Pyrophosphate derivatives

Imidodiphosphate (03P-NH-P03 ) undergoes hydrolytic decomposition forming orthophosphate and phosphoramidate, viz. 

Some measurements of the rates of this process show that it is not a simple hydroxide ion reaction, in the pH range 10-12. Determination of the acidity constants is necessary. 

The less protonated species are relatively insignificant. Crutchfield usedan expression which did not include the first term in (3) and consequently achieved best fit with different values of the rate coefficients to those reported by Goh et al. . The equilibrium constants, K, K2, for peroxodiphosphoric acid have been estimated as 2.0 and 0.3 by consideration of the corresponding values for hypo-phosphoric and pyrophosphoric acids. The values of the rate coefficients and the mechanistic interpretation of the kinetics are thus somewhat uncertain. Some data in terms of (3) has been published (Table 20). The activation energies for the overall process vary from 18.3 (pH 0) to 28 kcal.mole (pH 3). 

Effective isolation of the decomposition reaction (to oxygen) has probably not been achieved. The compound is at least 200 times more stable than peroxo-disulphate in reactions of this type .  

Reaction of peroxodiphosphoric acid with fluoride ion appears to be established. 

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Park, J. T. Uridine-5 -pyrophosphate Derivatives. II. J. biol. Chemistry... 

Figure 5.4. Schematic illustration of the cyclodextrin catalysed fission of a pyrophosphate derivative (Hennrich Cramer, 1965). 

Dilute perchloric acid or trichloroacetic acid, or ethanol, is usually employed for extraction of the glycosyl esters of nucleoside pyrophosphates from biological materials.19 The high lability of these compounds in acidic media (see Section IV, p. 356) leads to unavoidable losses during extraction with acids. Extraction with ethanol can lead to difficulties, as ethanol may not completely inactivate pyrophosphatases present in the tissue the action of these enzymes may result in partial degradation of the nucleoside pyrophosphate derivatives. Such a situation has been encountered particularly with plant tissues.20... 

The more-common 2-acetamido-2-deoxyhexoses have not been found as thymidine 5 -pyrophosphate derivatives. Nevertheless, the enzymic synthesis of thymidine 5 -(2-acetamido-2-deoxy-a-D-gluco-pyranosyl pyrophosphate) and -(2-acetamido-2-deoxy-a-D-galactopy-ranosyl pyrophosphate) has been achieved with enzyme preparations from Pseudomonas aeruginosa,116 Azotobacter vinelandii,52 and gastric mucosa.117... 

The nucleotide esters 46 and 47 are often referred to as D-ribitol 5-pyrophosphate and L-glycerol 3-pyrophosphate derivatives. 

Although no mechanistic studies of this hydrolysis have been reported, the data available suggest that the mechanism is similar to that proposed for the hydrolysis of a-D-glucopyranosyl phosphate in weakly acidic media,332 namely protonation of the glycosyl pyrophosphate derivative and slow heterolysis of the resulting monoanion (79) to produce a cyclic carbonium ion (80), a species considered to be an intermediate in the hydrolysis of glycosides (for a review, see Ref. 333). 

The hydroxyl group at C-2 of the nucleoside seems not to be significant for interaction of uridine 5 -(a-D-glucopyranosyl pyrophosphate) with liver and mung-bean epimerases, as 2 -deoxyuridine339,394 and thymidine364 derivatives are efficient substrates for these enzymes, although they are not substrates for yeast epimerase.390 The epimerase from E. coli reacts with the thymidine pyrophosphate derivative.2978... 

The evidence available is consistent with mechanism A depicted in Fig. 3. Oxidation of the a-D-glucopyranosyl pyrophosphate derivative (107a) at C-4" by NAD is followed by irreversible elimination of water from the /3-hydroxy ketone 109, with subsequent reduction of the conjugated ketone (110) by NADH. Only the NAD complexes can release the sugar nucleotide, and, consequently, the intermediates 109 and 110 are not present in free form, uncom-plexed with enzyme-NADH. 

Metal ions have been shown to catalyze the hydrolysis of phosphate esters, phosphoric and phosphonic acid halides, and various phosphoric acid anhydrides including acyl phosphates, pyrophosphate derivatives, and ATP. 

Once the polymerase binds to the promoter and strand separation occurs, initiation usually proceeds rapidly (1 -2 s). The first, or initiating, NTP, which is usually ATP or GTP, binds to the enzyme. The binding is directed by the complementary base in the DNA template strand at the start site. A second NTP binds, and initiation occurs on formation of the first phosphodiester bond by a reaction involving the 3 -hydroxyl group of the initiating NTP with the inner phosphorus atom of the second NTP. Inorganic pyrophosphate derived from the second NTP is a product of the reaction. This process is illustrated in figure 28.10. 

The structures which have been elucidated so far may be grouped into two general categories the first group possesses the 5,6-dichloro-2,6-dimethylocta-l,3,7-triene structure (61 R = Me, X = H) with additional halogen substituents in the dimethylal-lyl pyrophosphate-derived methyl carbon atoms, and the second group has the... 

