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Pyruvate dehydrogenase kinase

About: Pyruvate dehydrogenase kinase is a research topic. Over the lifetime, 4224 publications have been published within this topic receiving 161052 citations. The topic is also known as: [pyruvate dehydrogenase (lipoamide)] kinase & pyruvate dehydrogenase (lipoamide) kinase.


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Journal ArticleDOI
TL;DR: The simultaneous fermentation of glycerol and sugar by lactobacilli and Lactobacillus buchneri B190 increases both the growth rate and total growth and there is a correlation between the expression of these enzymes and a raised intracellular NAD/NADH ratio.
Abstract: The simultaneous fermentation of glycerol and sugar by lactobacillus brevis B22 and Lactobacillus buchneri B190 increases both the growth rate and total growth. The reduction of glycerol to 1,3-propanediol by the lactobacilli was found to influence the metabolism of the sugar cofermented by channelling some of the intermediate metabolites (e.g., pyruvate) towards NADH-producing (rather than NADH-consuming) reactions. Ultimately, the absolute requirement for NADH to prevent the accumulation of 3-hydroxypropionaldehyde leads to a novel lactate-glycerol cofermentation. As a result, additional ATP can be made not only by (i) converting pyruvate to acetate via acetyl phosphate rather than to the ethanol usually found and (ii) oxidizing part of the intermediate pyruvate to acetate instead of the usual reduction to lactate but also by (iii) reoxidation of accumulated lactate to acetate via pyruvate. The conversion of lactate to pyruvate is probably catalyzed by NAD-independent lactate dehydrogenases that are found only in the cultures oxidizing lactate and producing 1,3-propanediol, suggesting a correlation between the expression of these enzymes and a raised intracellular NAD/NADH ratio. The enzymes metabolizing glycerol (glycerol dehydratase and 1,3-propanediol dehydrogenase) were expressed in concert without necessary induction by added glycerol, although their expression may also be influenced by the intracellular NAD/NADH ratio set by the different carbohydrates fermented.

91 citations

Journal ArticleDOI
TL;DR: Both intramitochondrial complexes are responsible for oxidative decarboxylation of 2-oxobutyrate, but the BCODH is probably the more important complex, particularly in liver, on the basis of kinetic analyses, activity or phosphorylation state of both complexes, competition studies, and the apparent physiological concentration of pyruvate.
Abstract: Purified branched-chain 2-oxo acid dehydrogenase (BCODH) and pyruvate dehydrogenase (PDH) had apparent Km values (microM) for 2-oxobutyrate of 26 and 114, with a relative Vmax. (% of Vmax. for 3-methyl-2-oxobutyrate and pyruvate) of 38 and 45% respectively. The phosphorylation state of both complexes in extracts of mitochondria from rat liver, kidney, heart and skeletal muscle was shown to influence oxidative decarboxylation of 2-oxobutyrate. Inhibitory antibodies to BCODH and an inhibitor of PDH (3-fluoropyruvate) were used with mitochondrial extracts to determine the relative contribution of both complexes to oxidative decarboxylation of 2-oxobutyrate. Calculated rates of 2-oxobutyrate decarboxylation in mitochondrial extracts, based on the kinetic constants given above and the activities of both complexes, were the same as the measured rates. Hydroxyapatite chromatography of extracts of mitochondria from rat liver revealed only two peaks of oxidative decarboxylation of 2-oxobutyrate, with one peak associated with PDH and the other with BCODH. Competition studies with various 2-oxo acids revealed a different inhibition pattern with mitochondrial extracts from liver compared with those from heart or skeletal muscle. We conclude that both intramitochondrial complexes are responsible for oxidative decarboxylation of 2-oxobutyrate. However, the BCODH is probably the more important complex, particularly in liver, on the basis of kinetic analyses, activity or phosphorylation state of both complexes, competition studies, and the apparent physiological concentration of pyruvate, 2-oxobutyrate and the branched-chain 2-oxo acids.

91 citations

Journal ArticleDOI
TL;DR: It is concluded that PEP-synthase plays an important role in the anaplerotic and the biosynthetic reactions which enable the organisms to grow on pyruvate as sole carbon source.
Abstract: Extracts of Escherichia coli are shown to contain an enzyme system which in the presence of Mg 2+ catalyses the direct formation of phospho enol pyruvate from pyruvate and ATP with concomitant formation of AMP and inorganic phosphate. This enzyme, which has been designated 9phospho enol pyruvate synthase9 ( PEP -synthase) has been purified 80-fold and is free of pyruvate kinase activity; PEP synthesis proceeded most rapidly at pH 8 to 8.5. At pH values between 6.2 and 7.5 the enzyme can catalyse the formation of ATP and pyruvate from PEP , AMP and inorganic phosphate; if arsenate is used instead of phosphate, pyruvate and ADP are produced instead. Studies of the enzymic formation of PEP with ATP specifically labelled with 32 P, and of the reverse reaction with [U -14 C] AMP , suggest that the PEP -synthase reaction involves the transfer of a pyrophosphoryl-group. The physiological role of PEP -synthase has been demonstrated with mutants of E. coli devoid of the enzyme: in contrast to wild-type organisms, such mutants neither grow on pyruvate, lactate or alanine, nor form glycogen from lactate. It is thus concluded that PEP -synthase plays an important role in the anaplerotic and the biosynthetic reactions which enable the organisms to grow on pyruvate as sole carbon source.

91 citations

Journal ArticleDOI
TL;DR: MIMOSA measures key metabolic rates from the precursor/product position-specific transfer of (13)C-label between metabolites and has broad applicability to any glucose-oxidizing cell.

91 citations

Journal ArticleDOI
TL;DR: It is shown that overexpression of either PDK1 or LDHA in a rat CNS cell line (B12) confers resistance to Aβ and other neurotoxins, indicating that key Warburg effect enzymes play a central role in mediating neuronal resistance to Αβ or other neurotoxin by decreasing mitochondrial activity and subsequent ROS production.

91 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202329
202234
202161
202063
201959
201851