Disease relevance of Pc

• In contrast, pyruvate carboxylase from two bacterial species, Pseudomonas citronellolis and Axotobacter vinelandii, appears to be a dimer with a molecular weight (2.5 X 10(5)) about half that of the animal and yeast species [1].
• In the human hepatoma, as in the rat hepatoma, the activities of PC, PEPCK, and G6Pase were considerably reduced, compared to those in the host liver [2].
• In rat pancreatic islets and insulinoma cells, only transcripts D and E, generated from the distal promoter of the PC gene, were expressed [3].
• Although reductions in mGPD and PC may contribute to the abnormal insulin secretion present in overt diabetes, they are modest compared with the severe reductions seen in inherited inborn errors of metabolism [4].
• This analog will not activate Escherichia coli phosphoenolpyruvate carboxylase or rat liver pyruvate carboxylase, two enzymes which require acetyl-CoA as an obligate activator [5].

Psychiatry related information on Pc

• We suggest that the reductions in brain dopamine concentrations are a consequence of ortho-substituted PCB congener-induced inhibition of the synthesis of dopamine during critical periods of development acting, perhaps, in concert with PCB-induced changes in cholinergic receptor function [6].
• Postnatal reflexes, motor activity and male reproductive performance were evaluated in rat offspring after exposure to PCB 118 [7].
• Maximal electroshock seizure tests on postweaning rats showed that perinatal PCB exposure decreased seizure severity of both the 2.5 and 26 ppm groups as indicated by increased durations of forelimb and hindlimb flexion and decreased duration of hindlimb extension [8].

High impact information on Pc

• A 5-fluorodeoxyuridine-substituted oligonucleotide cDNA detects rat liver pyruvate carboxylase mRNA on a RNA gel blot with a dissociation temperature only 10 degrees C below the measured melting temperature in solution [9].
• Varieties of pyruvate carboxylase [pyruvate: CO2 ligase (ADP-forming), EC 6.4.1.1] obtained from the livers of several species of vertebrates, including humans, all show the same basic structure [1].
• In the case of pyruvate carboxylase from chicken liver each polypeptide chain contains a biotin moiety, thus supporting the thesis that the tetramer contains four identical polypeptide chains [1].
• The change in the rate of gluconeogenesis was not accompanied by changes in any of the following parameters: phosphoenolpyruvate carboxykinase or pyruvate carboxylase activities or mitochondrial ATP/ADP or cytosolic NADH/NAD+ ratios [10].
• Mammalian pyruvate carboxylase: effect of biotin on the synthesis and translocation of apo-enzyme into 3T3-L adipocyte mitochondria [11].

Chemical compound and disease context of Pc

• Glucose increased PC transcripts from the distal promoter when the insulinoma cells were maintained in 10 mM glucose [3].
• Given the cerebellar symptomatology of biotin-dependent diseases and other lactic acidoses, we hypothesized that cerebellar pyruvate carboxylase activity might be differentially low or especially sensitive to cofactor deprivation [12].
• Effect of streptozotocin-induced diabetes mellitus on the turnover of rat liver pyruvate carboxylase and pyruvate dehydrogenase [13].
• Salmonella tester strains TA98, TA100 and TA1535 and liver microsomal preparations (S9) from rats induced with PB or Aroclor 1254 (PCB) were employed [14].
• Toxicity of hydroxylated and quinoid PCB metabolites: inhibition of gap junctional intercellular communication and activation of aryl hydrocarbon and estrogen receptors in hepatic and mammary cells [15].

Biological context of Pc

• beta-Cell adaptation to insulin resistance. Increased pyruvate carboxylase and malate-pyruvate shuttle activity in islets of nondiabetic Zucker fatty rats [16].
• The sequence of rat PC cDNA contains an open reading frame of 3537 nucleotides encoding a polypeptide of 1178 amino acids with a calculated M(r) of 129848 [17].
• On the basis of partial proteolysis and sequence homology with PC from other organisms (yeast, mosquito, mouse and human) and with other biotin enzymes, three functional domains, namely the biotin carboxylation domain, the transcarboxylation domain and the biotinyl domain, have been identified [17].
• A composite 3945-bp cDNA that encodes rat pyruvate carboxylase (PC) has been constructed from clones isolated from a rat liver cell cDNA library and the nucleotide sequence has been determined [18].
• A rapid purification method for rat liver pyruvate carboxylase and amino acid sequence analyses of NH2-terminal and biotin peptide [19].