The biosynthesis of the ergot alkaloids involves condensation of dimethyl-allyl pyrophosphate (derived from mevalonic acid) with tryptophan. Closure of the C- and D-rings of the alkaloid involves specific hydroxylations by cytochrome P450-dependent oxidases and rearrangements. Further modifications involve N-methylation in the presence of S-adenosyl methionine and/or condensation with amino acids and peptides. Coupling of lysergyl CoA with certain peptides forms the peptide alkaloids which are the most bioactive of the ergot alkaloids. 

JOESTEN AND JACOB r OMPA Complexes % Hydrogen Pyrophosphate Derivatives of Rare Earth Ions % Nitrogen 1 Am Cm. ohm mole ... 

Unexpected results have come to light bearing on monoterpenoid biosynthesis (Chapter 1). Banthorpe s group have shown that in the formation of the thujane and camphor skeletons, activity from labelled mevalonic acid can appear predominantly in the C5 unit supposedly derived from isopentenyl pyrophosphate and only to a minor extent in the dimethylallyl pyrophosphate-derived portion. Banthorpe has also presented evidence for a chrysanthemyl intermediate, analogous to presqualene alcohol, in the biosynthesis of artemesia ketone. 

A uridine pyrophosphate derivative of Ai -acetyl-n-glucosamine which contains an extra phosphate group has been isolated from a hot-water extract of hen oviducts. Uridine 5-phosphate and uridine 5-pyrophosphate have been recovered from acid hydrolyzates of this compound. A diphosphate ester of A-acetyl-n-glucosamine can also be obtained from acid hydrolyzates of this uridine compound. Because of the catalytic activity of phospho-A -acetyl-n-glucosamine mutase toward it, it is probably AT-ace-tyl-D-glucosamine 1,6-diphosphate. 

Rat-liver nuclei also catalyze the formation of a uridine pyrophosphate derivative of n-glucosamine from a-n-glucosamine 1-phosphate and uridine-5-triphosphoric acid. ... 

The drug most commonly used to treat Trichomonas vaginalis and some entamoebal infections, l-(2-hydroxyethyl)-2-methyl-5-nitroimidazole [Flagyl, (3)] can also produce an aversion to ethanol in patients. It has now been shown that while (3) will displace the nicotinamide moiety of NAD+ or NADP+ in the presence of pyridine transglycosidase to produce new nucleotides, there is no reaction between (3) and NADH. It is not, however, believed that the toxicity towards anaerobic organisms is due to the new adenosine pyrophosphates derived from (3). 

The first step in these reactions is probably the formation of the mixed phosphates (198), as such compounds were obtained by Hall and Kho-rana in a similar reaction conducted at 60°. It has been suggested that formation of the anhydronucleoside (199) occurs by attack of the 2-carbonyl group on C-2, with elimination of a pyro- or poly-phosphate group. An alternative mechanism may also be postulated, namely, that a cyclic pyrophosphate derivative (202, R = H or POsHa) is formed in the reaction with polyphosphoric acid, and that this then undergoes attack by the 2-carbonyl group on C-2. By a similar reaction-sequence, the 3, 5 -diphosphate of l-/3-D-arabinofuranosyluracil was prepared from uridine. ... 

The superscripts in the methods column denote the following isotopicaUy labeled nucleotide was made by this procedure nucleotide isolated as the 5 -alkyl or 5 -aryl ester only nucleotide isolated as the 2, 3 -0-isopropylidene acetal only nucleotide isolated as the 2, 3 -0-isopropylidene, 5 -alkyl or 5 -aryl ester derivative only nucleotide isolated as the 2, 3 -di-0-benzoyl, 5 -aryl ester only method involves initial formation of a pyrophosphate derivative by reaction of diphenyl phosphorochloridate with hydrobenzoin cyclic phosphate. 

This single reaction requires four coenzymes made from four different vitamins, in addition to the coenzyme lipoamide. These are thiamine pyrophosphate, derived from thiamine (Vitamin B ) FAD, derived from riboflavin (Vitamin B2) ... 

Accepting the above structures, the transfer of monosaccharide residues from nucleoside pyrophosphate derivatives to phenolic hydroxyl groups appears to result in inversion of the anomeric configuration of the glycosyl residue.i 2> This is most certainly true of the formation of aryl... 

Figure 29. Relationships h een the carbon positions in isopentenyl pyrophosphate and their sources. In the mevalonic-acid pathway, all five caibon positions in isopentenyl pyrophosphate derive from acetate and, in turn from the C-1 + C-6 and C-2 + C5 positions of glucose. In the methyierythritol-phosphate pathway, one carbon derives from the C-3 + C-4 position in glucose. Moreover, the mapping of positions from preciu ors into products of the two pathways differs sharply, as indicated by stmctures of acyclic and steroidal carbon skeletons based on the MVA (a, c) and MEP pathways (b, d).

Circular dichroism of pyrophosphate derivatives of some purine nucleosides indicates a symmetrically stacked syn conformation except when there is restricted rotation of the base. Circular dichroism has also been used to study the inhibitor action of guanosine 2 (3 )-mono-phosphate on a ribonuclease. ... 

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