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

Two gene loci for the E1 alpha subunit of the pyruvate dehydrogenase (PDH) complex have been mapped in the mouse by in situ hybridization. One locus maps to the X chromosome in the region F3-F4, the other to chromosome 19, in band B close to the centromere. This arrangement is exactly comparable to the situation in man where there is an X-linked PDH E1 alpha locus and an autosomal locus on chromosome 4. Comparison of the regional localization of the human and mouse X-linked PDH E1 alpha genes provides further information concerning sites of rearrangement of segments of the X chromosome during mammalian evolution. The human autosomal PDH E1 alpha gene is a "processed" gene, which lacks the introns that are present in the X-linked gene. It codes for a testis-specific E1 alpha subunit that is only expressed after the onset of spermatogenesis. The comparative mapping results in the mouse suggest that the genetic organization and pattern of expression of the two PDH E1 alpha genes is the same in the two species.
Somat Cell Mol Genet 1990 Sep
PMID:Pyruvate dehydrogenase E1 alpha subunit genes in the mouse: mapping and comparison with human homologs. 212 29

The recovery of both contractile performance and metabolic response of rat heart following 1 h of ischemia after equilibration with glucose + insulin (glucose-ischemia) or with pyruvate (pyruvate-ischemia), was tested in normoxic reperfusion in the presence of glucose + insulin, pyruvate, lactate or acetate. In glucose-ischemia only the reperfusion with pyruvate results in a complete recovery of the contractile force (left ventricular pressure, LVP) (170%) and good recovery of high energy phosphate compounds. Lower LVP and tissue energy charge were found in glucose reperfusion and even less in lactate and acetate reperfusion. Disappearance of the IMP accumulated during ischemia is evident only in the pyruvate reperfusion indicating a higher metabolic recovery. On the contrary in pyruvate-ischemia all types of reperfusion tested were effective in reactivating the contractile force (although acetate to a lesser extent); the contractile activity was accompanied by a good recovery of phosphocreatine, ATP, energy charge and by the decrease of IMP. Large decreases of adenine nucleotides and NADP and lower decreases of NAD are observed during ischemia/reperfusion in both systems. Pyruvate-ischemia is quite similar to, if not worse than glucose-ischemia, for all the metabolic parameters considered, but not worse for the possibility of recovery. Some specific effect of pyruvate should be exerted during the ischemic phase. The mechanism of pyruvate protection is discussed in relationship to: (i) the possible activation of pyruvate dehydrogenase, (ii) the activation of NADPH-dependent peroxide scavenging systems, (iii) the direct scavenging action of pyruvate on H2O2.
J Mol Cell Cardiol 1990 Feb
PMID:The protective action of pyruvate on recovery of ischemic rat heart: comparison with other oxidizable substrates. 218 87

The overexpression of a subgene encoding a hybrid lipoyl domain of the dihydrolipoamide acetyltransferase component of the pyruvate dehydrogenase complex of Escherichia coli has previously been shown to result in the formation of lipoylated and unlipoylated products. Overexpression of the same subgene in a lipoic acid biosynthesis mutant growing under lipoate-deficient conditions has now been shown to produce domains modified by octanoylation as well as unmodified domains. It was concluded from the mass of a lipoyl-binding-site peptide that the modification involves N6-octanoylation of the lysine residue (Lys244) that is normally lipoylated, and this was confirmed by the trypsin-insensitivity of the corresponding Lys244-Ala-245 bond, and the absence of modification in a mutant domain in which Lys244 is replaced by Gln. This novel protein modification raises interesting questions concerning the pathway of lipoic acid biosynthesis and the mechanism of enzyme lipoylation.
Mol Microbiol 1990 Jun
PMID:Octanoylation of the lipoyl domains of the pyruvate dehydrogenase complex in a lipoyl-deficient strain of Escherichia coli. 221 17

The upstream activation site of the pyruvate decarboxylase gene, PDC1, of Saccharomyces cerevisiae contains an RPG box, and mediates the increase in expression of a PDC1-lacZ fusion gene during growth on glucose. Oligonucleotide replacement experiments indicate that the RPG box functions as an absolute activator of expression, but other elements (possibly CTTCC repeats) are required for carbon source regulation, and maximal expression. Gel retardation and oligonucleotide competition experiments suggest that the DNA binding factor TUF interacts with the RPG box in the upstream region of PDC1. Binding of TUF factor is not carbon source dependent in in vitro experiments, and is probably not responsible for glucose induction of PDC1 expression.
Mol Gen Genet 1990 Sep
PMID:TUF factor binds to the upstream region of the pyruvate decarboxylase structural gene (PDC1) of Saccharomyces cerevisiae. 227 85

