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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bacillus subtilis SpoIIE is a Ser protein phosphatase whose action on the phosphoprotein SpoIIAA triggers the cell type-specific activation of a sporulation transcription factor. Here we report that SpoIIE displays sequence similarity to the PP2C family of eukaryotic Ser/Thr protein phosphatases, and that residues common to these proteins are required for the function of both SpoIIE and TPD1, a yeast PP2C. These findings suggest that SpoIIE and the PP2C protein phosphatases are structurally related, and reveal a striking formal similarity between the SpoIIAA regulatory circuit and that of mammalian mitochondrial pyruvate dehydrogenase. This similarity may reflect an evolutionarily conserved mechanism of biological regulation based on the interplay of His protein kinase-like Ser kinases and PP2C-like protein phosphatases.
Mol Microbiol 1997 Jan
PMID:Structural relationship between a bacterial developmental protein and eukaryotic PP2C protein phosphatases. 900 20

In a significant number of patients with biochemical evidence of a defect in the E1 (pyruvate dehydrogenase) component of the pyruvate dehydrogenase complex, it has not proved possible to identify a mutation in the gene coding regions. To assess the need for more extensive genetic analysis in these patients and to establish a test system in which to study the biochemical consequences of mutations in the E1alpha subunit gene (which is responsible for the great majority of defined cases of pyruvate dehydrogenase deficiency), we have developed a method to screen for E1alpha gene defects based on complementation of the enzyme deficiency in transformed fibroblast cell lines following transfection and expression of the normal cDNA. Using this system, cell lines from patients with a variety of different defined mutations in the E1alpha gene show restoration of enzyme activity. A number of patients have been identified in whom deficient enzyme activity is not restored by expression of the normal cDNA indicating that an alternative explanation for the enzyme defect must be sought.
Hum Mol Genet 1997 Aug
PMID:Transfection screening for primary defects in the pyruvate dehydrogenase E1alpha subunit gene. 925 85

We have utilized 13C NMR spectroscopy to investigate glucose metabolism in the mouse insulinoma Beta TC3 cell line. Cells were cultured and examined both as monolayers and entrapped in alginate/poly-L-lysine/alginate beads. Entrapped cultures were tested at 3 and 30 days post-entrapment. The purpose of this study was to assess whether the entrapped environment affects glucose metabolism and insulin secretion. Both monolayer and entrapped cultures were fed with 10 mM [1-(13)C]-glucose for 4 hrs. prior to extraction with perchloric acid. Our data revealed that beta TC3 cells possess a reduced tricarboxylic acid (TCA) activity in the entrapment cultures, and that they metabolized pyruvate primarily via pyruvate dehydrogenase regardless of the mode or age of the culture.
Cell Mol Biol (Noisy-le-grand) 1997 Jul
PMID:Towards the development of a bioartificial pancreas: a 13C NMR study on the effects of alginate/poly-L-lysine/alginate entrapment on glucose metabolism by beta TC3 mouse insulinoma cells. 929 94

This study was designed to test the hypothesis that activation of myocardial pyruvate dehydrogenase (PDH) would improve recovery of heart function after brief, severe hemorrhagic shock. Pentobarbital-anesthetized rats were instrumented to monitor arterial blood pressure and right ventricular pressures. Rats were hemorrhaged via femoral artery to 25-30 mmHg mean arterial pressure (MAP) for 60 min, followed by retransfusion of shed blood with either 1.0 cc saline with no dichloroacetate (-DCA) or 1.0 cc saline containing 150 mg/kg sodium dichloroacetate (+DCA). Rats were observed for 3 h after retransfusion. Hearts were freeze-clamped in situ for analysis of adenosine triphosphate (ATP), creatine phosphate (CrP), lactate and pyruvate content as well as PDH activity (PDHa) and total PDH activity (PDHt). Three h after retransfusion, the rate pressure product (RPP=HRxPSP) was 23 000+/-2733 with no DCA treatment v 36 2769 mmHg/min with DCA treatment (P<0.05, ANOVA). Treatment with DCA also increased myocardial tissue content of high energy phosphates (ATP=10.1+/-1.1 and CrP=5.8+/-1.0 micromol/g weight-DCA, v 15.1+/-0.9 and 14.7+/-1.0 micromol/g dry weight+DCA, P<0.05, both measurements). DCA administration also significantly reduced myocardial lactate contents (14.6+/-2.7 micromol/g dry weight-DCA v 5.9+/-1.0+DCA). Hemorrhagic shock did not change PDHa or PDHt compared to hearts obtained during the pre-hemorrhage period. Retransfusion with DCA significantly increased PDHa activity (6.8+/-1.1 micromol/g dry weight/min-DCA v 29.7+/-2.0 micromol/g dry weight/min+DCA). PDHt was not different between controls and DCA-treated groups. These data indicate that activation of myocardial PDH by adding DCA to retransfused blood improved heart function and metabolism after severe hemorrhagic shock.
J Mol Cell Cardiol 1997 Sep
PMID:Activation of pyruvate dehydrogenase improves heart function and metabolism after hemorrhagic shock. 929 69

