Adenosine pyrophosphate

A constituent of the nucleic acid portion of nucleoproteins, and, combined, as adenosine pyrophosphate, it plays an important part in many metabolic processes. 

Glyceraldehyde-3-phosphate dehydrogenase is completely inactivated by [3-(3-bromoacetylpyridinio)-propyl]-adenosine pyrophosphate. The dihydro form, obtained by treatment with hyposulfite, does not increase the coenzyme fluorescence, nor does formation of the NADH-glyceraldehyde-3-phosphate dehydrogenase complex. If we assume that the inactivator first forms a reversible complex with the enzyme and then by formation of a covalent bond gives... 

Fig. 20. Incorporation of 14C-labeled [3-(3-bromoacetylpyridinio)-propyl]-adenosine pyrophosphate into alcohol dehydrogenase from yeast ( ) and glyceraldehyde-3-phos-phate dehydrogenase ( ).66) Abs. jUmole inactivator//r mole enzyme...

Inactivation of alcohol dehydrogenase from yeast with 14C-labeled [3-(3-bromoacetylpyridinio)-propyl]-adenosine pyrophosphate followed by oxidation showed the presence of 1-carboxymethyl histidine66. After inactivation of the enzyme with labeled [3-(4-bromoacetylpyridinio)-propyl]-adenosine pyrophosphate followed by oxidation, S-carboxymethyl cysteine was identified in the protein. In the case of glyceraldehyde-3-phosphate dehydrogenase, treatment with either coenzyme analogue leads to the modification of the cysteine residue. Treatment with [14C]nicotinamide-5-bromo-4-methylimidazole dinucleotide did not reveal any modified amino-acid-residues. The labeled nicotinamide residue split off during the recovery of the inactivated enzyme. Attempts to synthesize an inactivator labeled with a 14C-acetyl residue did not give satisfactory yields. If the enzyme-coenzyme derivative was treated with tritiated sodium boron hydride, tritium could be introduced (Fig. 22). Studies with... 

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). 

It has been reported (421) that modification with 3-(3-bromoacetyl-pyridinio) propyl adenosine pyrophosphate (Table XVI), followed by oxi-... 

Fig. 1. Preparation steps for the synthesis of [ >-(bromoacetylpyridinio)-n-alkyl] adenosine pyrophosphates.

To prepare the [m-(acetylpyridinio)-n-alkyl]adenosine pyrophosphates, 10 mmoles of acetylpyridinio-n-alkylphosphoric acid and 10 mmoles of adenosine 5 -phosphoromorpholidate (as salt of 4-morpholine iV,iV -dicyclohexylcarboxamidine) are dissolved in 20 ml of freshly distilled o-chlorophenol. The mixture is stored at room temperature for 7 days. Progress of the condensation reaction is checked daily by paper electrophoresis (0.1 M Tris chloride at pH 8.1, 30 V/cm). After the reaction is completed, 60 ml of water are added to the mixture and the suspension is extracted 3 times, each with 200 ml of ethyl ether. The first ether extract obtained is reextracted with 30 ml of water. The combined aqueous phases are reduced to a volume of 5 ml under reduced pressure and are charged on to a Dowex 1X8 column (formate form, 2 X 50 cm, 100-200 mesh). The column is washed with 6.5 liters of water, and the coenzyme analogs are eluted from the resin with a convex gradient of formic acid ... 

Fig. 2. Chromatography of [5-(3-aoetyl-l,4-dihydro-l-pyridyl)-M-pentyl]adenosine pyrophosphate on Sephadex G-10 (200 X 2 cm). The column was eluted with 60 mM glycine/NaOH buffer, pH 9.5 fractions of 4.3-ml volume were collected, and the flow rate was 13 ml/hr. The dihydrocoenzyme analog was eluted in peak 5.

In the presence of 1 mJlf ethanol, the phosphate buffer, and [4-(3-bromoacetylpyridinio) -n-butyl] adenosine pyrophosphate, inactivation and the redox reaction take place simultaneously the coenzyme analog is covalently bound partly in the reduced and partly in the oxidized form. The complex, in which the coenzyme analog is incorporated in the oxidized form, can be completely transformed into the dihydroform by treatment with sodium hyposulfite. 

ADP = adenosine pyrophosphate iCm = Michaelis constant turn. = maximum turnover number the inhibitor constants, Ki, of the unbrominated compounds are defined according to A. M. Gold and D. Fahmey [Biochcmislry 3, 783 (1964)] as K = (k-i + fcj)/fc+i and are corresponding in magnitude to dissociation constants provided that kt [Pg.257]

The inactivation of yeast alcohol dehydrogenase by carbonyl-["C] [3- (3-bromoacetylpyridinio) -n-propyl ] adenosine pyrophosphate and methylene- [ "C ] [3- (4-bromoacetylpyridinio) -n-propyl] adenosine pyrophosphate was found to be solely the result of ketoalkylation of cysteine residue 43. With horse liver alcohol dehydrogenase, cysteine-174 reacted nearly exclusively with the inactivator [3-(4-bromoacetylpyridinio)-n-propyl]adenosine pyrophosphate. Carbonyl-[ C] [4-(3-bromoacetylpyridinio )-n-butyl] adenosine pyrophosphate modifies cysteine residue... 

Acpt li)yridine-n-alkyl adenine dinu-cleotide analogs, 250 [ w-( Acetylpyridinio) - -alkyl] adenosine pyrophosphate, 252 sijectra, 254... 

Bromoacetylpyridinio-n-butyladeno-sine pyrophosphate, 257 [4 (3-Bromoacetylpyridinio) -n-butyl] -adenosine pyrophosphate, 255 (Bromoacetylpyridiniopropyl)adenosine pyrophosphate, hydrolysis rates, 254, 255... 

The enzyme purified from bull semen dephosphorylates the 5 -phosphate esters of adenosine, uridine, cytidine, guanosine, nicotinamide riboside, and the 5 -phosphate esters of deoxynucleosides, but is inactive with adenosine pyrophosphates and substrates which bear other substituents on the ribose, e.g., adenosine 2, 5 -diphosphate (124). However 5 -nucleo-tidase from potato can hydrolyze the 5 -phosphate of this diphosphate... 

The compound ad—rib—P P should be named more correctly adenosine pyrophosphate... 

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