Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The regulatory properties of adenylate cyclase in small intestinal mucosa were investigated. Glucagon, epinephrine and isoproterenol failed to activate the cAMP synthesis; prostaglandin E1 caused a 2.8-fold, while cholera toxin-a 4.5-fold stimulation. The latter was not able to increase the rate of glucose synthesis from alanine in vitro, but increased markedly the in vivo incorporation of 14C-labeled alanine into the mucus glucosamine. Unlabeled glucosamine excretion was also enhanced 3-fold. This provides evidence for the involvement of glycolysis and gluconeogenesis enzyme systems in the mucosal glycoprotein synthesis. It was assumed that both metabolic pathways may play a common physiological role, namely, to convert carbohydrates and gluconeogenic precursors into the substrate for glucosamine synthesis which is thought to be a rate-limiting step in small intestinal mucus secretion.
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PMID:[Relation between glycoprotein synthesis and carbohydrate metabolism in the small intestine mucosa. Effect of cholera enterotoxin]. 283 Sep 17

Membrane vesicle preparations enriched in plasma membrane marker proteins, such as adenylate cyclase, were prepared from spermatozoa of the sea urchin, Lytechinus pictus. These membranes, prepared by nitrogen cavitation and subsequent sucrose gradient centrifugation, retained the capacity to bind [125I]-Bolton-Hunter speract (nonspecific binding was less than 5% of specific binding). Speract (Gly-Phe-Asp-Leu-Asn-Gly-Gly-Gly-Val-Gly), Tyr-Asp-Leu-Asn-Gly-Gly-Gly-Val-Gly, Tyr-Asp-Leu-Thr-Thr-Gly-Gly-Gly-Val-Gly and Gly-Phe-Ala-Leu-Gly-Gly-Gly-Val-Gly caused a 50% decrease in [125I]-Bolton-Hunter speract binding at 10, 600, 1260 and 3160 nM concentrations, respectively. One analogue (Phe-Asp-Leu-Asn-Gly-Gly-Gly), which had no biological activity, failed to compete at concentrations as high as 10 microM. To demonstrate that the binding was due to the isolation of membranes with an intact receptor, the speract analogue (Gly-Gly-Gly-Gly-Tyr-Asp-Leu-Asn-Gly-Gly-Gly-Val-Gly) was synthesized, radiolabeled with 125I at the position of tyrosine, and covalently cross-linked to the receptor with disuccinimidyl suberate. A single radiolabeled band at an apparent molecular weight of 77,000 was detected on Na X dodecyl X SO4 gels. These studies are the first to identify a receptor for egg-associated peptides in isolated spermatozoan membranes.
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PMID:Retention of the speract receptor by isolated plasma membranes of sea urchin spermatozoa. 300 10

Polylysine-containing peptides are found to affect membrane protein kinases, phosphatidylinositol kinases, and adenylate cyclase. Poly(L-lysine), poly(D-lysine), random copolymers of lysine and serine or lysine and alanine, and poly(L-ornithine) produced large increases in the in vitro phosphorylation of some membrane proteins present in Xenopus laevis oocyte membranes. Poly(L-arginine) did not cause a similar stimulation. In these membranes the phosphorylation of polydisperse protein of approximately 25 kDa was also greatly increased by 1 mM spermine and spermidine, by 10 microM histone H1, or by 200 microM peptide containing the 14-residue sequence at the carboxyl terminus of the human c-Ki-ras 2 gene product, which has eight lysines. Similar specific stimulation of protein phosphorylation was observed with membranes of NG-108-15 nerve cells in culture. Polylysine peptides, including the c-Ki-ras 2 segment, also stimulate the in vitro phosphorylation of membrane inositolphospholipids, to produce mainly phosphatidylinositol 4-phosphate and less phosphatidylinositol 4,5-bisphosphate. Polylysine also alters the activity of oocyte adenylate cyclase, assayed in the presence of either F- or 5'-guanylyl imidodiphosphate.
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PMID:Polylysine-containing peptides, including the carboxyl-terminal segment of the human c-Ki-ras 2 protein, affect the activity of some key membrane enzymes. 302 67

Vanadate has been reported to inhibit (Na+ + K+)-ATPase of many cells and in some systems to stimulate adenylate cyclase. Since intestinal transport is influenced by these enzymes, we studied the effects of varying concentrations of orthovanadate (VO-4) on alanine transport in the in vitro rat jejunum. At the higher concentrations tested (10(-3) and 10(-2) M) vanadate had a ouabainlike action on alanine transport. It decreased the mucosal-to-serosal flux and the influx of alanine into the intestinal epithelium and it caused a reduction of (Na+ + K+)-ATPase activity of basolateral membranes. The relatively lower vanadate concentration of 10(-4) M increased the influx and the efflux of alanine across the mucosal border of the jejunum. The increase was associated with elevation of cyclic AMP in the intestinal mucosa. The studies suggest the presence of a dual action of vanadate on amino acid transport, a stimulatory effect at low concentration, due to increased adenylate cyclase activity, and an inhibitory effect at higher concentrations, due to a decreased activity of (Na+ + K+)-ATPase.
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PMID:Effect of vanadate on amino acid transport in rat jejunum. 303 89

