Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:6.4.1.1 (pyruvate carboxylase)
1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to profile mRNA expression of argininosuccinate synthetase (AS) and ornithine transcarbamylase (OTC), two enzymes that participate in the formation of urea in liver and compare these with changes in mRNA for pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK) during the periparturient period in dairy cows. Forty-eight multiparous Holstein cows were fed isoenergetic prepartum diets that contained 10% RDP and either 4.0% RUP or 6.2% RUP and either 0, 6, or 12 g/d of rumen-protected choline (RPC) as CapShure (Balchem Corp., Slate Hill, NY). After calving cows received a common diet and continued RPC as per their prepartum assignments. Liver biopsies were obtained on d -28, -14, 1, 28, and 56 relative to calving, and the abundances of AS, OTC, PC, PEPCK, and 18S mRNA were determined by Northern blot analysis of total RNA. The abundance of OTC mRNA was lowest at calving and was decreased by RPC and 6.2% RUP feeding. Feeding 6.2% RUP did not alter AS, PC, or PEPCK mRNA. The expression of AS mRNA increased and PEPCK mRNA tended to increase from calving to 56 DIM. Pyruvate carboxylase mRNA increased more than twofold at calving. The data indicated adaptation to lactation for gluconeogenic enzymes that is not matched in direction and magnitude by changes in mRNA for urea cycle enzymes. Feeding additional protein, as RUP, failed to induce mRNA for key enzymes in gluconeogenesis or ureagenesis.
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PMID:Rumen undegradable protein, rumen-protected choline and mRNA expression for enzymes in gluconeogenesis and ureagenesis in periparturient dairy cows. 1123 34

High-fat (HF) and high-sucrose (SU) diets increase gluconeogenesis. The present study was designed to determine the contributions of pyruvate dehydrogenase, pyruvate carboxylase, phosphoenolpyruvate carboxykinase (PEPCK), and pyruvate kinase fluxes to this accelerated gluconeogenesis (GNEO) in the absence and presence of fatty acids. Male Sprague-Dawley rats were fed an HF, SU, or starch (ST) diet for 1 wk, and hepatocytes or mitochondria were isolated. In the absence of palmitate, the tracer estimated rates of GNEO (nmol. min(-1). mg(-1)) were elevated in hepatocytes isolated from SU (32.3 +/- 1.8) and HF (35.4 +/- 1.8) vs. ST (22.8 +/- 1.5). Pyruvate carboxylase and PEPCK flux rates (nmol. min(-1). mg(-1)) were increased in the SU (47.5 +/- 2.2 and 34.8 +/- 1.5) and HF (49.4 +/- 1.8 and 38.2 +/- 1.8) groups compared with the ST group (32.8 +/- 3.2 and 44.3 +/- 2.0). Palmitate (250-1,000 microM) stimulation of these fluxes was not significantly different among groups. Bromopalmitate, an inhibitor of fat oxidation, abolished differences in GNEO, pyruvate carboxylase, and PEPCK fluxes in HF and SU vs. ST. In isolated mitochondria, pyruvate carboxylation and palmitoyl carnitine oxidation were not significantly different among groups. The results of this study suggest that the increased gluconeogenic flux observed with HF and SU diets is associated with an increased pyruvate flux through pyruvate carboxylase and PEPCK. Moreover, the ability of bromopalmitate to normalize gluconeogenic fluxes suggests that endogenous fatty acids contribute to diet-induced increases in GNEO.
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PMID:Increased pyruvate flux capacities account for diet-induced increases in gluconeogenesis in vitro. 1144 44

The biochemical events associated with the onset of lipid accumulation in Mucor circinelloides and Mortierella alpina, under conditions of nitrogen-limited growth, have been elucidated; they differ in key aspects from those described in oleaginous yeasts. The NAD+:isocitrate dehydrogenases of Mc. circinelloides and Mort. alpina were not absolutely dependent on AMP for activity. Furthermore, changes in the cellular adenine nucleotide pools and energy charge were different from those reported for oleaginous yeasts. In Mc. circinelloides ATP, ADP and AMP concentrations all decreased by 50% after nitrogen limitation, leading to a constant energy charge at the expense of the size of the total adenylate pool. Pyruvate carboxylase in Mc. circinelloides was cytosolic, having implications for the organization of lipid synthesis in filamentous fungi. As a result of the data obtained, a revised and more concerted mechanism for the initiation of storage lipid accumulation is put forward for filamentous fungi.
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PMID:Biochemical events leading to the diversion of carbon into storage lipids in the oleaginous fungi Mucor circinelloides and Mortierella alpina. 1157 64

