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

Using gel filtration chromatography, we find a single peak of deoxythymidine phosphorylating activity in Chlamydomonas reinhardti. This activity has characteristics of a thymidine kinase, in that (1) it will utilize ATP (or dATP) or CTP (or dCTP) as phosphoryl donor, but not AMP or phenyl phosphate, and (2) it is inhibited by dTTP (and less so by dTDP, dUTP, and dUDP) but is unaffected by 3'-5' cyclic AMP. Partially purified chlamydomonas thymidine kinase has a pH optimum near 8.5, and a molecular weight of 80,000 to 85,000 daltons. Kinetic studies indicate a ping-pong mechanism with a Km for thymidine of 1.5 x 10(-7) moles per liter. 5-Bromo- and 5-fluorodeoxyuridine, and to a lesser degree deoxyuridine, are competitive inhibitors, but significant phosphorylation of these nucleotides could not be demonstrated in vitro by thymidine kinase. While thymidine is phosphorylated to dTMP by crude Chlamydomonas extracts, greater than 80% of the product formed by the partially purified enzyme is dTTP. Further, the gel filtration elution position of the single deoxythymidylate kinase activity present in cell extracts coincides with that of thymidine kinase. These results suggest that a multifunctional enzyme, rather than three separate phosphorylating activities, may be responsible for dTTP formation.
Mol Gen Genet 1979 Nov
PMID:Characterization of thymidine kinase and phosphorylation of deoxyribonucleosides in Chlamydomonas reinhardti. 4 38

ATP, CTP, ADP, AMP, cyclic 3',5'-AMP (cAMP) and cyclic 3',5'-CMP (cCMP) effectively inhibited the specific binding of 125I-labelled human chorionic gonadotropin ([125I]HCG) to bovine corpus luteum cell membranes. This inhibition was observed with 2.5 X 10(-4) M to 1.0 X 10(-3) M nucleotide concentrations, regardless of the presence of a nucleotide regenerating system. Submaximal concentrations of combinations of the nucleotides were additive in inhibiting binding. The inhibition of [125I]HCG binding was observed when the nucleotides were added at the beginning of or during incubation or preincubation of the membranes with nucleotides. Preincubation of membranes with CTP and cAMP, subsequent washing and reincubation with hormone, showed time-dependent inhibition of [125I]HCG binding when the preincubation temperature was 38 degrees C but not at 4 degrees C. The concentrated supernates from nucleotides preincubated with membranes had no inhibitory effect on [125I]HCG binding to fresh membranes. In the absence of added nucleotides, [125I]HCG-membrane interaction had the following apparent binding constants: a Kd of 1.5 X 10(-10) M, 46.3 fmoles of binding sites per mg membrane protein, and rate constants for association and dissociation 4.0 X 10(6) M-1 sec-1 and 1.0 X 10(-3) sec-1, respectively. At steady state conditions of [125I]HCG binding, CTP inhibited [125I]HCG at lower concentrations of added hormone (less than 3 X 10(-9) M) whereas at higher concentrations, this nucleotide enhanced [125I]HCG binding. Scatchard analysis of the data revealed that inhibition and enhancement of [125I]HCG binding in the presence of CTP were due to lowered affinity of gonadotropin receptors (32-37) fold) and to exposure of new low-affinity binding sites for [125I]HCG, respectively. At non-steady-state conditions, nucleotides increased dissociation rates (80 to 100%) and decreased association rates (30 to 38%). The data appear to be compatible with the suggestion that the nucleotides may bind to sites in the membranes and subsequently induce conformational changes in membrane components, resulting in a decreased affinity of gonadotropin receptors. The physiological significance of these findings needs to be determined.
Mol Cell Endocrinol 1975 Oct
PMID:Mechanism of nucleotide inhibition of gonadotropin binding to cell membranes of bovine corpus luteum. 17 91

