Cyclic AMP and

Many biochemical and biophysical studies of CAP-DNA complexes in solution have demonstrated that CAP induces a sharp bend in DNA upon binding. This was confirmed when the group of Thomas Steitz at Yale University determined the crystal structure of cyclic AMP-DNA complex to 3 A resolution. The CAP molecule comprises two identical polypeptide chains of 209 amino acid residues (Figure 8.24). Each chain is folded into two domains that have separate functions (Figure 8.24b). The larger N-terminal domain binds the allosteric effector molecule, cyclic AMP, and provides all the subunit interactions that form the dimer. The C-terminal domain contains the helix-tum-helix motif that binds DNA. 

FIGURE 15.20 The adenylyl cyclase reaction yields 3, 5 -cyclic AMP and pyrophosphate. The reaction is driven forward by subsequent hydrolysis of pyrophosphate by the enzyme inorganic pyrophosphatase. 

There are numerous second messenger systems such as those utilizing cyclic AMP and cyclic GMP, calcium and calmodulin, phosphoinosiddes, and diacylglerol with accompanying modulatory mechanisms. Each receptor is coupled to these in a variety of ways in different cell types. Therefore, it can be seen that it is impractical to attempt to quantitatively define each stimulus-response mechanism for each receptor system. Fortunately, this is not an... 

CREB stands for cyclic-AMP response element (CRE) binding protein and is a transcription factor. When phosphorylated by cyclic AMP- and cyclic GMP-dependent Protein Kinases or other protein kinases it binds to gene promoters that contain a specific binding site. After binding, the respective transcription activity is modulated. 

The GABAB-receptors, the muscarinic M2- and IVU-receptors for acetylcholine, the dopamine D2-, D3-and D4-receptors, the a2-adrenoceptors for noradrenaline, the 5-HTiA F-receptors for serotonin, and the opioid p-, 8- and K-receptors couple to G proteins of the Gi/o family and thereby lower [1] the cytoplasmic level of the second messenger cyclic AMP and [2] the open probability ofN- andP/Q-type Ca2+ channels (Table 1). The muscarinic Mr, M3- and M5-receptors for acetylcholine and the ai-adrenoceptors for noradrenaline couple to G proteins of the Gq/11 family and thereby increase the cytoplasmic levels of the second messengers inositol trisphosphate and diacylglycerol (Table 1). The dopamine Dr and D5-receptors and the (3-adrenoceptors for noradrenaline, finally, couple to Gs and thereby increase the cytoplasmic level of cyclic AMP. 

Interactions with caffeine and aspirin can increase the effects of ephedrine. Norepinephrine works in part by increasing the levels of cyclic aminomethyl propanol (AMP) in cells. Caffeine inhibits the enzyme that breaks down cyclic AMP. Together, ephedrine makes more cyclic AMP, and caffeine prevents it from breaking down. Aspirin inhibits the receptors that turn off release of norepinephrine. 

Edwards, J.G., Cambell, G., Carr, M Edwards, C.C. (1993). Shapes of cells spreading on fibronectin Measurement of the stellation of BHK21 cells induced by raising cyclic AMP, and of its reversal by erum and lysophosphatidic acid. J. Cell Sci. 104,399-407. 

Schoeninger, M.J. and DeNiro, M.J. 1984 Nitrogen and carbon isotopic composition of bone collagen from marine and terrestrial animals. Geochimica et Cosmochimica Acta 48 625-639. Schuette, S. A., Hegsted, M., Zemel, B. and Linkswiler, H.M. 1981 Renal acid, urinary cyclic AMP, and hydroxyproline excretion as affected by level of protein, sulfur amino acids and phosphorus intake. Journal of Nutrition 111 2106-2116. 

Bruns A, H Cypionka, J Overmann (2002) Cyclic AMP and acyl homoserine lactones increase cultivation efficiency of heterotrophic bacteria from the Central Baltic Sea. Appl Environ Microbiol 68 3978-3987. 

Capece, M. L. Lydic, R. (1997). Cyclic AMP and protein kinase A modulate... 

MacKenzie, R. S., Melan, M. A., Passey, D. K. Witt-Enderby, P. A. (2002). Dual coupling of MTi and MT2 melatonin receptors to cyclic AMP and phosphoinositide signal transduction cascades and their regulation following melatonin exposure. Biochem. Pharmacol. 63, 587-95. 

H. Kimura, Hydrogen sulfide induces cyclic AMP and modulates the NMDA receptor. Biochem. Biophys. Res. Commun. 267, 129-133 (2000). 

Argininosuccinate lyase (AL) (Fig. 40-5 reaction 4) cleaves argininosuccinate to form fumarate, which is oxidized in the tricarboxylic acid cycle, and arginine, which is hydrolyzed to urea and ornithine via hepatic arginase. Both AL and arginase are induced by starvation, dibutyryl cyclic-AMP and corticosteroids. 

Aaronica SM, Katznellenbogen BS (1993) Stimulation of estrogen receptor-mediated transcription by estrogen, cyclic-AMP and IGF-1. Mol Endocrinol 7 743... 

Table IX. Urinary Cyclic AMP and Hydroxyproline as Affected by Orthophosphate, Hexametaphosphate, and Calcium...

Figure 14.14 Quantitative biochemical similarities between the concentrations of precursors for messenger formation, the concentrations of messengers and the concentration of degradation products. These are represented by ions, cyclic AMP and a neurotransmitter. The precise concentrations of neurotransmitter in the presynaptic neurone terminal are not known if it were not localised in vesicles, it would be approximately 10 M/L so that within the vesicle it is estimated to be about 10 M/L. Similarly the precise concentration in the synaptic cleft is also a guesstimate. On the basis of the activity of exocytosis and the K , of the degradation process, it would be possible to calculate the concentration within the synaptic cleft (see Chapter 12 considerable for an example). There is Box 12.2 similarity between the substrate concentration for the zero order processes, the concentrations of messenger and the breakdown products for each process.

This enzyme [EC 4.6.1.1], also known as adenylyl cyclase and 3, 5 -cyclic AMP synthetase, catalyzes the conversion of ATP to 3, 5 -cyclic AMP and pyrophosphate. The enzyme requires pyruvate as a cofactor and will also utilize dATP as a substrate (thereby producing 3, 5 -cyclic dAMP). In the presence of NAD(P) -arginine ADP-ribosyltransferase, this enzyme is activated by covalent modification. 

In cyclic forms, such as cyclic AMP and cyclic GMP, nucleotides serve critical roles in cellular signaling mechanisms. 

De Mello WC Interaction of cyclic AMP and Ca in the control of electrical coupling in heart fibers. Biochim Biophys Acta 1986a 888 71. 

De Mello WC Cyclic AMP and junctional communication viewed through a multi-biophysical approach in Peracchia C (ed) Biophysics of Gap Junction Channels. Boca Raton, CRC Press, 1991, pp 229-239. 

TSH <1> (<1> thyroid-stimulating hormone, inhibits at a physiological concentration, inhibition is mimicked by dibuturyl cyclic AMP and forskolin, mechanism [23]) [23]... 

Several nucleotides have been detected in milk (see Table 1.9). The list includes the common mono-and dinucleotides, 3, 5 cyclic AMP, and adenosine triphosphate (ATP). The ATP is located entirely in the casein micelles (Richardson et al. 1980). Several nucleotide sugars, undoubtedly excess intermediates left over from mammary synthesis of glycoproteins, are present. Both DNA and RNA have been detected in milk (Swope and Brunner 1965 Swope et al. 1965 Langen 1967) they are probably found primarily in milk leukocytes. 

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