Long-term exposure of the pancreatic beta cells to free fatty acid (FFA) reportedly inhibits glucose-stimulated insulin secretion. We here studied the impact of FFA on glucose and lipid metabolism in pancreatic beta cells with special reference to insulin secretion. Pancreatic beta-cell line MIN6 was exposed to various concentrations of palmitate for 3 days. Glucose-stimulated insulin secretion and insulin content were decreased corresponding to the concentration of the palmitate exposed. Glycolytic flux and ATP synthesis was unchanged, but pyruvate-stimulated change in NAD(P)H concentration was decreased. Pyruvate carboxylase was decreased at the protein level, which was restored by the removal of palmitate or the inhibition of beta-oxidation. Intracellular content of triglyceride and FFA were elevated, beta-oxidation was increased, and de novo lipogenesis from glucose was decreased. NADPH content and citrate output into the medium, which reflected pyruvate malate shuttle flux, were decreased, but malic enzyme activity was unaffected. The malic enzyme inhibitor alone inhibited insulin response to glucose. In conclusion, long-term exposure of FFA to beta cells inhibits glucose-stimulated insulin secretion via the decreased NADPH contents due to the inhibition of pyruvate carboxylase and malate pyruvate shuttle flux.
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PMID:Metabolic consequence of long-term exposure of pancreatic beta cells to free fatty acid with special reference to glucose insensitivity. 1178 Nov 46

The Rhizobium etli poly-beta-hydroxybutyrate synthase (PhaC) mutant SAM100 grows poorly with pyruvate as the carbon source. The inactivation of aniA, encoding a global carbon flux regulator, in SAM100 restores growth of the resulting double mutant (VEM58) on pyruvate. Pyruvate carboxylase (PYC) activity, pyc gene transcription, and holoenzyme content, which were low in SAM100, were restored in strain VEM58. The genetically engineered overexpression of PYC in SAM100 also allowed its growth on pyruvate. The possible relation between AniA, pyc transcription, and reduced-nucleotide levels is discussed.
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PMID:Effect of aniA (carbon flux regulator) and PhaC (poly-beta-hydroxybutyrate synthase) mutations on pyruvate metabolism in Rhizobium etli. 1191 62

Pyruvate carboxylase (PC) [EC 6.4.1.1] is a biotin-dependent carboxylase that catalyses the conversion of pyruvate to oxaloacetate. Here we have determined the complete nucleotide sequence encoding chicken PC (cPC) by screening a liver cDNA library, by RT-PCR of poly(A)(+) RNA, and by PCR of genomic DNA. The full-length transcript contains an open reading frame of 3537 nucleotides, including the stop codon, encoding a polypeptide of 1178 amino acids with M(r) of 127,262. The amino acid sequence of cPC shows approximately 77% identity to mammalian PC. Limited proteolysis of pure cPC with chymotrypsin yields a major stable 75 kDa C-terminal peptide, including the biotinyl domain and a minor, unstable 39 kDa N-terminal peptide. Northern analysis of poly(A)(+) RNA isolated from chicken liver has shown that cPC's mRNA is approximately 5 kb in length, including a very long 3'-untranslated region.
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PMID:Molecular cloning and domain structure of chicken pyruvate carboxylase. 1215 Sep 61

Pyruvate carboxylase was recently sequenced in Corynebacterium glutamicum and shown to play an important role of anaplerosis in the central carbon metabolism and amino acid synthesis of these bacteria. In this study we investigate the effect of the overexpression of the gene for pyruvate carboxylase (pyc) on the physiology of C. glutamicum ATCC 21253 and ATCC 21799 grown on defined media with two different carbon sources, glucose and lactate. In general, the physiological effects of pyc overexpression in Corynebacteria depend on the genetic background of the particular strain studied and are determined to a large extent by the interplay between pyruvate carboxylase and aspartate kinase activities. If the pyruvate carboxylase activity is not properly matched by the aspartate kinase activity, pyc overexpression results in growth enhancement instead of greater lysine production, despite its central role in anaplerosis and aspartic acid biosynthesis. Aspartate kinase regulation by lysine and threonine, pyruvate carboxylase inhibition by aspartate (shown in this study using permeabilized cells), as well as well-established activation of pyruvate carboxylase by lactate and acetyl coenzyme A are the key factors in determining the effect of pyc overexpression on Corynebacteria physiology.
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PMID:Effect of pyruvate carboxylase overexpression on the physiology of Corynebacterium glutamicum. 1240 33