Escherichia coli NCR91 synthesizes a mutant form of catabolite gene activator protein (CAP) in which alanine 144 is replaced by threonine. This mutant, which also lacks adenylate cyclase activity, has a CAP phenotype; in the absence of cAMP it is able to express genes that normally require cAMP. CAP91 has been purified and crystallized with cAMP under the same conditions as used to crystallize the wild type CAP X cAMP complex. X-ray diffraction data were measured to 2.4-A resolution and the CAP91 structure was determined using initial model phases from the wild type structure. A difference Fourier map calculated between CAP91 and wild type showed the 2 alanine to threonine sequence changes in the dimer and also a change in orientation of cysteine 178 in one of the subunits. The CAP91 coordinates were refined by restrained least squares to an R factor of 0.186. Differences in the atomic positions of the wild type and mutant protein structures were analyzed by a vector averaging technique. There were small changes that included concerted motions in the small domains, in the hinge between the two domains and in an adjacent loop between beta-strands 4 and 5. The mutation at residue 144 apparently causes changes in the position of some protein atoms that are distal to the mutation site.
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PMID:Crystal structure of a cyclic AMP-independent mutant of catabolite gene activator protein. 303 40

1. The membrane potential of mouse beta-cells was measured in parallel with 86Rb+ efflux and insulin release from mouse islets during stimulation by three types of amino acids and modulation of their effects by glucose and cyclic adenosine monophosphate (cyclic AMP) (forskolin being used to activate the adenylate cyclase). 2. In the absence of glucose, alanine and arginine accelerated 86Rb+ efflux, whereas leucine decreased it. They all depolarized the beta-cell membrane and slightly increased insulin release. Forskolin had little effect on 86Rb+ efflux, consistently potentiated insulin release but induced electrical activity only in the presence of leucine. 3. The effects of the three amino acids on 86Rb+ efflux and beta-cell membrane potential were not qualitatively altered by a non-stimulatory concentration of glucose (3 mM). However, the release of insulin induced by leucine alone or with forskolin was markedly amplified, in contrast to that of alanine or arginine, which was inhibited. 4. In the presence of a threshold concentration of glucose (7 mM), the three amino acids accelerated 86Rb+ efflux and depolarized the beta-cell membrane. With alanine and arginine, spike activity was transiently observed and coincided with a short-lived increase in insulin release. With leucine, slow waves with superimposed bursts of spikes occurred and were accompanied by a sustained release of insulin. Forskolin alone also triggered slow waves and bursts of spikes, and increased insulin release. Both effects were larger in the presence of arginine, but not in the presence of alanine. Forskolin considerably increased the electrical and secretory effects of leucine. 5. A higher concentration of glucose (10 mM) induced slow waves with bursts of spikes in all cells and stimulated insulin release. Alanine, arginine and leucine increased 86Rb+ efflux, electrical activity and insulin release. However, the changes produced by the three amino acids displayed different time course, amplitude and characteristics. Forskolin potentiated insulin release and electrical activity induced by glucose alone. These effects were not augmented by alanine, but markedly amplified by arginine or leucine. 6. Several conclusions can be drawn from this study. The three types of amino acids depolarize the beta-cell membrane by different mechanisms and produce distinct patterns of electrical activity. Slow waves with bursts of spikes occur only if a decrease in K+ permeability contributes to the depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cyclic adenosine monophosphate differently affects the response of mouse pancreatic beta-cells to various amino acids. 304 Sep 64

GTP-binding regulatory proteins (G-proteins) were identified in chemosensory membranes from the channel catfish, Ictalurus punctatus. The common G-protein beta-subunit was identified by immunoblotting in both isolated olfactory cilia and purified taste plasma membranes. A cholera toxin substrate (Mr 45,000), corresponding to the G-protein that stimulates adenylate cyclase, was identified in both membranes. Both membranes also contained a single pertussis toxin substrate. In taste membranes, this component co-migrated with the alpha-subunit of the G-protein that inhibits adenylate cyclase. In olfactory cilia, the Mr 40,000 pertussis toxin substrate cross-reacted with antiserum to the common amino acid sequence of G-protein alpha-subunits, but did not cross-react with antiserum to the alpha-subunit of the G-protein from brain of unknown function. The interaction of G-proteins with chemosensory receptors was determined by monitoring receptor binding affinity in the presence of exogenous guanine nucleotides. L-Alanine and L-arginine bind with similar affinity to separate receptors in both olfactory and gustatory membranes from the catfish. GTP and a nonhydrolyzable analogue decreased the affinity of olfactory L-alanine and L-arginine receptors by about 1 order of magnitude. In contrast, the binding affinities of the corresponding taste receptors were unaffected. These results suggest that olfactory receptors are functionally coupled to G-proteins in a manner similar to some hormone and neurotransmitter receptors.
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PMID:Interaction of GTP-binding regulatory proteins with chemosensory receptors. 310 71