Anatomical context of Pc

• Northern analysis revealed that PC mRNA is highly expressed in rat liver, kidney, adipose tissue and brain, moderately expressed in heart, adrenal gland and lactating mammary gland, and expressed at a low level in spleen and skeletal muscle [17].
• However, a greater diversion of pyruvate metabolism through the pyruvate-malate shuttle is suggested by unchanged pyruvate carboxylase Vmax and a fourfold higher release of malate from isolated mitochondria [20].
• We conclude that the decreased mGPD and pyruvate carboxylase in the pancreatic islet of the GK rat result from the diabetic syndrome [21].
• Immunochemical techniques have been utilized to study the effect of thyroid status on the content and rates of synthesis and degradation of pyruvate carboxylase and pyruvate dehydrogenase in rat liver [22].
• It is concluded that insulin increases the flux through pyruvate carboxylase in adipose tissue in part by increasing the transport of pyruvate through the inner mitochondrial membrane [23].

Associations of Pc with chemical compounds

• Thus, our results suggest that PC and the pyruvate shuttles are increased in ZF islets, and this accounts for glucose mitochondrial metabolism being increased when pyruvate dehydrogenase activity is reduced [16].
• Inhibition of PC by 5 mm phenylacetic acid markedly lowered glucose-induced insulin secretion in ZF and ZL islets [16].
• Non-invasive intratracheal inoculation of cryopreserved parasites into Pc- and virus-free rats immunosuppressed by weekly injections of methylprednisolone are key features of the model that result in the development of consistent heavy Pc infections and very few secondary infections by bacteria and fungi [24].
• Equations to calculate the relative rates of pyruvate carboxylase (y), and the equilibration of oxaloacetate with fumarate from the isotopomer distribution are derived [25].
• In summary, a simple model is presented to examine carbon flux from lactate via the pyruvate carboxylase and tricarboxylic acid pathways during gluconeogenesis [26].

Regulatory relationships of Pc

• The specific activity of pyruvate carboxylase in non-parenchymal cells expressed as the percentage of that in parenchymal cells was onlu 2% for glutamate dehydrogenase 4.3% and for cytochrome c oxidase 79.4% [27].

Other interactions of Pc

• Accumulation of 5-8 nmol of Ca2+/mg, which increased the matrix [Ca2+] to 2-5 microM in both preparations, significantly enhanced pyruvate carboxylase flux by 20-30% in the mitochondria from glucagon-treated rats, but had little effect in control preparations [28].
• This fitting yielded rates which we express relative to that of pyruvate carboxylase: citric acid cycle represented by the irreversible alpha-ketoglutarate dehydrogenase = 0.32; citrate synthase = 0.64; reversal of isocitrate dehydrogenase = 0.52; citrate lyase = 0.33, aspartate shuttle = 0.24, and malate shuttle = 0.44 [29].
• About 24 h was required for maximal (de)induction of pyruvate dehydrogenase E1 alpha and pyruvate carboxylase mRNAs, and the amounts of transcripts were proportional to the concentrations of glucose between 1 and 20 mM.(ABSTRACT TRUNCATED AT 400 WORDS)[30]
• The methods previously used to determine PC/PDH in brain were re-evaluated as regards their capacity to discriminate between astrocytic (via pyruvate carboxylase) and neuronal (via malic enzyme) pyruvate carboxylation [31].
• Interference by pyruvate carboxylase in the measurement of acetyl-CoA carboxylase in crude liver preparations [32].

Analytical, diagnostic and therapeutic context of Pc

• Protein components unambiguously identified by peptide mapping are citrate synthase, aconitase, and pyruvate carboxylase [33].
• In addition, rats were pretreated with Aroclor 1254 (PCB), 3-methylcholanthrene (MC), phenobarbital (PB), PhIP and corn oil prior to a single dose of [14C]PhIP, and compared with a control group receiving [14C]PhIP only [34].
• Rat liver pyruvate carboxylase. Purification, detection and quantification of apo and holo forms by immuno-blotting and by an enzyme-linked immunosorbent assay [35].
• These polyspecific antibodies recognize pyruvate carboxylase enzymes alone without cross reactivity with other carboxylases as detected by immunoblotting [36].
• Subsequently, in rats fed the basal diet (30% casein diet) or the diet containing 200 ppm PCB, the specific activities of ascorbic acid in urine and in various tissues were measured 6 hours, 12 hours and 24 hours after the oral administration of L-(l-14C)ascorbic acid [37].

References