Neonatal and adult rat islets, cultured for 7-9 days in the presence of 10.5 mM D-glucose, were incubated for 120 min with either D-glucose (2.8 and 16.7 mM) or L-leucine (1.0 and 20.0 mM). The total and anaerobic rates of glycolysis, as judged respectively through the generation of 3H2O from D-[5-3H]glucose and 14C-labelled lactate from D-[3,4-14C]glucose or D-[6-14C]glucose were higher in neonatal than adult islets, but increased to a lesser relative extent in neonatal than adult islets in response to a rise in hexose concentration. The flow through the pentose phosphate pathway, as judged from the difference between D-[1-14C]glucose and D-[6-14C]glucose oxidation was higher in neonatal than adult islets. The flow through the reaction catalyzed by pyruvate dehydrogenase, as judged from the oxidation of D-[3,4-14C]glucose, was lower in neonatal than adult islets incubated in the presence of 16.7 mM (but not 2.8 mM) D-glucose. The oxidation of acetyl residues relative to their generation rate, as judged from the ratio of D-[6-14C]glucose to D-[3,4-14C]glucose oxidation, was not affected by the hexose concentration whether in neonatal or adult islets, but was about twice higher in the latter than former islets. The rate of D-[6-14C]glucose oxidation was also higher in adult than neonatal islets, especially at the high concentration of D-glucose. In both neonatal and adult islets, a rise in hexose concentration stimulated preferentially the oxidation of D[3,4-14C]glucose or D-[6-14C]glucose relative to the utilization of D-[5-3H]glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1990 Oct 01
PMID:D-glucose and L-leucine metabolism in neonatal and adult cultured rat pancreatic islets. 229 40

The ability of polyamines and other cationic compounds including monoamines, amino acids, poly-L-arginine, poly-D-lysine and poly-L-lysine, to alter pyruvate dehydrogenase (PDH) activity in mitochondria from rat epididymal adipocytes was determined. PDH was assayed with the substrate [1-14C] pyruvate in the presence of 0.05 mM Ca2+ and Mg2+. Nine of the fourteen compounds tested at 0.1 mM caused a significant increase (procaine, 3-(beta-morpholinopropionyl) benzo [b]thiophene [VII], spermine, spermidine, putrescine, lysine and tryptophan) or decrease (poly-L-arginine, 3-(beta-piperidinopropionyl) benzo[b]thiophene) in PDH activity. None of these compounds nonenzymatically decarboxylated [1-14C] pyruvate to release 14CO2. NaF, a PDH phosphatase inhibitor, suppressed the stimulatory effects of those compounds tested: procaine, tryptophan, VII, spermine and spermidine. These results imply that these five compounds activate PDH activity through stimulation of the PDH phosphatase. When the Mg2+ concentration was increased from 0.05 to 4.5 mM, the stimulatory effect of spermine was increased, consistent with the finding by others that spermine lowers the Km of the enzyme for Mg2+. However, at Mg2+ concentrations greater than 0.3 mM, the stimulatory effect of VII was unaltered, procaine failed to alter PDH activity, lysine inhibited PDH activity, and poly-L-lysine stimulated PDH activity. Therefore, polyamines and other positively charged small molecules may be physiologic regulators of PDH activity.
Mol Cell Biochem 1990 Mar 27
PMID:The effect of amino acids, monoamines and polyamines on pyruvate dehydrogenase activity in mitochondria from rat adipocytes. 234 44