The combined phosphorylation of uridine and cytidine by a partially purified preparation of uridine-cytidine kinase has been studied with dual-substrate kinetics. The kinetic patterns obtained are consistent with the theoretical analysis for two competing, alternate substrates interacting with a single enzyme. Thus, despite feedback regulation of the kinase by both UTP and CTP, the results allow a clear conclusion that both nucleosides are phosphorylated by the same enzyme, and probably at a single site, rather than by two closely related isozymes, each specific for one pyrimidine.
Mol Cell Biochem 1977 Oct 07
PMID:Uridine-cytidine kinase. III. Competition between uridine and cytidine for a single enzyme. 20 Aug 38

Some properties of an enzyme designated as a two component ribonucleotidyl transferase from E. coli are presented. The enzyme in the presence of magnesium ions catalyzes the synthesis of polyribonucleotide chains using all four nucleoside triphosphates as substrates. The enzyme consists of two components; component A in the presence of Mg2+ catalyzes the synthesis of homo- and heteropolymers using ATP, CTP and UTP but not GTP as substrates. Component B itself does not catalyze any synthesis at all, but its addition to component A affects this component in two ways: quantitatively- the activity of component A considerably increases, and qualitatively- both components together are capable of catalyzing the synthesis of polyribonucleotides consisting of all four ribonucleotides.
Mol Biol Rep 1975 Jul
PMID:A tw0-component ribonucleotidyl transferase from E. coli. 24 Jan 21

The conformational changes in aspartate transcarbamylase upon binding of substrates or regulatory ligands and the effects of alterations in the subunit structure on the allosteric interactions are reviewed. The available information including recent results from studies of the c3r6 complex (c denotes the catalytic polypeptide and r, the regulatory polypeptide) is considered in terms of the existing models for the discrepancies between experimental observations and the present models could be resolved by postulating an important role for r:r interactions in the allosteric mechanism. A new model is presented in which an obligatory conformational change upon binding of substrates results in an alteration in the relative orientation of c versus r. As a consequence of symmetry conservation, the r:r domain is shifted to a position of higher potential energy. By favoring one or the other alternative r:r domains, CTP and ATP can respectively enhance and reduce the sigmoidal character of substrate saturation. The model is shown to be consistent with all of the important known properties of the enzyme. Because the heterotropic effects of CTP or ATP are postulated to operate via a mechanism separate from that for the homotropic effects of the substrates, this model accounts satisfactorily for the observation by Kerbiriou and Herve (Kerbiriou, D., and Herve, G. (1973) J. Mol. Biol. 78, 687-702) that homotropic effects can be abolished whereas heterotropic effects are retained in the altered enzyme from Escherichia coli grown in the presence of 2-thiouracil.
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PMID:Subunit interactions in aspartate transcarbamylase. A model for the allosteric mechanism. 108 47

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

Incorporation of [3H] uridine into the ribonucleoside triphosphates UTP and CTP, total RNA, and nuclear and cytoplasmic RNA was followed in Xenopus laevis tadpole liver during thyroxine (T4)-induced metamorphosis. Pool sizes of UTP and CTP were found to remain unchanged, although turnover the ribonucleoside triphosphates was found to be greatly stimulated after 4 days of hormone treatment. The time course of labeling of the 40-S pre-rRNA was very similar to that of UTP in both thyreostatic and T4-treated tadpoles, thus reflecting a direct relationship between turnover of the immediate precursors and labeling of RNA. Although a faster depletion of labeled UTP and pre-rRNA (precursor ribosomal RNA) was noted in T4-treated tadpoles, labeled cytoplasmic rRNA continued to accumulate almost linearly for 25 h. In thyreostatic larvae no further increase in labeled cytoplasmic rRNA occurred beyond 4 h of labeling. From these results we conclude that both enhanced transcription and more effective utilization of pre-rRNA are responsible for the net accumulation of rRNA observed on the 4th day of T4-induced metamorphosis.
Mol Cell Endocrinol 1976 Jan
PMID:Incorporation of (5-3H) uridine into ribonucleotide pools and RNA during thyroxine-induced metamorphosis of Xenopus laevis tadpoles. 124 66