Isolated sheep hepatocytes were used to obtain estimates of kinetic parameters, identify substrate preference and interactions and study regulation of gluconeogenesis. Respective Vmax estimates for propionate, pyruvate and alanine conversion to glucose were 59.5, 12.8 and 21.5 mol glucose formed X (h X g dry weight)-1. Respective KS estimates for propionate and pyruvate were 1 mM and 18 to 40 microM. Rates of lactate utilization varied among cell preparations, possibly because of loss of lactate dehydrogenase during isolation. Dihydroxyacetone and glycerol were utilized for glucose synthesis at similar rates of 8.6 and 8.7 mumol glucose formed X (h X g dry weight)-1, respectively. Respective rates of glucose synthesis from 5 mM fructose and 10 mM galactose were 63.2 and 31.4 mumol X (h X g dry weight)-1. Maximum rates of pyruvate carboxylase and phosphoenolpyruvate carboxykinase were estimated to be 101.6 and 160.4 mumol substrate converted X (h X g dry weight)-1, respectively. Neither butyrate nor acetate accelerated gluconeogenesis from propionate while acetate increased glucose synthesis from pyruvate, presumably through activation of pyruvate carboxylase. Glucagon stimulated gluconeogenesis from propionate. Dibutyrylcyclic AMP mimicked the effect of glucagon, implying that the glucagon effect is translated via the adenyl cyclase system as in rats. The kinetic parameters established in these experiments should be useful in future experiments and in computer modeling analyses of ruminant liver and whole animal metabolism where Michaelis-Menten type equations are widely used.
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PMID:Gluconeogenesis in isolated lamb hepatocytes. 381 90

In the presence of DL-alanine intracellular cyclic AMP in nonproliferating cells of Brevibacterium liquefaciens increased rapidly to the maximum level of approximately 180 muM, and extracellular cyclic AMP increased to 100 muM within 4 hr at 25 degrees . Adenylate cyclase (EC 4.6.1.1) induction was not observed during this incubation. The concentration of pyruvate in the total culture increased concomitantly with that of cyclic AMP and reached approximately 20 mM after 4 hr of incubation. Since the activity of cyclic nucleotide phosphodiesterase is extremely low in this bacterium, the accumulation of cyclic AMP with DL-alanine appeared to be due to the activation of adenylate cyclase by pyruvate. D-alanine was more effective than L-alanine in producing pyruvate, and a high activity of D-alanine oxidation was detected in the cell lysate of B. liquefaciens.Thus, adenylate cyclase in this bacterium appeared to be regulated in vivo by pyruvate which was formed, in this case, predominantly from D-alanine through the action of D-aminoacid oxidase (EC 1.4.3.3). Pyruvate, added extracellularly, also caused a rapid accumulation of intracellular cyclic AMP. Glucose did not change the level of cyclic AMP significantly. It also did not affect the intracellular accumulation of cyclic AMP with DL-alanine.
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PMID:Adenylate cyclase from Brevibacterium liquefaciens. III. In situ regulation of adenylate cyclase by pyruvate. 437 21

The formation of adenosine cyclic 3',5'-phosphate by Brevibacterium liquefaciens ATCC 14929 was studied with the use of nonproliferating cells and cell-free extract. With nonproliferating cells provided by deprivation of sulfate, the formation of this nucleotide was accelerated by adding some amino acids and sugars. Among amino acids tested, alanine and asparagine were most effective. Pentoses were more favorable than hexoses and other sugars. Formation of adenosine cyclic 3',5'-phosphate was observed also with chloramphenicol-treated cells. Experiments on cell-free extract showed that addition of alanine or pyruvate stimulated the formation of adenosine cyclic 3',5'-phosphate from adenosine-5'-triphosphate. When alanine was added to the cell-free system, shaking of the reaction mixture further increased the amount of the nucleotide, but pyruvate was far more effective than alanine. No synergistic effect of alanine and pyruvate was observed. Some enzyme activity was observed which decomposed adenosine cyclic 3',5'-phosphate, but it was weak as compared with adenyl cyclase activity in the presence of pyruvate. From the results obtained, it appears that pyruvate may act as an activating factor of adenyl cyclase in Brevibacterium liquefaciens.
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PMID:Formation of adenosine cyclic 3',5'-phosphate by nonproliferating cells and cell-free extract of Brevibacterium liquefaciens. 603 54


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