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

1. The pyruvate dehydrogenase complex from human heart has been partially purified and shown to be regulated by a phosphorylation-dephosphorylation cycle similar to that previously found for other mammalian tissues. 2. Incubation of the complex with ATP (2 mmol/1) led to its inactivation associated with the concomitant incorporation into the protein of 32P from the terminal phosphate group of the ATP. Pyruvate, ADP, thiamin pyrophosphate and dichloroacetate diminished the rate of inactivation by ATP. 3. Pyruvate dehydrogenase phosphatase from human heart requires Mg2+ for activity and is sensitive to Ca2+ at concentrations of a few mumol/1. Similar ionic requirements of the skeletal muscle phosphatase have been demonstrated in a crude tissue extract. 4. The activity of pyruvate dehydrogenase in human adipose tissue was less than 10% of typical values in rats. This could be due to the high level of dietary fat consumed by humans, which is known to repress the enzyme activity in rats.
Clin Sci Mol Med 1976 Nov
PMID:Regulation of the human pyruvate dehydrogenase complex. 18 26

ATP and UTP support microtubule assembly through the action of brain nucleoside-5'-diphosphate kinase on GDP. Penningroth and Kirschner (1977) J. Mol. Biol. 115, 643-673) have proposed that microtubule assembly may occur by either of two mechanisms: indirectly, through nucleoside-5'-diphosphate kinase-catalyzed phosphorylation of uncomplexed GDP and directly by nucleoside-5'-diphosphate kinase-mediated transphosphorylation of tubulin-bound GDP at low tubulin concentrations. We find the rates of GDP and GTP release (0.68 and 0.32 min-1, respectively) are sufficiently fast relative to assembly to permit GDP release, phosphorylation, and GTP binding as the sole mechanism of nucleoside-5'-diphosphate kinase action in microtubule assembly. Computer simulation studies accord with the conclusion that GDP release is rapid relative to microtubule assembly. The specific activity of the nucleoside-5'-diphosphate kinase is 1.7 nmol/min/mg of microtubular protein under the conditions studied. Pulse-chase experiments with tubulin . [14C]GDP complex and the rapidity of GDP phosphorylation by the kinase are in agreement with this scheme. Finally, it was observed that the extent and rate of microtubule assembly depends upon the [ATP]/[ADP] ratio.
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PMID:Nucleotide release from tubulin and nucleoside-5'-diphosphate kinase action in microtubule assembly. 22 18

Recent advances in the studies of the aggregation of G-actin monomers, containing one molecule of ATP, to long filaments of F-actin, with a concomitant hydrolysis of the nucleotide to ADP, are reviewed. With the aid of omega-ATP, the association and dissociation rate constant of the nucleotide could be determined. The binding of the nucleotide is enhanced by the binding of one Ca++ ion, probably at a different site. The delta G value of the Mg++ or Ca++ induced polymerization has been determined to --39 to--59 kJ/mole, the critical protein concentration for the ATP-G-actin to ADP-F-actin conversion is very strongly influenced by the concentration of bivalent cations. The rate constants of the protein monomers, and the rate and equilibrium constants for the propagation step show the process to be extremely cooperative. Actin shows the interesting phenomenon of translocational head-to-tail polymerization, which may be regulated by ATP. The contact sites between the monomers in F-actin have been labeled by chemical modification. Two tryosine residues, 53 and 69, are probably close to one of the two sites. The ATP binding sites has been labeled by an ATP analog, and there is evidence that it is close to the contact site.
Mol Cell Biochem 1977 Nov 25
PMID:The polymerization reaction of muscle actin. 34 Sep 37

The kinetic and regulatory properties of purified rat heart AMP deaminase were investigated. In the presence of 100 mM KCl, the enzyme exhibited a slightly sigmoid-shaped plot of reaction rate, vs. substrate concentration, which shifted to a more hyperbolic form when ATP, ADP or GTP were added. ATP was the most potent activator of the enzyme, whereas GTP at low (less than 0.25 mM) concentrations increased the enzyme activity. The activation effect was negligible at higher concentrations of GTP. The calculated value of K0.5 of approx. 3 mM for unactivated enzyme decrased to approx. 0.6 mM and 1.1 mM when 0.5 mM ATP or 1.5 mM ADP were present in the incubation mixture, respectively. The theoretical model (Monod, J., Wyman, J. and Changeux, J.P. (1965) J. Mol. Biol. 12, 88-118) gave a partial explanation of these results.
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PMID:Regulatory properties of rat heart AMP deaminase. 44 47

