Adenosine 5-phospho

N—O-sulfation of minoxidil in the presence of adenosine-3 -phospho-5 -phosphosulfate (PAPS) (equation 24). The enzyme-synthetized product was identical to authentic N—O-sulfate with respect to chromatographic behavior and mass spectral characteristics and was split to minoxidil when treated with sulfatase183. The pH optimum for minoxidil N—O-sulfation was about 8.0. Enzyme activity in crude preparations was maintained for several months during storage at —76°C, while activity of partially purified enzyme was lost under these conditions183. 

It has been shown that inversion of the configuration at C-5 of D-glucuronic acid, to give L-iduronic acid, occurs at the polymer level in the biosynthesis of dermatan sulphate and is promoted by the presence of adenosine phospho-phosphoryl sulphate. Inversion of the configuration at isolated sites can take place in the absence of sulphated hexosamines, but the formation of repeating blocks containing L-iduronic acid residues is associated with the sulphation of adjacent hexosamine residues at 0-4. 

The major relaxing transmitters are those that elevate the cAMP or cGMP concentration (Fig. 3). Adenosine stimulates the activity of cAMP kinase. The next step is not clear, but evidence has been accumulated that cAMP kinase decreases the calcium sensitivity of the contractile machinery. In vitro, cAMP kinase phosphorylated MLCK and decreased thereby the affinity of MLCK for calcium-calmodulin. However, this regulation does not occur in intact smooth muscle. Possible other substrate candidates for cAMP kinase are the heat stable protein HSP 20, (A heat stable protein of 20 kDa that is phosphorylated by cGMP kinase. It has been postulated that phospho-HSP 20 interferes with the interaction between actin and myosin allowing thereby smooth muscle relaxation without dephosphorylation of the rMLC.) Rho A and MLCP that are phosphorylated also by cGMP kinase I (Fig. 3). 

Figure 24-8. Biosynthesis of sphingomyelin (A), galactosylceramide and its sulfo derivative (B). (PAPS, "active sulfate," adenosine 3 -phosphate-5 -phospho-sulfate.)...

Dl-iike receptors activate the Gs transduction pathway, stimulating the production of adenylyl cyclase, which increases the formation of cyclic adenosine monophosphate (cAMP) and ultimately increases the activity of cAMP-dependent protein kinase (PKA). PKA activates DARPP-32 (dopamine and cyclic adenosine 3, 5 -monophosphate-regulated phosphoprotein, 32 kDa) via phosphorylation, permitting phospho-DARPP-32 to then inhibit protein phosphatase-1 (PP-1). The downstream effect of decreased PP-1 activity is an increase in the phosphorylation states of assorted downstream effector proteins regulating neurotransmitter... 

L-cysteine. The process is completed by glucosylation and addition of S03 at the nitrogen (Equation 10) by reaction with 3 -phospho-adenosine-5 -phosphosulfate. 

Phosphoribosylpyrophosphate (PRPP) synthetase is one of the very few enzymes which transfer a pyrophosphoryl group from ATP in one step. When the synthesis is carried out in lsO-enriched water, lsO is incorporated into the PRPP, but not into AMP.91 The lsO in the PRPP arises from a pre-exchange between the H2180 and the ribose phosphate, and hence the results confirm that fission of the /5-P—O bond takes place. PRPP and ATP are starting materials in the biosynthesis of histidine, and Ai-(5 -phospho-D-ribosyl)adenosine triphosphate (29) is an intermediate. The... 

Additional information <3, 11> (<3> N-acetyl-L-glutamate and L-glutamine have no influence on activity [3] <11,13> not inhibitory adenosine-5 -tri-phospho(5 )adenosine, phosphate, phosphonoformate [14]) [3, 14]... 

Fig. 1. Structure of CoA, composed of three parts a nucleotide pan derived from 3 -adenosine-5 -pbosphate, forming a phosphodiester bond with a 4-phospho derivative of pantothenic acid, and a third pan derived horn the amino acid, cysteine. The side chain SH group of the latter is ftee in this compound and is readily acylated, and thus able to act as a carrier for acyl groups in biochemical reactions in which it transfers that group between two substrates...

The hydrolysis of adenosine 3. 5 -cyclic monophosphate (cAMP) by the cobalt complexes (215) was considered here earlier,187 as was the Ce(IV)-catalysed hydrolysis of phospho monoesters in nucleotides.189 A review (ca 100 references) on current data on the mechanism of cleavage-transesterification of RNA has appeared.258 In this review special attention was focused on the two crucial steps in the hydrolysis of RNA, i.e. cleavage-transesterification and hydrolysis of the cyclic phosphodiester (Scheme 14). The catalysis of various amines for the hydrolysis of RNA has been looked at and ethylenediamine and propane-1,3-diamine are highly active under physiological conditions because they exist as the catalytically active monocation forms.259... 