We have studied the effects of insulin on several aspects of cell metabolism in the insulin-sensitive, nonfusing muscle cell line BC3H-1. In the absence of exogenous hexose, insulin did not alter basal glycogen synthase percentage I activity, or attenuate the increase in intracellular cAMP content, the activation of glycogen phosphorylase a, or the decrease in glycogen synthase I brought about by beta-adrenergic receptor activation with epinephrine. In contrast, both insulin and the tumor-promoting phorbol ester, tetradecanoylyl phorbol acetate markedly increased mitochondrial pyruvate dehydrogenase activity in the absence of hexose. Both glycogen synthase phosphatase and glycogen synthase kinase activities were present in BC3H-1 cell extracts and were regulated in the expected manner by glucose 6-phosphate and cAMP, respectively. Since the pattern of partial insulin resistance seen in BC3H-1 myocytes would require that several potentially insulin-sensitive enzymes be insensitive to insulin-generated signals, the most likely explanation for these data is that the myocytes are defective in some mechanism of insulin signaling which is independent of the mechanism for pyruvate dehydrogenase activation.
Mol Pharmacol 1986 Dec
PMID:Hexose-independent activation of glycogen synthase and pyruvate dehydrogenase by insulin is dissociated in the mouse BC3H-1 cell line. 243 Dec 65

Poly(A)+ RNA was isolated from Ascaris suum body wall muscle and translated in a cell-free rabbit reticulocyte lysate system. Specific antisera and immunoglobulins against the alpha-pyruvate dehydrogenase and dihydrolipoyl transacetylase components of ascarid pyruvate dehydrogenase complex were used to immunoprecipitate individual radiolabelled polypeptides from the in vitro translation mixtures. Both polypeptides appeared to be synthesized as preproteins about 1.5 and 8 kDa larger than the corresponding native proteins. Incubation of the dihydrolipoyl transacetylase preprotein with an ascarid high-speed mitochondrial supernatant fraction resulted in the formation of a polypeptide with apparent molecular weight intermediate in size between the preprotein and the native enzyme. This processing was insensitive to phenylmethylsulfonyl fluoride and leupeptin but was completely abolished by EDTA. These results suggest that in A.suum, as in other organisms, mitochondrial matrix proteins coded by the nuclear genome are synthesized as larger preproteins and processed by a specific, metal-dependent mitochondrial matrix protease.
Mol Biochem Parasitol 1988 May
PMID:In vitro synthesis and processing of components of the Ascaris suum pyruvate dehydrogenase complex. 245 26

In vitro deletion and site-directed mutagenesis of the aceF gene of Escherichia coli was used to generate dihydrolipoamide acetyltransferase (E2p) polypeptide chains containing various permutations and combinations of functional and non-functional lipoyl domains. A lipoyl domain was rendered non-functional by converting the lipoylatable lysine residue to glutamine. Two- and three-lipoyl domain E2p chains, with lipoyl-lysine (Lys244) substituted by glutamine in the innermost lipoyl domains (designated +/- and +/+/-, respectively), and similar chains with lipoyl-lysine (Lys143) substituted by glutamine in the outer lipoyl domains (designated -/+ and -/-/+), were constructed. In all instances, pyruvate dehydrogenase complexes were assembled in vivo around E2p cores composed of the modified peptide chains. All the complexes were essentially fully active in catalysis, although the complex containing the -/-/+ version of the E2p polypeptide chain showed a 50% reduction in specific catalytic activity. Similarly, active-site coupling in the complexes containing the +/-, +/+/- and -/+ constructions of the E2p chains was not significantly different from that achieved by the wild-type complex. However, active-site coupling in the complex containing the -/-/+ version of the E2p chain was slightly impaired, consistent with the reduced overall complex activity. These results indicate that during oxidative decarboxylation there is no mandatory order of reductive acetylation of repeated lipoyl domains within E2p polypeptide chains, and strongly suggest that the three tandemly repeated lipoyl domains in the wild-type E2p chain function independently in the pyruvate dehydrogenase complex.
J Mol Biol 1989 Aug 20
PMID:Reductive acetylation of tandemly repeated lipoyl domains in the pyruvate dehydrogenase multienzyme complex of Escherichia coli is random order. 250 11

A cDNA was identified using an oligonucleotide designed by comparing the sequences of bacterial and yeast pyruvate decarboxylase. The sequence of the cDNA identified by the oligonucleotide contained an open reading frame that encoded a protein of 65 kDa that was similar in sequence to bacterial and yeast pyruvate decarboxylase. This protein was selectively precipitated by an antiserum specific for maize PDC. Northern-blot analysis shows that PDC mRNA is anaerobically induced. Southern-blot analysis of maize genomic DNA indicated that the maize PDC gene has a single or low copy number.
Plant Mol Biol 1989 Aug
PMID:Maize pyruvate decarboxylase mRNA is induced anaerobically. 251 13


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