Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Independently obtained mutations (apt) of resistance to DAP (2,6-diaminopurine) and MP (6-methylpurine), that affect adenine phosphoribosyltransferase (APRT) in Escherichia coli, are different in their effect on the conversion of several substrates of APRT, such as DAP, MP, MAP (6-methylaminopurine) and adenine, to their nucleotide derivatives. Most of mutants were resistant to DAP and MP, unable to utilize MAP (as purine source) and differed in their ability to uptake adenine from the medium. Among the mutants capable to utilize adenine the following types are found: (1) resistant to DAP and MP, but capable of utilizing MAP, and (2) resistant to DAP, capable of utilizing MAP, but sensitive to MP. The gene apt encoding APRT is located between genes proC and purE; the frequency of cotransduction between proC and several apt mutations is found to be 1.7--2% and purE-apt--to be 5--10.8%. Mutations apt block up the ability of purine-dependent (pur) bacteria lacking purine nucleoside phosphorylase (pup) to use purine ribonucleosides as purine sources. The degree of that blocking depends on the ability of apt mutants to convert adenine to AMP via APRT. These observations confirm our previous data, that the ability of pur pup mutants to use purine ribonucleosides depends on the activity of APRT.
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PMID:[Mutations of resistance to 2,6-diaminopurine and 6-methylpurine that affect adenine phosphoribosyltransferase in Escherichia coli K-12]. 34 74

(1) RNase Ms was inactivated by iodoacetate. The inactivation was most rapid at pH 6.0, and was inhibited in the presence of a denaturant such as 8 m urea or 6 m guanidine-HCL. (2) Competitive inhibitors protected RNase Ms from inactivation by iodoacetate; the effect was in the order 2',(3')-GTP greater than 2',(3')-AMP, 2',(3')-UMP greater than or equal to 2',(3')-CMP. The order is not consistent with that of the binding constants of the 4 nucleotides towards RNase Ms (A is greater than C greater than G greater than U). (3) RNase Ms was inactivated with the concomitant incorporation of one molar equivalent of carboxymethly group. The following evidence indicated that the carboxymethyl group was incorporated into the carboxyl group of an aspartic acid or glutamic acid residue. (i) The carboxymethyl group incorporated into RNase Ms was liberated by treatment with 0.1 n NaOH or 1 m hydroxylamine. (ii) The amino acid composition of carboxymethylated RNase Ms (CM RNase Ms) after acid hydrolysis is similar to that of RNase Ms. (4) 14C-Labeled CM RNase Ms was digested successively with alkaline protease and amino-peptidase M. The radioactive amino acid released was eluted just before aspartate on an amino acid analyzer. After hydrolysis with 6 n HCL, glutamic acid was produced exclusively from the radioactive amino acid. The specific radioactivity of this amino acid calculated from the radioactivity and glutamic acid formed was practctically the same as that of CM RNase Ms. Thus, it was concluded that a carboxymethyl group was incorporated at the carboxyl group of a glutamic acid residue of RNnase Ms. (5) CM RNase Ms bound with 2'-AMP to the same extent as native RNase Ms, but bound to a lesser extent with 2',(3')-GMP. (6) Although the conformation of CM RNase Ms as judged from the CD spectrum was practically the same as that of native RNase Ms, the reactivity of CM RNase Ms towards dinitrofluorobenzene was different from that of native RNase Ms, indicating some difference in the conformation. (7) These results indicate that one glutamic acid residue is involved in the active of RNase Ms.
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PMID:Carboxymethylation of a minor ribonuclease from Aspergillus saitoi. 47 29

Using a bipolar suction electrode technique, right atrial monophasic action potential (RA MAP) was recorded in 18 patients surely free from any kind of arrhythmia. Two morphologically different kinds of RA AMP were obtained: the former exhibiting an evident transition between phase 1-2 (plateau) and phase 3 of repolarization (FP), the latter without any appreciable palteau (FL). Electrophysiological properties of human myocardial atrial tissue have been investigated by microelectrode technique. The two types of MAP recorded by us resemble the former the action potential obtained from conducting specialized fiber, the latter the action potential of contractile fibers. A statistically significant difference in RA MAP duration measured at 90% level of repolarization (D 90%) was found between the two kinds of MAP: therefore we suggest to perform quantitative evaluations and pharmaco-ogical investigations only including MAPs of similar morphology. The intraindividual variation coefficient of D 90% may be considered an expression of the range of variability of repolarization duration in man; we suggest that only MAPs of similar configuration should be accepted for its calculation in order to avoid errors of evaluation.
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PMID:[Recording of the right atrial monophasic action potential in humans. I. Subjects not affected by arrhythmia]. 66 16