Glucose-6-phosphate dehydrogenase was purified to homogeneity from testes and kidneys of the inbred strain of mice (DBA/2J) by a simple two-step affinity column procedure. This involved the sequential application of 8-(6-aminohexyl)-amino-AMP- and -2', 5'-ADP-Sepharose columns and biospecific elution with NADP+ in both steps. The molecular and biochemical properties of the purified enzyme were studied in detail. These include the molecular weight determination, amino acid composition, steady-state kinetics, inactivation by high temperature, urea and iodoacetate, and immunology. The purified enzyme from mouse kidneys or testes was shown to be a tetramer with a molecular weight of 220,000. The enzyme is highly specific for glucose-6-phosphate, exhibits almost no activity with NAD+ as a coenzyme and is little inhibited by AMP or ATP. Michaelis constants for glucose-6-phosphate and NADP+ were determined to be 50 microM and 10 microM respectively. NADPH is a competitive inhibitor of NADP+ and has a Ki of 18 microM. Rabbit antisera against glucose-6-phosphate dehydrogenase were raised. The antisera also cross-react with the same enzyme from human and guinea pig.
Mol Cell Biochem 1979 Mar 19
PMID:Purification and characterization of mouse glucose 6-phosphate dehydrogenase. 46 Jan 73

When tested in a poly(U)-dependent polyphenylalanine synthesizing system and in a postnuclear supernatant, both derived from Ehrlich ascites tumor cells, 2'(3'),5'-ADP did not affect chain elongation of polypeptide synthesis. In a cell-free system which was dependent on initiation and programmed by natural mRNA, however, the amino acid incorporating activity was suppressed to about 10% of the control in the presence of 1 mM 2'(3'),5'-ADP. The inhibitor was shown not to interfere with the attachment of poly(U) to the small ribosomal subunit and with the formation of mRNA-80S ribosome complexes in a complete protein synthesizing system. The subsequent attachment of a 40S ribosomal subunit to the mRNA-80S ribosome complex and the formation of polysomes, however, was depressed by the inhibitor. The experimental results suggest that 2',(3'),5'-ADP inhibits initiation-dependent protein synthesis between monosome formation and the formation of the first peptide bond(s).
Mol Biol Rep 1977 Jun
PMID:2'(3'),5'-ADP inhibits initiation-dependent protein synthesis in a cell-free system from Ehrlich ascites tumor cells. 56 Jun 26

Gluconeogenesis by isolated hepatocytes resulted in glucose release but insignificant rates of glycogen synthesis. The effectiveness of precursors was similar for hepatocytes from fed and starved chickens except for impaired gluconeogenesis from pyruvate when compared to lactate in lactate starved chicken hepatocytes. The impairment was caused by limitations in cytosolic NADH production as a result of the mitochondrial location of phosphoenolpyruvate carboxykinase in chicken liver. The order of effectiveness of precursors on hepatic gluconeogenesis was generally similar to the effects of precursors on increasing the plasma glucose concentration in vivo. The exceptions were caused by interactions with other precursors in vivo. The alteration of the NADH/NAD+ ratio by ethanol and ATP/ADP ratio by adenosine could play significant roles in the control of precursor conversion to glucose. Physiological glucagon concentrations stimulated gluconeogenesis from precursors entering the pathway both above and below the level of triose phosphates, and its effect were mimicked by dibutyryl cyclic AMP. Previous results on the effects of precursor and glucagon injection on the plasma glucose concentration of chickens in vivo can largely be explained by effects at the hepatic level. Isolated chicken and rat hepatocytes share many common features. Qualitatively the ordering of gluconeogenic effectiveness was similar but quantitive differences existed as a result of differing activities and cellular locations of enzymes. Neither preparation readily synthesised glycogen and the sensitivity to glucagon was similar.
Mol Cell Biochem 1978 Dec 22
PMID:Hepatic gluconeogenesis in chickens. 74 98

1. The regulatory properties of two interconvertible kinetic forms of class A pyruvate kinase from Ehrlich ascites tumor cells have been studied with a partially purified enzyme preparation free of interfering enzymatic activities. 2. The hyperbolic form shows Michaelis-Menten kinetics for P-pyruvate, with high affinity for this substrate and low affinity for the inhibitory amino acids alanine and phenylalanine. The sigmoidal form displays positive cooperativity respect to P-pyruvate (n=1.4), with lower affinity for this substrate and higher affinity for the inhibitory amino acids. 3. The equilibrium between the hyperbolic and the sigmoidal forms of the enzyme is affected by substraetes and effectors. P-pyruvate, ADP and Fru-P2 shift the equilibrium to the hyperbolic form while ATP, alanine and phenylalanine stabilize the sigmoidal form. 4. Effector metabolites affect the molecular weight of the protein, acting on an equilibrium between dimers and tetramers. P-pyruvate and ADP associate the enzyme to a tetramer while ATP, alanine and phenylalanine favor the occurrence as a dimer. The positive modifier Fru-P2 did not associate the enzyme to the tetramer, even at 1 mM concentration. 5. A tentative molecular model for pyruvate kinase A on the basis of the kinetic and aggregation interconversion is proposed.
Mol Cell Biochem 1976 Oct 30
PMID:Interconversion phenomena between two kinetic forms of class a pyruvate kinase from Ehrlich ascites tumor cells. 100 94