Pseudomonas aeruginosa ATCC 17933 growing aerobically on ethanol uses a pyrroloquinoline quinone-dependent ethanol oxidation system. A mutant with an interrupted putative mqo gene, in which malate:quinone oxidoreductase (MQO), an enzyme involved in the citric acid cycle/glyoxylate cycle, was defective, showed a severe growth defect on ethanol and was unable to grow on acetate. Glucose, lactate, succinate or malate supported growth of the mutant. However, an NAD-dependent malate dehydrogenase activity could not be detected. Complementation of the mutant by the wild-type allele of the mqo gene restored wild-type behaviour. The wild-type expressed the dye-dependent MQO and NAD(P)-dependent malic enzymes (MEs). Pyruvate carboxylase (PC) was found upon growth of the wild-type and the mutant on all substrates studied. PC activity in the wild-type was induced on glucose and lactate and was always higher on all substrates in the mqo mutant. In P. aeruginosa ATCC 17933, an active MQO is required for growth on ethanol or acetate, while with glucose, lactate, succinate or malate an apparent bypass route operates, with MEs using malate for generating pyruvate, which is carboxylated to oxaloacetate by PC. To the authors' knowledge, this is the first time that a specific mutant MQO phenotype has been observed, caused by the inactivation of a gene encoding MQO activity. mqo of P. aeruginosa ATCC 17933 corresponds to mqoB (PA4640) of the P. aeruginosa PAO1 genome project.
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PMID:Malate:quinone oxidoreductase is essential for growth on ethanol or acetate in Pseudomonas aeruginosa. 1248 Aug 87

L-Lysine has been manufactured using Corynebacterium glutamicum for more than 40 years. Nowadays production exceeds 600,000 tons per year. Based on conventionally bred strains, further improvement of lysine productivity has been achieved by genetic engineering. Pyruvate carboxylase, aspartate kinase, dihydrodipicolinate synthase, homoserine dehydrogenase and the specific lysine exporter were shown to be key enzymes for lysine production and were characterized in detail. Their combined engineering led to a striking increase in lysine formation. Pathway modeling with data emerging from 13C-isotope experiments revealed a coordinated flux through pentose phosphate cycle and tricarboxylic acid cycle and intensive futile cycling between C3 compounds of glycolysis and C4 compounds of tricarboxylic acid cycle. Process economics have been optimized by developing repeated fed-batch techniques and technical continuous fermentations. In addition, on-line metabolic pathway analysis or flow cytometry may help to improve the fermentation performance. Finally, the availability of the Corynebacterium glutamicum genome sequence has a major impact on the improvement of the biotechnological manufacture of lysine. In this context, all genes of the carbon flow from sugar uptake to lysine secretion have been identified and are accessible to manipulation. The whole sequence information gives access to post genome technologies such as transcriptome analysis, investigation of the proteome and the active metabolic network. These multi-parallel working technologies will accelerate the generation of knowledge. For the first time there is a chance of understanding the overall picture of the physiological state of lysine overproduction in a technical environment.
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PMID:Biotechnological manufacture of lysine. 1252 89

To understand the effects of bcl-2 on glucose metabolism and tumor necrosis factor-alpha (TNF-alpha) mediated cytotoxicity, the activities of glycolytic enzymes (hexokinase, 6-phosphofructo-1-kinase, and pyruvate kinase), lactate dehydrogenase, pyruvate carboxylase, and phosphoenolpyruvate carboxykinase were examined with or without TNF-alpha treatment in TNF-alpha sensitive L929 cells and TNF-alpha resistant bcl-2 transfected L929 cells. In TNF-alpha-treated L929 cells, the activities of the glycolytic enzymes and lactate dehydrogenase greatly increased, but there was no detectable change in phosphoenolpyruvate carboxykinase. Pyruvate carboxylase activity decreased by about 25% between 6 and 12 h after TNF-alpha treatment. The activities of the glycolytic enzymes and lactate dehydrogenase in bcl-2 transfected L929 cells were lower than in L929 cells upon TNF-alpha treatment. On the other hand, the activity of pyruvate carboxylase was 20-100% greater after 6 h of TNF-alpha treatment than in the L929 cells. The activity of phosphoenolpyruvate carboxykinase of bcl-2 trasfected L929 cells was lower by up to 25% than in L929 cells after 12 h. The increase of pyruvate carboxylase activity and decrease of phosphoenolpyruvate carboxykinase activity in bcl-2 transfected L929 cells may contribute to the protective effects of bcl-2 against TNF-alpha mediated cytotoxicity.
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PMID:Bcl-2 inhibits tumor necrosis factor-alpha-mediated increase of glycolytic enzyme activities and enhances pyruvate carboxylase activity. 1450 47


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