Kinesin from porcine brain was prepared by a procedure based on the strong binding of the protein to microtubules in the presence of sodium fluoride and ATP. The protocol reduces the requirement for taxol and AMP-PNP. The kinesin is active in terms of its ability to move microtubules on glass slides and its ATPase. The ATPase of this kinesin is about 8 nmol/min/mg; it is activated to 19 nmol/min/mg in the presence of microtubules. The relationship between gliding velocity and ATP concentration follows Michaelis-Menten kinetics. Using the motility assay, the maximal velocity is 0.78 micron/sec, and the Km value is 150 microM for ATP. For GTP the corresponding values are 0.38 micron/sec and 1.7 mM. ADP is a competitive inhibitor (Ki = 0.29 mM). Crude preparations of kinesin do not support motility on glass slides, whereas gel-filtered kinesin does. A search for potential inhibitory factors showed that one of them is MAP2; however, its inhibitory effect becomes visible only in certain conditions. MAP2 bound to microtubules does not inhibit kinesin-induced motility. However, when MAP2 and kinesin are preadsorbed to the glass surface independently of microtubules, MAP2 prevents the interaction of kinesin with microtubules, as if it formed a "lawn" that acted as a spacer and thus repelled the MAP-free microtubules or crosslinked the MAP-containing ones. The repelling effect of MAP2 domains (projection or assembly fragments obtained by chymotryptic cleavage) added separately is less pronounced and can be overcome by kinesin. These results reinforce the view of MAP2 as a spacer molecule.
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PMID:Interaction between kinesin, microtubules, and microtubule-associated protein 2. 253 84

A reconstituted system for examining directed organelle movements along purified microtubules has been developed. Axoplasm from the squid giant axon was separated into soluble supernatant and organelle-enriched fractions. Movement of axoplasmic organelles along MAP-free microtubules occurred consistently only after addition of axoplasmic supernatant and ATP. The velocity of such organelle movement (1.6 micron/sec) was the same as in dissociated axoplasm. The axoplasmic supernatant also supported movement of microtubules along a glass surface and movement of carboxylated latex beads along microtubules at 0.5 micron/sec. The direction of microtubule movement on glass was opposite to that of organelle and bead movement on microtubules. The factors supporting movements of microtubules, beads, and organelles were sensitive to heat, trypsin, AMP-PNP and 100 microM vanadate. All of these movements may be driven by a single, soluble ATPase that binds reversibly to organelles, beads, or glass and generates a translocating force on a microtubule.
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PMID:Organelle, bead, and microtubule translocations promoted by soluble factors from the squid giant axon. 257 87

While the importance of receptor-mediated intracellular cyclic AMP in blood pressure regulation is well documented, few studies have evaluated the physiologic relevance of cyclic AMP exported from cells. We report evidence of a relationship between blood pressure and the transport of intracellular cyclic AMP from lymphocytes. Twenty-eight hypertensive and 56 normotensive white and black volunteers (mean age 40 years) were studied. Both intra- and extracellular concentrations of cyclic AMP were determined in lymphocytes following incubation with 10(-5) M isoproterenol. Compared to normotensives, hypertensives (p = 0.001), particularly white hypertensives (p = 0.023) had higher levels of exported cyclic AMP. These values were independent of intracellular concentrations of cyclic AMP, which were similar across the groups. Exported cyclic AMP was independent of both sodium excretion and beta-adrenergic receptor sensitivity, the latter being lower in white hypertensives (p = 0.024). Across all subjects, exported cyclic AMP was correlated with MAP (r = .39, p < 0.001). These findings indicate that the active transport of cyclic AMP may be enhanced in hypertension and suggest a possible pathway which might explain existing data of increased cyclic AMP levels in hypertension.
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PMID:Cyclic AMP export from lymphocytes in hypertension. 785 62

While testing purines related to the non-specific protein kinase inhibitors N6-dimethylaminopurine and N6-(delta 2-isopentenyl)adenine as potential inhibitors of the p34cdc2/cyclin B kinase, we discovered a compound with high specificity, 2-(2-hydroxyethylamino)-6- benzylamino-9-methylpurine (olomoucine). Kinetic analysis of kinase inhibition reveals that olomoucine behaves as a competitive inhibitor for ATP and as a non-competitive inhibitor for histone H1 (linear inhibition for both substrates). The kinase specificity of this inhibition was investigated for 35 highly purified kinases (including p34cdk4/cyclin D1, p40cdk6/cyclin D3, cAMP-dependent and cGMP-dependent kinases, eight protein kinase C isoforms, calmodulin-dependent kinase II, myosin light-chain kinase, mitogen-activated S6 kinase, casein kinase 2, double-stranded RNA-activated protein kinase, AMP-stimulated kinase, eight tyrosine kinases). Most kinases are not significantly inhibited. Only the cell-cycle regulating p34cdc2/cyclin B, p33cdk2/cyclin A and p33cdk2/cyclin E kinases, the brain p33cdk5/p35 kinase and the ERK1/MAP-kinase (and its starfish homologue p44mpk) are substantially inhibited by olomoucine (IC50 values are 7, 7, 7, 3 and 25 microM, respectively). The cdk4/cyclin D1 and cdk6/cyclin D3 kinases are not significantly sensitive to olomoucine (IC50 values greater than 1 mM and 150 microM, respectively). N6-(delta 2-Isopentenyl)adenine is confirmed as a general kinase inhibitor with IC50 values of 50-100 microM for many kinases. The purine specificity of cyclin-dependent kinase inhibition was investigated: among 81 purine derivatives tested, only C2, N6 and N9-substituted purines exert a strong inhibitory effect on the p34cdc2/cyclin B kinase. An essentially similar sensitivity to this olomoucine family of compounds was observed for the brain-specific cdk5/p35 kinase. Structure/activity relationship studies allow speculation on the interactions of olomoucine and its analogues with the kinase catalytic subunit. Olomoucine inhibits in vitro M-phase-promoting factor activity in metaphase-arrested Xenopus egg extracts, inhibits in vitro DNA synthesis in Xenopus interphase egg extracts and inhibits the licensing factor, an essential replication factor ensuring that DNA is replicated only once in each cell cycle. Olomoucine inhibits the starfish oocyte G2/M transition in vivo. Through its unique selectivity olomoucine provides an anti-mitotic reagent that may preferentially inhibit certain steps of the cell cycle.
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PMID:Inhibition of cyclin-dependent kinases by purine analogues. 792 96

