Adenylic acid phosphorylation

The isomerism existing between the pairs of nucleotides was attributed to the different locations of the phosphoryl residues in the carbohydrate part of the parent nucleoside,49 63 since, for instance, the isomeric adenylic acids are both hydrolyzed by acids to adenine, and by alkalis or kidney phosphatase to adenosine. Neither is identical with adenosine 5-phosphate since they are not deaminated by adenylic-acid deaminase,68 60 and are both more labile to acids than is muscle adenylic acid. An alternative explanation of the isomerism was put forward by Doherty.61 He was able, by a process of transglycosidation, to convert adenylic acids a" and 6 to benzyl D-riboside phosphates which were then hydrogenated to optically inactive ribitol phosphates. He concluded from this that both isomers are 3-phosphates and that the isomerism is due to different configurations at the anomeric position. This evidence is, however, open to the same criticism detailed above in connection with the work of Levene and coworkers. Further work has amply justified the original conclusion regarding the nature of the isomerism, since it has been found that, in all four cases, a and 6 isomers give rise to the same nucleoside on enzymic hydrolysis.62 62 63 It was therefore evident that the isomeric nucleotides are 2- and 3-phosphates, since they are demonstrably different from the known 5-phosphates. The decision as to which of the pair is the 2- and which the 3-phosphate proved to be a difficult one. The problem is complicated by the fact that the a and b" nucleotides are readily interconvertible.64,64... 

The biosynthesis of panthothenate and coenzyme A is outlined in Fig. 32 [151]. Hydroxymethylation of 172 followed by reduction and condensation with -alanine (formed by the decarboxylation of aspartate) gives pantothenic acid. Phosphorylation of panthothenate, followed by condensation with cysteine and decarboxylation gives 179. Adenylation, followed by a final phosphorylation at the ribose 3 -hydroxyl, completes the biosynthesis. 

The unambiguous chemical synthesis of adenylic acid a by phosphorylation of 3, 5 -di-0-acetyladenosine has been achieved. Subsequently, uridine 2 -phosphate was synthesized from 3, 5 -di-0-acetyluridine, and was shown to be identical with uridylic acid a. Justifiably, the "a and b designations for these isomeric nucleotides have now been abandoned, and have been replaced by the positional designations, namely, nucleoside 2 - and 3 -phosphates. 

In general, mechanisms for the biosynthesis of polyamides can be divided into three different pathways, which mainly differ in the mode of activation of the monomers (adenylation or phosphorylation), the dependency on a template, and the enzyme apparatus. In comparison to the activation by phosphorylation, adenylation involves synthesis of a phosphodiester bond between the hydroxyl group of the carboxylic group of the amino acid and the a-phosphate group of adenosine triphosphate (ATP). Activation by phosphorylation has been proposed that is, for synthesis of the tripeptide glutathione (Gly-Glu-Cys) or transpeptidase, the... 

Adenylic Acid. Muscle adenylic acid ergaden -ylic acid t -adenylic acid adenosine S -monophosphate adenosine phosphate adenosine-5 -phosphoric add edeno-sine-5. monophosphoric acid A5MP AMP NSC-20264 Addiyl Cardiomone (Na salt) Lycedan My -B-Den My-oston Phosaden. C,0HhNjO7P mol wt 347.23, C 34.59%, H 4.06%, N 20.17%, O 32,25%, P 8,92%. Nucleotide widely distributed in nature. Prepn from tissues Embden, Zimmerman, Z. Physrot Chem. 167, 137 (1927) Embden, Schmidt, ibid. 181, 130 (1929) cf. Kalckar, J. B.ol Chem. 167, 445 (1947). Prepn by hydrolysis of ATP with barium hydroxide Kerr, 3. Biot Chem. 139, 13l (1941). Synthesis Baddiley, Todd. 3. Chem. Soc. 1947, 648. Commercial prepn by enzymatic phosphorylation of adenosine. Monograph on synthesis of nucleotides G. R. Pettit. Synthetic Nucleotides vol, 1 (Van Nostrand-Reinhold. New York, 1972) 252 pp. Crystal structure Kraut, lensen, Acta Cryst 16, 79 (1963). Reviews see Adenosine Nucleic Acids. 

