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.

Metabolic differentiation of rabbit skeletal muscle as induced by specific innervation.

Abstract: Cross-innervations and re-innervations were performed on the slow (“red”) m. soleus and the fast (“white”) m. extensor digitorum of the rabbit. Innervation of the slow soleus muscle with “fast” motor neurons causes a significant change of the metabolic type of the muscle. This transformation consists in a parallel increase of the activity levels of glycogen phosphorylase, of all the investigated glycolytic enzymes (phosphofructokinase, triosephosphate isomerase, triosephosphate dehydrogenase, phosphoglycerate kinase, glycerate phosphomutase, phosphopyruvate hydratase, lactate dehydrogenase), of adenylate kinase and mitochondrial glycerolphosphate dehydrogenase. A concomitant and parallel decrease is found in the activity levels of extramitochondrial hexokinase, and alanine aminotransferase, of all the investigated enzymes of the citric acid cycle (intramitochondrial citrate synthase, and succinate dehydrogenase, extra- and intramitochondrial malate dehydrogenase, and NADP isocitrate dehydrogenase), of intramitochondrial 3-hydroxyacyl-CoA dehydrogenase and glutamate dehydrogenase, and of extra- and intramitrochondrial aspartate aminotransferase. In spite of the marked changes in absolute activities, no alterations occur with regard to the ratios of enzymes and enzyme groups which by comparison of functionally different muscles have been classified as constant. Changes in the activity ratios concern the same enzymes which in previous studies have been shown to be characteristic of the metabolic type (phosphorylase/hexokinase, triosephosphate dehydrogenase/citrate synthase, lactate dehydrogenase/citrate synthase, triosephosphate dehydrogenase/3-hydroxyacyl-CoA dehydrogenase, adenylate kinase/creatine kinase). The alterations show that a conversion of the metabolic type from “slow” to “fast” takes place and indicate a specific influence of the innervation on metabolic differentiation in muscle, that is the control of a specific pattern of enzyme synthesis. Due to the obvious failure of innervation of the fast extensor muscle with “slow” motor neurons from the tibial nerve, no significant changes were observed in this muscle.

Gene-protein relationships of the alpha-keto acid dehydrogenase complexes of Escherichia coli K12: isolation and characterization of lipoamide dehydrogenase mutants.

Abstract: SUMMARY: Ten independent lipoamide dehydrogenase mutants (lpd) of Escherichia coli were isolated by selecting strains which required supplements of acetate plus succinate for best growth on glucose. They would not grow on unsupplemented medium (except anaerobically) nor would they grow with single supplements of acetate or lipoate, but they responded slowly to lysine plus methionine or succinate. Bacteria-free extracts of the mutants had between 1 and 10% of parental lipoamide dehydrogenase activity and no activity for the pyruvate and α-ketoglutarate dehydrogenase complexes could be detected. Evidence that the mutants contained the dehydrogenase (E1) and transacylase (E2) components of the complexes and were deficient only in the lipoamide dehydrogenase (E3) components was obtained from studies with mixtures containing lpd mutant extracts and either extracts of other mutants having defined lesions or purified lipoamide dehydrogenases, e.g. overall pyruvate dehydrogenase complex could be reconstituted with extracts of aceE and F mutants and the α-ketoglutarate complex was similarly reconstituted with sucA and B extracts. Furthermore, both complexes could be restored by adding extract of an aceE, sucA double-amber mutant (which lacks both types of E1 and E2 component but has 30% of parental lipoamide dehydrogenase activity) or with purified bacterial and mammalian lipoamide dehydrogenases. The bacterial enzymes were several times more efficient than the mammalian enzyme for restoring pyruvate dehydrogenase complex activity. Genetic studies indicated that the wild-type phenotype could be restored by single reversion or transduction events and they confirmed that the mutants are deficient only in lipoamide dehydrogenase. The mutant phenotype was introduced into a recipient strain by cotransduction with leu +. This indicates that there is a lipoamide dehydrogenase gene in the leu region of the Escherichia coli linkage map and strongly supports the view that the E3 components of both α-ketoacid dehydrogenase complexes are specified by a single lipoamide dehydrogenase gene (lpd).