Alterations in substrate selection and utilisation are characteristics of heart failure of different etiologies and these changes may be involved in the development of contractile dysfunction. Regulation of pyruvate dehydrogenase (PDH) is crucial in determining the relative contribution of glucose oxidation to energy production; however, the role of PDH in the development of heart failure has not been clarified. In this study, we present a reliable and simple method for assaying both the active and total forms of PDH (PDHa and PDHt respectively) in cardiac tissue, and have compared the effects of pressure overload hypertrophy and diabetes on PDH activity. PDHa and PDHt were measured in extracts of hypertrophied hearts after 5 weeks of pressure overload or in hearts after 7 weeks following induction of diabetes. There was no significant change in PDHt in the hypertrophied group, but the fraction of PDH in the active form significantly decreased from 61+/-1% in controls to 36+/-1% (P<0.05). Following diabetes, there was a decrease in the ratio of PDHa:PDHt from 60+/-3% to 11+/-1% (P<0.0001) and PDHt activity -6.2+/-0.9 to 2.7+/-0.4 micromol/min/g wet weight (P<0.02)]. This study reports for the first time that (i) concomitant with the development of compensated hypertrophy, there is a decrease in the fraction of PDH in the active form; and (ii) in the diabetic heart, there is marked decrease in total PDH activity in addition to a decrease in the fraction of PDH in the active form. These results indicate that myocardial substrate delivery to the mitochondria may be impaired in both hypertrophy and diabetes, which may lead to the energy depleted state observed in heart failure.
J Mol Cell Cardiol 1997 Oct
PMID:The effects of hypertrophy and diabetes on cardiac pyruvate dehydrogenase activity. 934 71

Acetaldehyde is one of the intermediate products of ethanolic fermentation, which can be reduced to ethanol by alcohol dehydrogenase (ADH). Alternatively, acetaldehyde can be oxidized to acetate by aldehyde dehydrogenase (ALDH) and subsequently converted to acetyl-CoA by acetyl-CoA synthetase (ACS). To study the expression of ALDHs in plants we isolated and characterized a cDNA coding for a putative mitochondrial ALDH (TobAldh2A) in Nicotiana tabacum. TobALDH2A shows 54-60% identity at the amino acid level with other ALDHs and shows 76% identity with maize Rf2, a gene involved in restoration of male fertility in cms-T maize. TobAldh2A transcripts and protein were present at high levels in the male and female reproductive tissues. Expression in vegetative tissues was much lower and no induction by anaerobic incubation was observed. This suggests that TobALDH expression is not part of the anaerobic response, but may have another function. The use of specific inhibitors of ALDH and the pyruvate dehydrogenase (PDH) complex indicates that ALDH activity is important for pollen tube growth, and thus may have a function in biosynthesis or energy production.
Plant Mol Biol 1997 Oct
PMID:Aldehyde dehydrogenase in tobacco pollen. 934 59

