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Pyruvate carboxylase

pyruvate carboxylase
This gene encodes pyruvate carboxylase, which requires biotin and ATP to catalyse the carboxylation of pyruvate to oxaloacetate. The active enzyme is a homotetramer arranged in a tetrahedron which is located exclusively in the mitochondrial matrix. Pyruvate carboxylase is involved in gluconeogenesis, lipogenesis, insulin secretion and synthesis of the neurotransmitter glutamate. Mutations in this gene have been associated with pyruvate carboxylase deficiency. Alternatively spliced transcript variants with different 5' UTRs, but encoding the same protein, have been found for this gene. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: ACID, V1a, CAN, Insulin, HAD
Papers on pyruvate carboxylase
Metabolic engineering of CHO cells to alter lactate metabolism during fed-batch cultures.
New
Durocher et al., Montréal, Canada. In J Biotechnol, Feb 2016
Recombinant yeast pyruvate carboxylase (PYC2) expression was previously shown to be an effective metabolic engineering strategy for reducing lactate formation in a number of relevant mammalian cell lines, but, in the case of CHO cells, did not consistently lead to significant improvement in terms of cell growth, product titer and energy metabolism efficiency.
Leptin regulates energy metabolism in MCF-7 breast cancer cells.
New
Roca et al., Palma, Spain. In Int J Biochem Cell Biol, Feb 2016
Analysis of pyruvate dehydrogenase (PDH), lactate dehydrogenase (LDH) and pyruvate carboxylase (PC) together with the pentose-phosphate pathway enzyme glucose-6 phoshate dehydrogenase (G6PDH) revealed that leptin favors the use of glucose for biosynthesis.
The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux.
Review
New
Shulman et al., In J Clin Invest, Feb 2016
Macrophage-induced WAT lipolysis also stimulates hepatic gluconeogenesis, promoting fasting and postprandial hyperglycemia through increased fatty acid delivery to the liver, which results in increased hepatic acetyl-CoA content, a potent activator of pyruvate carboxylase, and increased glycerol conversion to glucose.
Short communication: Regulation of hepatic gluconeogenic enzymes by dietary glycerol in transition dairy cows.
New
Donkin et al., West Lafayette, United States. In J Dairy Sci, Jan 2016
The objective of this study was to examine the effect of glycerol on expression of pyruvate carboxylase (PC), cytosolic and mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-C and PEPCK-M), and glucose-6-phosphatase.
Integrated, Step-Wise, Mass-Isotopomeric Flux Analysis of the TCA Cycle.
New
Impact
Kibbey et al., New Haven, United States. In Cell Metab, Dec 2015
Comprehensive steady-state and dynamic analyses of key metabolic rates (pyruvate dehydrogenase, β-oxidation, pyruvate carboxylase, isocitrate dehydrogenase, and PEP/pyruvate cycling) were calculated from the position-specific transfer of (13)C from sequential precursors to their products.
Pyruvate carboxylation enables growth of SDH-deficient cells by supporting aspartate biosynthesis.
New
Impact
Gottlieb et al., Padova, Italy. In Nat Cell Biol, Oct 2015
By identifying pyruvate carboxylase as essential for the proliferation and tumorigenic capacity of SDH-deficient cells, this study revealed a metabolic vulnerability for potential future treatment of SDH-associated malignancies.
Effect of Roux-en-Y gastric bypass-induced weight loss on the transcriptomic profiling of subcutaneous adipose tissue.
New
García-Fuentes et al., Astana, Kazakhstan. In Surg Obes Relat Dis, Aug 2015
RESULTS: Microarray analysis revealed that the overexpressed differentially expressed genes have a prominent role in the pathways involved in biosynthetic processes, especially lipid or carboxylic ones (stearoyl-Coenzyme A desaturase-1, fatty acid desaturase-1, fatty acid elongase-6, ATP citrate lyase, fatty acid synthase, lipin-1, monoacylglycerol O-acyltransferase, patatin-like phospholipase domain containing-3, phosphate cytidylyltransferase-2, cholesteryl ester transfer protein, transmembrane 7 superfamily member 2, pyruvate carboxylase, and glycogen synthase 2).
A jack of all trades: the multiple roles of the unique essential second messenger cyclic di-AMP.