1. Two women with severe hypokalaemic alkalosis were investigated by means of muscle biopsy before and at the end of 2 and 3 weeks respectively of intense therapy with potassium chloride. 2. The muscle biopsy material was analysed for water, electrolytes, adenine nucleotides, phosphocreatine, free creatine, pyruvate, lactate, glycogen and free amino acids. The extra- and intra-cellular distribution of water, electrolytes and amino acids was calculated by the chloride method. 3. Both patients showed a marked loss of intracellular potassium and an increase in intracellular sodium concentration. The muscle magnesium content was also slightly decreased. After repletion with potassium chloride, muscle sodium and potassium became normal. 4. The contents of creatine phosphate, ATP, ADP, AMP, lactate and pyruvate were within normal limits, but the phosphocreatine/total creatine ratio was reduced. After repletion, a small change in the apparent creatine-phosphokinase equilibrium had occurred, suggesting a minor increase in intracellular pH. 5. The concentrations of the basic amino acids, lysine, arginine and ornithine were increased far above normal. The intracellular accumulation of arginine was much higher than the increase in lysine concentration and histidine concentration was normal. This differs from findings in potassium-depleted rats, where the intracellular lysine concentration is much higher than arginine concentration and histidine is high as well. After potassium repletion the intracellular concentration of ornithine, lysine and arginine became normal in one case and decreased considerable in the other. An increased intracellular concentration of glutamate and glutamine was also observed after potassium repletion.
Clin Sci Mol Med 1976 Dec
PMID:Influence of severe potassium depletion and subsequent repletion with potassium on muscle electrolytes, metabolites and amino acids in man. 107 Apr 23

1. Long-chain acid: CoA ligase (AMP-forming) (trivial name acyl-CoA synthetase; EC 6.2.1.3) is located at the membranes of the endoplasmic reticulum and the outer membrane of the mitochondria. The latter membrane has by far the highest specific activity. 2. GTP-dependent synthesis of acyl-CoA has a very low activity in liver mitochondria (about 5% of the activity measured with ATP). CTP, ITP, UTP and GTP may all provide energy for fatty acid activation in sonicated mitochondria by formation of ATP from endogenous ADP and AMP. 3. In rat liver palmitoyl-CoA: L-carnitine O-palmitoyltransferase (trivial name carnitine palmitoyltransferase; EC 2.3.1.21) is located at the microsomal membranes and in the inner membrane of the mitochondria. Its activity is increased, in both membranes, during fasting and in thyroxine-treated rats. The extramitochondrial carnitine palmitoyltransferase may capture part of the acyl CoA formed at the endoplasmic reticulum as acyl-carnitine, especially during fasting and other metabolic conditions of high fatty acid turnover. This transport form of activated fatty acid can penetrate the inner mitochondrial membrane (the acyl-CoA barrier) where it can be reconverted to acyl-CoA, providing the substrate for beta-oxidation in the inner membrane-matrix compartment. The small part of the mitochondrial carnitine palmitoyltransferase, described to be present at the external surface of the mitochondrial inner membrane, may have the same function in the transport of acyl-CoA formed at the mitochondrial outer membrane. 4. Isolated rat liver mitochondria can oxidize high concentrations of palmitate or oleate in the absence of carnitine. In this case the fatty acids are activated in the inner membrane-matrix compartment of the mitochondria, probably by a medium-chain acyl-CoA synthetase with wide substrate specificity. Because this enzyme is less active in heart and absent in skeletal muscle, these tissues oxidize long-chain fatty acids in an obligatory carnitine-dependent fashion. Also the liver oxidizes long-chain fatty acids in a carnitine-dependent way if lower fatty acid concentrations are used. In this tissue carnitine stimulates specifically the partial oxidation of fatty acids to beta-hydroxybutyrate and acetoacetate. 5. The activities of acyl-CoA: sn-glycerol-3-phosphate O-acyltransferase (trivial name glycerophosphate acyltransferase; EC 2.3.1.15) and carnitine palmitoyltransferase change in opposite directions during fasting. These activity changes, together with the measured kinetic properties of the enzymes in mitochondria and microsomes, allow a switch (relatively) from lipid synthesis to ketogenesis during fasting. This switch may occur at the level of long-chain acyl-CoA both in the endoplasmic reticulum and in the mitochondria.
Mol Cell Biochem 1975 Apr 30
PMID:Aspects of long-chain acyl-COA metabolism. 113 97


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