The activity of the beta isoform of protein kinase C (PKC beta) is reduced in the diabetic heart. Since this isozyme has been implicated in insulin action, we tested the hypothesis that PKC beta contributes to the development of impaired glucose metabolism by the noninsulin-dependent diabetic heart. Exposure of the diabetic heart to buffer containing the protein kinase C activator, phorbol myristate acetate, increased PKC beta activity in the membrane. Associated with the improvement in PKC beta activity was a biphasic change in glucose metabolism. The initial phase was characterized by a breakdown in glycogen stores, a stimulation in glucose oxidation and a decrease in endogenous fatty acid oxidation. This was followed by a second phase in which the uptake of glucose was modestly stimulated. Nonetheless, since the phorbol ester did not overcome the diabetes-linked defect in pyruvate dehydrogenase, the increase in glycolytic flux was not associated with a rise in glucose oxidation. Consequently, nearly 50% of the triose units were diverted into lactate and pyruvate production and the generation of ATP from glucose was restricted. Since insulin promotes not only glucose uptake, but also glycogen synthesis and glucose oxidation, the phorbol ester and insulin effects are very different. Thus, the data do not support a role for PKC beta in the development of glucose metabolic defects in the hearts of noninsulin-dependent diabetic rats.
Mol Cell Biochem 1997 Nov
PMID:Is there a link between impaired glucose metabolism and protein kinase C activity in the diabetic heart? 940 65

This study was conducted to determine the time course of metabolic changes associated with a switch from a high-fat to a low-fat diet in rats. Adult rats, maintained on a high-fat diet (42% of energy from fat) for 4-5 weeks were switched to a low-fat diet (11% of energy from fat), and the activities of several liver enzymes were followed. Three different phases could be distinguished. The early phase, complete by 2 days after the switch in diets, included an increase in the activity of glucose 6-phosphate dehydrogenase (pentose phosphate pathway), an increase in pyruvate kinase and pyruvate dehydrogenase activities (terminal end of the glycolytic pathway) and an increase in ATP-citrate lyase and fatty acid synthetase (fatty acid synthesis pathway). The early phase also included a decrease in the activity of phosphoenolpyruvate carboxykinase (PEPCK, gluconeogenesis) and a lower branched-chain amino acid dehydrogenase activity (BCAADH, branched-chain amino acid degradation). The concentration of the allosteric phosphofructokinase regulator, fructose 2,6-bisphosphate (Fru-2,6-P2, glycolysis), decreased during the early phase. An intermediate phase could also be discerned between 3 and 10 days after the switch in diets. In this phase, the decreased Fru-2,6-P2 concentration and the decreased PEPCK and BCAADH activities observed in the early phase were reversed. The late phase occurred 10 days after the dietary switch and was characterized by an increase in the activities of glucokinase (glycolytic pathway) and glycogen phosphorylase (associated with glycogenolysis) and by a decrease in glutamate dehydrogenase, PEPCK and BCAADH activities. These measurements indicate that at least 20 days are required before metabolic changes associated with a switch in diet are complete.
Comp Biochem Physiol B Biochem Mol Biol 1997 Oct
PMID:Time course of enzyme changes after a switch from a high-fat to a low-fat diet. 944 Feb 29

While the presence of a lipoyl-containing protein (protein X) separate from lipoyl transacetylase in the pyruvate dehydrogenase complex (PDC) has been known for some time, until recently only the cDNA for the yeast enzyme has been cloned. We have cloned, sequenced and characterized the cDNA encoding the human protein X and localized the protein X gene to chromosome 11p13. We also report here a new case of protein X deficiency identified immunologically, with decreased activity of PDC and without mutations in the E1alpha subunit or E1beta subunit. We report that the cDNA and gene of this patient for protein X has a homozygous 4 bp deletion, specifically in the putative mitochondrial targeting signal sequence which results in a premature stop codon. This is the first documented case of a molecular defect in pyruvate dehydrogenase protein X.
Hum Mol Genet 1998 Mar
PMID:Detection of a homozygous four base pair deletion in the protein X gene in a case of pyruvate dehydrogenase complex deficiency. 946 10

The mouse X-linked mutants lined and stripey are associated with lethality of affected males in utero and a striping of the coat in carrier females. We demonstrate that the underlying mutations are nested deletions which lie in the Phex-Amelx chromosomal segment conserved between man and mouse. The lined deletion contains less than approximately 0.7 cM of genetic material and includes the growth factor-regulated protein kinase gene, Rsk2. Stripey carries a larger deletion which removes approximately 2.0 cM of genetic material, including Rsk2 and the pyruvate dehydrogenase E1alpha subunit gene, Pdha1 . Since Coffin-Lowry syndrome and neonatal lactic acidosis are associated with mutations in the human homologues of Rsk2 and Pdha1 respectively, lined and stripey provide models for gene deficiencies in these disorders.
Hum Mol Genet 1998 Mar
PMID:Mouse mutants carrying deletions that remove the genes mutated in Coffin-Lowry syndrome and lactic acidosis. 946 16


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