Fan G, Shumay E, Malbon CC, Wang H (2001) c-Src tyrosine kinase binds the beta 2-adrenergic receptor via phospho-Tyr-350, phosphorylates G-protein-linked receptor kinase 2, and mediates agonist-induced receptor desensitization. J Biol Chem 276(16) 13240-13247 Ferguson G, Watterson KR, Palmer TM (2000) Subtype-specific kinetics of inhibitory adenosine receptor internalization are determined by sensitivity to phosphorylation by G protein coupled receptor kinases. Mol Pharmacol 57(3) 546-552... 

Kinases and sulfotransferases utilize similar substrates and catalyze similar reactions. Both transfer anionic groups (Scheme 14.9). Both enzyme classes are capable of binding adenosine-based substrates. Sulfotransferases bind 3 -phospho-adenosine-5 -phosphosulfate (PAPS) (35) as a sulfate donor and kinases bind adenosine-5 -triphosphate (ATP) (36) as a phosphoryl donor. 

Inosine 5-phosphate (XXX) was converted to adenylosuccinate [6-(succinylamino)-9-(5-0-phospho-/8-D-ribofuranosyl)purine, XXXI] which was isolated by ion-exchange chromatography and was identified by analysis and by its characteristic absorption spectrum. The stoichiometry of the reaction was also verified by isolation and determination of the reactants. Hydroxylamine could replace L-aspartate, and the product formed was isolated and tentatively identified as iV -hydroxyadenosine 5-phosphate. A crude extract of Escherichia coli B was shown to split adenylosuccinate to adenosine 5-phosphate and fumaric acid. 

The biochemical pathway of both assimilatory and dissimilatory sulfate reduction is illustrated in Figure 1. The details of the dissimilatory reduction pathway are useful for understanding the origin of bacterial stable isotopic fractionations. The overall pathways require the transfer of eight electrons, and proceed through a number of intermediate steps. The reduction of sulfate requires activation by ATP (adenosine triphosphate) to form adenosine phosphosulfate (APS). The enzyme ATP sulfurylase catalyzes this reaction. In dissimilatory reduction, the sulfate moiety of APS is reduced to sulfite (SO3 ) by the enzyme APS reductase, whereas in assimilatory reduction APS is further phosphorylated to phospho-adenosine phosphosulfate (PAPS) before reduction to the oxidation state of sulfite and sulfide. Although the reduction reactions occur in the cell s cytoplasm (i.e., the sulfate enters the cell), the electron transport chain for dissimilatory sulfate reduction occurs in proteins that are peiiplasmic (within the bacterial cell wall). The enzyme hydrogenase... 

In modern organisms operating under oxic conditions this is more difficult, because sulfur arrives as sulfate and this has to be bound and reduced so that the sulfur can be utilized biologically (see Figure 10). Initially sulfate can be bound to ATP (adenosine trisphosphate) as APS (phospho-adenosine monophosphate sulfate). 

Phospho-adenosine monophosphate sulfate (APS) PAPS has an additional 3 -phosphate... 

Muscle Adenylic Acid (5-Phospho-adenosine). Embden discovered in muscle extracts an adenylic acid which has since been isolated from heart muscle and from the brain. Since it was already known that an... 

Jachimowicz claimed to have synthesized 5-phosphoadenosine (in poor yield) by direct phosphorylation of adenosine with phosphorus oxychloride in pyridine, but Bredereck showed that a mixture of phosphoric esters of adenosine actually results, as might have been anticipated. Levene and Tipson succeeded in synthesizing 5-phospho-adenosine (in poor yield) by phosphorylation of 2,3-diacetyl-adenosine to give AT-phos-pho 5-phospho-2,3-diacetyl-adenosine, followed by deacetylation by alkali, and removal by acid-hydrolysis of the labile phospho group attached to nitrogen. (This synthesis was confirmed by Bredereck, et al. ) In a similar manner they phosphorylated 2,3-isopropylidene-adenosine to iV,5-di-phospho-2,3-isopropylidene-adenosine from which the acid-labile iV-phospho and isopropylidene groups were hydrolyzed, giving 5-phospho-adenosine. 

Phospho-adenosine enters into the structure of cozyftiase, and plays a very important part in phosphate transfer in muscle and in alcoholic fermentation by yeast. 

Synthetic 3-phospho-adenosine, identical with that from ribosenucleic acid, has been prepared by direct phosphorylation of adenosine with phosphorus oxychloride in the presence of barium hydroxide, but this method of synthesis affords no confirmation of the above formulation. 

Gulland and Jackson performed some experiments with 5-nucleotidase, a highly specific enzyme which dephosphorylates 5-phospho-adenosine and -inosine but not" 5-phospho-guanosine and -uridine it is apparently not yet known whether the enzyme dephosphorylates 5-phos-pho-cytidine. They found that a mixture of phosphodiesterase with 5-nucleotidase liberates 35% of the total phosphorus as inorganic phosphate, and therefore decided that two or more of the phosphoryl groups may be attached at position (5) of the ribose units. The 35% dephosphorylation, intermediate between 25 and 50%, was explained as the result of simultaneous, competitive diesterase action at A and B, on two or more phosphoryl groups ... 

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