The rates of phosphatidylcholine biosynthesis in the isolated hamster hearts under ischemic and hypoxic conditions were examined. Global ischemia was produced by perfusion of the heart with a reduced flow, whereas hypoxia was produced by perfusion with a N2-saturated buffer. A 51% reduction in the biosynthesis of phosphatidylcholine was observed in the ischemic heart. The reduction was caused by a severe decrease in ATP level which resulted in a diminished conversion of choline into phosphocholine. A 22% reduction in the biosynthetic rate of phosphatidylcholine was also detected in the hypoxic heart. The reduction was caused by a diminished level of CTP which resulted in a decreased conversion of phosphocholine to CDP-choline. No compensatory mechanism was triggered during ischemia, but the CTP: phosphocholine cytidylyltransferase activity was enhanced in the hypoxic heart. Our results demonstrate the possible rate-limiting role of choline kinase and reconfirm the regulatory role of the cytidylyltransferase in the biosynthesis of phosphatidylcholine.
Mol Cell Biochem 1992 Oct 21
PMID:Phosphatidylcholine metabolism in ischemic and hypoxic hearts. 133 21

Coordination of GTP and 5-aminoimidazole-4-carboxamide riboside 5'-phosphate pools changes was studied. The CTP pool is an important component of Escherichia coli metabolism, while AICAR 5'-phosphate being one of alarmones controls the synthesis of GTP. Main attention was paid to histidine, the biosynthesis of which is connected with formation of purine nucleotides. The expression of the histidine operon and biosynthesis of histidine are shown to change the AICAR pool and help the formation of the GTP pool. The ribosomal antibiotics streptomycin and chloramphenicol may cause the temporary deficiency of GTP eliminated by the increase of alarmone AICAR pool. The latter event is concluded to cause the increase in GTP pool independent of the means of AICAR accumulation (C1-pholatedependent restriction of metabolization or, vice versa, the stimulation in the histidine biosynthesis pathway).
Mol Gen Mikrobiol Virusol 1992
PMID:[The role of histidine in regulating the synthesis of purine nucleotides in Escherichia coli cells]. 162 Jan 51

The mechanism underlying the formation of easily releasable myofilaments, from myofibrils treated with an ATP-containing relaxing solution, was examined in this investigation. The proportion of releasable myofilaments purified from myofibrils of cardiac, fast- and slow-twitch muscles increased as the [ATP] was raised from 0 to 8.5 mM. The protein composition of the easily releasable myofilaments did not differ with increasing ATP concentrations as observed by 5-15% linear gradient SDS-PAGE. There is a nucleotide specificity to the release of myofilaments in the order of ATP greater than GTP much greater than UTP greater than CTP. Experiments with AMP-PNP and inorganic phosphate (Pi) showed that ATP hydrolysis and the build up of Pi are not requirements in the formation of the easily releasable myofilaments. The release of myofilaments was found to be insensitive to variations in pH from 6.5 to 7.5. The ATP stimulation of myofilaments release is ubiquitin-independent, since incubation of purified myofibrils with ubiquitin (1-100 micrograms/ml) at both 20 and 37 degrees C did not change the amount released. Modifying the free sulfhydryl group content by treatment of myofibrils with NEM (0.01-1 mM) or silver nitrate (0.1-10 mM) decreased the proportion of myofilaments that were releasable. Exclusion of 1 mM DTT from the preparation of myofibrils had similar results. These results indicate that the formation of easily releasable myofilaments can be mediated by metabolically related parameters such as the adenosine nucleotides and the reduction-oxidation status of the myofibrillar proteins of striated muscle.
Mol Cell Biochem 1991 May 15
PMID:Regulation of ATP-stimulated releasable myofilaments from cardiac and skeletal muscle myofibrils. 164 79


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