Regulation of lactose fermentation in group N streptococci.

Abstract: Group N streptococci, which have the lactose phosphoenolpyruvate (PEP)-dependent phosphotransferase system (PTS) and phospho-β-d-galactosidase (β-Pgal), grew rapidly on lactose and converted more than 90% of the sugar to l-lactate. In contrast, Streptococcus lactis 7962, which does not have a β-Pgal, grew slowly on lactose and converted only 15% of the sugar to l-lactate. With glucose and galactose, this strain had growth rates and fermentation patterns similar to those of other S. lactis strains, suggesting that the rapid and homolactic fermentation of lactose that is characteristic of group N streptococci is dependent upon a functional PEP-dependent PTS and the presence of β-Pgal. Seventeen strains of group N streptococci were examined for the activator specificities of pyruvate kinase and lactate dehydrogenase. The properties of each enzyme from all the strains, including S. lactis 7962, were similar. Pyruvate kinase had a broad activator specificity, whereas activation of lactate dehydrogenase was specific for ketohexose diphosphate. All intermediates of lactose metabolism from the hexose phosphates to the triose phosphates activated pyruvate kinase. No activation was obtained with adenosine 5′-monophosphate. K+ and Mg2+ were required for pyruvate kinase activity but could be replaced by NH4+ and Mn2+, respectively. Lactate dehydrogenase was activated equally by fructose-1,6-diphosphate and tagatose-1,6-diphosphate, the activation characteristics being pH dependent. The roles of pyruvate kinase and lactate dehydrogenase in the regulation of lactose fermentation by group N streptococci are discussed.

Control of glutamate metabolism. the effect of pyruvate

Abstract: THERE is evidence that under normal conditions glucose is the main substrate utilized by the brain (c j . MCILWAIN, 1959). A possible alternative substrate is glutamate, since the glutamate concentration is relatively high in the brain and it is oxidized at a high rate by brain slices in vitro (WEIL-MALHERBE, 1936). It has been inferred recently, from the specific activity of the respiratory 14C0, produced when brain slices are incubated with labelled metabolites, that glutamate is oxidized in preference to glucose (CHAIN, COHEN and POCCHIARI, 1962; SWAIMAN, MILSTEIN and COHEN, 1963). On the other hand HASLAM and KREBS (19633), who measured the net metabolic changes also, obtained evidence of an inhibition of glutamate oxidation by glucose. There are three main pathways by which glutamate can be oxidized in brain preparations. In mitochondrial systems glutamate is mainly utilized through transamination with oxaloacetate followed by oxidation of a-oxoglutarate in the tricarboxylic acid cycle (KREBS and BELLAMY, 1960; BALAZS and HASLAM, 1965; BALAZS, 1965). This pathway accounts for more than three-quarters of the glutamate utilized and with some preparations the contribution of this route has been found to be more than 90 per cent. The rest of the glutamate removed is probably oxidized mainly through the glutamate dehydrogenase, but some can also be decarboxylated and utilized through the y-aminobutyrate pathway. Since the oxidation of glutamate in viuo normally occurs in the presence of pyruvate derived from the blood glucose, the effect of pyruvate on the utilization of glutamate was investigated. The results agree with the observations of HASLAM and KREBS (19636) with brain homogenates, in that they show an inhibition by pyruvate of glutamate utilization. The mechanism of this effect of pyruvate has now been analysed. I t is suggested that the inhibitory action of pyruvate, and certain characteristic features of the operation of the tricarboxylic acid cycle reported previously, are factors affecting the steady-state concentration of glutamate, aspartate and alanine in the liver and brain in viro (BALLZS and RICHTER, 1962; HASLAM and KREBS, 1963a; BALAZS, MAGYAR and RICHTER, 1964).