake. These data allow for an estimation of the rate of pyruvate formation from aspartate of about 1 mumol/min per kidney under conditions of complete PEPCK inhibition. Thus a PEPCK-independent pathway is operative for amino acid oxidation and pyruvate formation in perfused kidneys. The NADP-linked, but not the NAD-linked, 'malic' enzyme activity of the kidney cortex was found to be sufficient to catalyse this estimated rate of pyruvate formation.
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PMID:The involvement of pyruvate cycling in the metabolism of aspartate and glycerate by the perfused rat kidney. 380 Sep 11

3-Mercaptopicolinic acid (3-MPA) is reportedly a specific inhibitor of phosphoenolpyruvate (PEP) carboxykinase and has hitherto been used accordingly to elucidate the metabolic role of PEP carboxykinase in vitro and in vivo. We show that 3-MPA has multiple effects on intermediary metabolism in hemidiaphragms from 40 h-starved rats. It decreases the release of lactate + pyruvate and alanine in hemidiaphragms provided with no added substrate or with valine, leucine or isoleucine. Moreover, irrespective of the substrate provided (none, valine, leucine, isoleucine, glucose, acetate, oleate), 3-MPA decreases the [lactate]/[pyruvate] ratio. 3-MPA is without effect on 14CO2 production from [U-14C]valine, [1-14C]valine, [1-14C]leucine, [U-14C]isoleucine or [1-14C]oleate, but stimulates 14CO2 production from [U-14C]glucose and [1-14C]pyruvate and inhibits 14CO2 production from [1-14C]acetate. Glycolytic flux (measured as 3H2O formation from [5-3H]glucose) is stimulated by 3-MPA. It is concluded that 3-MPA has site(s) of actions other than PEP carboxykinase and that the putative role of PEP carboxykinase in alanine synthesis de novo in skeletal muscle from tricarboxylic acid-cycle intermediates and related amino acids requires reappraisal.
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PMID:The role of phosphoenolpyruvate carboxykinase in muscle alanine synthesis. 615 38

3-Mercaptopicolinate (3-MPA) is a specific inhibitor of phosphoenolpyruvate carboxykinase (PEP CK). In vivo the hypoglycaemic action of 3-MPA in 24 h-starved rats was abolished on intragastric glucose refeeding. Nonetheless, 3-MPA decreased hepatic glycogen content and rate of synthesis in starved animals re-fed glucose. The inference is that on re-feeding after starvation hepatic glycogen is synthesised mainly de novo via glyconeogenesis involving PEP CK. 3-MPA increased hepatic lipogenesis in water- and glucose-fed normal and diabetic rats. This increase is presumed to result from inhibition of PEP CK and consequent diversion of pyruvate from gluconeogenesis to lipogenesis. In contrast, 3-MPA inhibited brown-fat lipogenesis in water- and glucose-fed rats.
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PMID:Direction of carbon flux in starvation and after refeeding: in vitro and in vivo effects of 3-mercaptopicolinate. 667 46

The role of PEPCK in the stimulation of NH3 production by acute acidosis was examined by perfusing isolated rat kidneys in the presence of the PEPCK inhibitor, MPA (0.15 mM). The response of kidneys perfused with physiologic quantities of glutamine to both acute respiratory (increase in pCO2) and metabolic acidosis (decrease in bicarbonate concentration) was assessed. Although MPA decreased renal NH3 production at pH 7.4, it had no effect on the stimulation of ammoniagenesis produced by either acute respiratory or acute metabolic acidosis. Thus the stimulation of NH3 production by an acute decline in pH must result from an effect on a metabolic step prior to the conversion of oxaloacetate to phosphoenolpyruvate.
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PMID:Influence of phosphoenolpyruvate carboxykinase inhibition on the response of NH3 production to acute acidosis. 686 69

3-Mercaptopicolinic acid (3-MPA), an inhibitor of phosphoenolpyruvate carboxykinase, was employed to study the role of organic acid decarboxylation during C(4) photosynthesis. Treatment of detached Panicum maximum leaves with 5 mm 3-MPA inhibited photosynthesis 70 to 75%. Oxygen was found to have no effect on the degree of inhibition. The postillumination (14)CO(2) burst associated with P. maximum photosynthesis was almost abolished by 5 mm 3-MPA. The turnover rates of malate and aspartate during C(4) photosynthesis were severely reduced as well as the rates of formation of C(3) cycle intermediates in P. maximum leaves treated with 3-MPA. These results are interpreted as direct evidence for the fixation of CO(2), arising from the decarboxylation of oxaloacetate, by the C(3) cycle in bundle sheath cells of P. maximum leaves.
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PMID:Oxaloacetate as the Source of Carbon Dioxide for Photosynthesis in Bundle Sheath Cells of the C(4) Species Panicum maximum. 1666 57

There is evidence that the CO(2)-concentrating mechanism in the marine diatom Thalassiosira weissflogii operates as a type of single-cell C(4) photosynthesis. In quantitative-PCR assays, we observed 2- to 4-fold up-regulation of two phosphoenolpyruvate carboxylase (PEPC) gene transcripts in Thalassiosira pseudonana cells adapted to low pCO(2), but did not detect such regulation in Phaeodactylum tricornutum grown under similar conditions. Transcripts encoding phosphoenolpyruvate carboxykinase did not appear to be regulated by pCO(2) in either diatom. In T. pseudonana and T. weissflogii, net CO(2) fixation was blocked by 3,3-dichloro-2-(dihydroxyphosphinoyl-methyl)-propenoate (a specific inhibitor of PEPC), but was restored by about 50% and 80%, respectively, by addition of millimolar concentrations of KHCO(3). In T. pseudonana, T. weissflogii, and P. tricornutum, rates of net O(2) evolution were reduced by an average of 67%, 55%, and 62%, respectively, in the presence of 20 microm quercetin, also an inhibitor of PEPC. Quercetin promoted net CO(2) leakage from inhibited cells to levels in excess of the equilibrium CO(2) concentration, suggesting that a fraction of the HCO(3)(-) taken up is fated to leak back into the medium as CO(2) when PEPC activity is blocked. In parallel to these experiments, in vitro assays on crude extracts of T. pseudonana demonstrated mean inhibition of 65% of PEPC activity by quercetin. In the presence of 5 mm 3-mercaptopicolinic acid (3-MPA), a classic inhibitor of phosphoenolpyruvate carboxykinase, photosynthetic O(2) evolution was reduced by 90% in T. pseudonana. In T. weissflogii and P. tricornutum, 5 mm 3-MPA totally inhibited net CO(2) fixation and O(2) evolution. Neither quercetin nor 3-MPA had a significant inhibitory effect on photosynthetic O(2) evolution or CO(2) uptake in the marine chlorophyte isolates Chlamydomonas sp. or Dunaliella tertiolecta. Our evidence supports the idea that C(4)-based CO(2)-concentrating mechanisms are generally distributed in diatoms. This conclusion is discussed within the context of the evolutionary success of diatoms.
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PMID:Expression and inhibition of the carboxylating and decarboxylating enzymes in the photosynthetic C4 pathway of marine diatoms. 1799 42