Growth factors and cyclic AMP (cAMP) are known to activate distinct intracellular signaling pathways. Fibroblast growth factor (FGF) activates ras-dependent kinase cascades, resulting in the activation of MAP kinases, whereas cAMP activates protein kinase A. In this study, we report that growth factors and cAMP act synergistically to stimulate proenkephalin gene expression. Positive synergy between growth factor- and cAMP-activated signaling pathways on gene expression has not been previously reported, and we suggest that these synergistic interactions represent a useful model for analyzing interactions between these pathways. Transfection and mutational studies indicate that both FGF-dependent gene activation and cAMP-dependent gene activation require cAMP response element 2 (CRE-2), a previously characterized cAMP-dependent regulatory element. Furthermore, multiple copies of this element are sufficient to confer FGF regulation upon a minimal promoter, indicating that FGF and cAMP signaling converge upon transcription factors acting at CRE-2. Among many different ATF/AP-1 factors tested, two factors, ATF-3 and c-Jun, stimulate proenkephalin transcription in an FGF- or Ras-dependent fashion. Finally, we show that ATF-3 and c-Jun form heterodimeric complexes in SK-N-MC cells and that the levels of both proteins are increased in response to FGF but not cAMP. Together, these results indicate that growth factor- and cAMP-dependent signaling pathways converge at CRE-2 to synergistically stimulate gene expression and that ATF-3 and c-Jun regulate proenkephalin transcription in response to both growth factor- and cAMP-dependent intracellular signaling pathways.
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PMID:Fibroblast growth factor and cyclic AMP (cAMP) synergistically activate gene expression at a cAMP response element. 793 70

Two analyzed cases of Ethylamphetamine (EAMP) were reported. By using HPLC with a chiral column, racemic (d, l)-EAMP were detected from the urine of a Japanese male and an anorectic drug, which had been possessed by a Thai club hostess. From the urine of the former, d-MAMP, d-AMP and l-MAP were also detected. EAMP is now categorized to be one of psychotropic drugs in Japan, but not under the strict control of Psychostimulants Law. In near future, because of the similar action to stimulant drugs, EAMP will be apprehensive of the abuse in Japan.
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PMID:[Optical isomer analysis of ethylamphetamine from human urine and an anorectic drug, Apetinil Depo]. 837 75

Endotoxin shock not only causes renal failure, endotoxemia also leads to metabolic impairment, resulting in energy shortage and loss of cellular integrity; therefore, we tested the hypothesis that early changes in renal metabolism contribute to the development of acute renal failure during endotoxin shock. Endotoxin (Escherichia coli 127B8; 8 mg/kg from t = 0 to 60 min) was infused in three groups of 8 rats, in which renal biopsies were taken at t = 30, 50 and 90 min, respectively; a fourth group (n = 8) served as control. In the biopsies, glucose, lactate, ATP, ADP, AMP and creatine phosphate concentrations were determined. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured from the clearances of 131I-hippurate and 125I-thalamate, respectively. We also assayed urine flow (V; catheter in the bladder), cardiac output (CO), blood pressure (MAP), heart rate (HR) and arterial lactate, glucose and creatinine concentrations. During the first 30 min of endotoxemia, we found no systemic hemodynamic or biochemical changes. From t = 30 to t = 90, CO and MAP decreased to 59 and 70%, respectively, while HR and serum levels rose to 110 and 800%, respectively (p < 0.05), indicating progression of shock. Renal function clearly deteriorated from t = 30; at t = 90 RPF, GFR and V had decreased by 86, 84 and 86%, respectively, plasma creatinine being 193% of the baseline value (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Development of renal failure in endotoxemic rats: can it be explained by early changes in renal energy metabolism? 841 98


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