Review
New
Stülke et al., Göttingen, Germany. In Mol Microbiol, Jul 2015
Moreover, in Listeria monocytogenes c-di-AMP controls the activity of pyruvate carboxylase, an enzyme that is required to replenish the citric acid cycle.
Hepatic acetyl CoA links adipose tissue inflammation to hepatic insulin resistance and type 2 diabetes.
New
Impact
Shulman et al., New Haven, United States. In Cell, Mar 2015
Using a novel in vivo metabolomics approach, we show that the major mechanism by which insulin suppresses HGP is through reductions in hepatic acetyl CoA by suppression of lipolysis in white adipose tissue (WAT) leading to reductions in pyruvate carboxylase flux.
Rapid and robust generation of long-term self-renewing human neural stem cells with the ability to generate mature astroglia.
Schwamborn et al., Münster, Germany. In Sci Rep, 2014
The hNSC-derived astrocytes showed high activity of pyruvate carboxylase as assessed by stable isotope assisted metabolic profiling.
The cyclic dinucleotide c-di-AMP is an allosteric regulator of metabolic enzyme function.
Impact
Woodward et al., Seattle, United States. In Cell, 2014
Using a chemical proteomics screen for c-di-AMP-interacting proteins in the pathogen Listeria monocytogenes, we identified several broadly conserved protein receptors, including the central metabolic enzyme pyruvate carboxylase (LmPC).
Leptin reverses diabetes by suppression of the hypothalamic-pituitary-adrenal axis.
Impact
Shulman et al., New Haven, United States. In Nat Med, 2014
We show that the higher rates of hepatic gluconeogenesis in all these models could be attributed to hypoleptinemia-induced activity of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in higher rates of adipocyte lipolysis, hepatic conversion of glycerol to glucose through a substrate push mechanism and conversion of pyruvate to glucose through greater hepatic acetyl-CoA allosteric activation of pyruvate carboxylase flux.
Discovery of small molecule probe that shows anti-tubercular activity via Mtb bioA (DAPA synthase) enzyme inhibition
Review
Palmer et al., Bethesda, United States. In Unknown Journal, 2014
Biotin (vitamin H) is the cofactor responsible for activation of carbon dioxide in acyl-CoA carboxylases involved in fatty acid metabolism and pyruvate carboxylase in gluconeogenesis.
Nearly 50 years in the making: defining the catalytic mechanism of the multifunctional enzyme, pyruvate carboxylase.
Review
Zeczycki et al., Greenville, United States. In Febs J, 2014
Numerous steady-state kinetic studies have examined the complex catalytic reaction mechanism of the multifunctional enzyme, pyruvate carboxylase (PC).
Ammonia metabolism and hyperammonemic disorders.
Review
Walker, Southampton, United Kingdom. In Adv Clin Chem, 2013
Deficiencies of urea cycle enzymes, citrin, and pyruvate carboxylase demonstrate the roles of isolated pathways in ammonia metabolism.
Pyruvate carboxylase is expressed in human skeletal muscle.
GeneRIF
Gaster et al., Odense, Denmark. In Biochem Biophys Res Commun, 2010
PC protein is easily detectable by streptavidin blot and the presence of considerable amounts of PC in cultured human myotubes and in human muscle tissue was shown.
Decreased levels of metabolic enzymes in pancreatic islets of patients with type 2 diabetes.
GeneRIF
Ostenson et al., Madison, United States. In Diabetologia, 2009
The activities of pyruvate carboxylase (PC) were decreased by 65% in pancreatic islets of patients with type 2 diabetes.
Structural insights on pathogenic effects of novel mutations causing pyruvate carboxylase deficiency.
GeneRIF
Bonnefont et al., Paris, France. In Hum Mutat, 2009
Nine novel mutations of the PC gene, in five unrelated patients, are reported.
The molecular basis of pyruvate carboxylase deficiency: mosaicism correlates with prolonged survival.
GeneRIF
De Vivo et al., New York City, United States. In Mol Genet Metab, 2008
Eight novel mutations were identified in PC from 8 pyruvate carboxylase deficiency patients.
Crystal structures of human and Staphylococcus aureus pyruvate carboxylase and molecular insights into the carboxyltransfer reaction.
GeneRIF
Tong et al., New York City, United States. In Nat Struct Mol Biol, 2008
The crystal structures at 2.8-A resolution of full-length PC from Staphylococcus aureus and the C-terminal region (missing only the BC domain) of human PC, is reported.
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