The different varieties of orthophosphoric monoesters and diesters which are present in all living species are exceedingly numerous. Biologically important monoesters include the mononucleotides such as, for example, adenylic acid (adenosine monophosphate, AMP), inosinic acid, vitamin Bg and many phosphorylated proteins, for example, milk caseins. Biologically important diesters include the phospholipids (e.g. lecithin and phosphatidyl inositol), plasmalogens, sphingomyelins, cyclic nucleotide monophosphates (e.g. cyclic AMP), some teichoic acids, vitamin Bj2 and of course the immensely important nucleic acids (polynucleotides) (Chapters 10 and 11). The great stability of diesters is an essential feature of the chemistry of polynucleotides. 

A reaction similar in type to that described above has been demonstrated in liver extracts by Wajzer and Baron for inosine-3 -phosphate synthesis from hypoxanthine and ribose-3-phosphate. The formation of the mononucleotide, adenylic acid, by the phosphorylation of adenosine by adenosinetriphosphate has also been described. The significance and integration of these different reactions remains a major problem for future effort. 

The phosphorylation of adenosine to adenosine-5 -phosphate was demonstrated some time ago in crude yeast extracts. The extracts did not act on guanosine, and no yeast adenylic acid was formed. More recently it has been found that the synthesis involves transfer of phosphate from ATP to adenosine, and the term adenosine phosphoki-nasc has been applied to the enzyme. The activity occurs in yeast maceration juice and in kidney and liver extracts of the rat and rabbit. The enzyme is quite specific, for a partially purified brewers yeast preparation catalyzes the phosphorylation of only two nucleosides out of seventeen which have been tested. The two nucleosides are adenosine itself and 2,6-diaminopurine riboside (2-amino adenosine). The reactions are ... 

RNA is easily hydrolyzed to mononucleotides by a weak solution of a strong base. When chromatographed on an ion-exchange resin the hydrolysate has been shown to contain two isomers, termed a and b, of each of the four mononucleotides present.Adenylic acid a is phosphorylated at C2 and adenylic acid b is phosphorylated at Enzymatic hydrolysis... 

Transfer of Phosphate from Phosphocreatine to Glucose—Here phosphocreatine is the donor of phosphate to adenylic acid forming adenosine triphosphate which passes its acid-labile phosphate over to the sugar. The adenylic acid system acts in a catalytic manner as a carrier of phosphate between phosphocreatine and glucose just as it acts catalytically in aerobic phosphorylation as a carrier of inorganic phosphate to the phosphate acceptor. If sufficiently active, adenosinetriphosphatase will interfere with the phosphorylation of the acceptor to a similar extent in both cases. 

It was first observed that adrenal homogenates and crudely fractionated particles require or can be activated by various cofactors and combinations of cofactors and metabolic intermediates, such as glucose, fumarate and other citric acid cycle components, adenosine triphosphate (ATP) or adenylic acid, nicotinamide or diphospho-pyridine nucleotide (DPN) (334,386,570,721) or triphosphopyridine nucleotide (TPN) in place of DPN plus ATP (335,786). The activity of meticulously prepared adrenal mitochondria is inhibited by low concentrations of dinitrophenol it was therefore suggested that lljS-hydroxylation requires concurrent oxidative phosphorylation (112,386). 

Meyerhof has shown that hexose phosphorylation requires Mg ions and co-zymase, which reacts with the sugar to yield hexose diphosphate and adenylic acid in a manner comparable to the action of adenine triphosphate as a phosphate carrier in muscle glycolysis. 

Phosphorylation of the terminal —CHj.OH in the ribose group produces muscle adenylic acid, from which in turn are derived adenylic phosphate and adenyl pyrophosphate (adenosine triphosphate). 

The sequence of reactions from phosphoglycerate to pyruvate is equivalent in essence to the cleavage of the phosphate group and its transfer to the adenylic acid system it is the phosphate which originally—during phosphorylation of the hexose—was supplied by ATP. The ATP invested originally is reclaimed here. 

Recently, Shimizu et al. prepared a biomimetic OPV-based bolaamphiphile (28) appending 3 -phosphorylated thymidine moieties at both ends of the rod, and complexed them with complementary 20-meric adenylic acid 29 in the aqueous solution, resulting in A-T base pairs like DNA double... 

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