Amines, phosphoryl transfer

Amines, phosphoryl transfer, 105-114 2-Amino-4-rerr-butylphenol, synthesis of... 

Oxidation and amination of IMP forms AMP and GMP, and subsequent phosphoryl transfer from ATP forms ADP and GDP. Further phosphoryl transfer from ATP to GDP forms GTP. ADP is converted to ATP by oxidative phosphorylation. Reduction of NDPs forms dNDPs. 

Mechanistically it was proposed that the substrate bridges both Zn(II) ions and replaces the apical amines in 28 while one of them attacks the phosphorus atom as an intramolecular nucleophile to perform the phosphoryl-transfer reaction (30). The presented observations are not re-... 

The possibility that phosphoryl transfer between amines occurs... 

Hydrolysis of Phosphates. The conclusion that phosphoryl transfer between amines is concerted does not exclude the formation of a metaphosphate intermediate in reactions with weaker nucleophiles, including water. Pyridine is a much stronger nucleophile than water and it is possible that phosphoryl transfer between pyridines is concerted because the metaphosphate ion does not have a significant lifetime in the presence of pyridine the metaphosphate ion might exist for a short time in water. However, it is much more difficult to determine whether or not the mechanism is concerted for a reaction with water than for a reaction with pyridine. 

A very clever three-phase test for the detection of metaphosphate intermediates in phosphoryl transfer reactions has been described by Rebek and coworkers (44). The basis of this test is the use of two polymers suspended in solution. The donor polymer contains a potential precursor to metaphosphate anion, e.g., an acyl phosphate or a phosphoramidate, and the recipient polymer contains an acceptor nucleophile, e.g., an amine. After reaction and physical separation of the polymers, the recipient polymer is analyzed for covalently bound phosphate. Since very few of the phosphoryl groups to be transferred will be on the surface of the donor polymer, detection of significant transfer to the recipient polymer provides evidence for a diffusible intermediate, i.e., free metaphosphate anion. Significant transfer did occur in dioxane or acetonitrile suspensions of the polymers, thereby providing evidence for an intermediate. However, this test for diffusible and, therefore, relatively stable metaphosphate anion is compromised by the choice of solvent. Both dioxane and acetonitrile can provide unshared electron pairs for the highly electrophilic metaphosphate anion such that the actual species that migrates from the donor polymer to the recipient polymer may be a complex between metaphosphate anion and the solvent. Such a role for solvent has been investigated stereochemically, the results of which will be described later in this section. 

The role of zinc ions as catalysts for phosphoryl transfer between phosphorimidazole and pyridine-2-carboxaldoxime is attributed to a lowering of the electrostatic barrier for attack of the anion of (26) on phosphorus it may also act as a template for the proper alignment of the entering and leaving groups. With amine nucleophiles it was found that zinc, in common with several bivalent cations, inhibited attack on phosphorimidazole. 

The enzymatic nucleophile is intrinsically more reactive than the ultimate acceptor. Several enzymes use the imdazole side chain of His as a transient acceptor in phosphoryl transfer reaction (Fersht, 1985). Amines react faster than alcohol with phosphoryl compounds, yet they form less stable adducts that can therefore readily allow rapid turnover. 

Probably the most important reaction involving substitution at the P atom is that of phosphorylation (phosphoryl transfer reaction), which entails nucleophilic displacement by nucleophile Y, on a phosphorus atom as in (3.89), where X is commonly OR, halogen, NR2, and so on, and Y can be water, alcohol, amines, and so on. 

Alkaline Phosphatase. Alkaline phosphatase (AP) is probably the most extensively studied phosphatase (7-9). This ubiquitous enzyme is a nonspecific phosphatase found in prokaryotes and eukaryotes. The AP reaction proceeds via an intermediate in which a serine residue (Serl02 in the Escherichia coli enzyme) is phosphorylated (mechanism b in Fig. 1). The hydrolysis of the intermediate to produce inorganic phosphate competes with phosphoryl transfer to other acceptors such as alcohols or amines, if present in solution. 

Enzymes catalyze numerous reactions including, but not limited to, oxidation, reduction, addition, elimination, phosphoryl transfer, hydrolysis, substitution, isomerization, (de)carboxylation, (de)amination, and mono- and dioxygenation (2). Cofactors such as NADP(H), FAD(H), Fe-S clusters, heme, or metal ions may be required for activity. 

Many enzymes that mediate phosphoryl transfer from ATP are thought to do so via the formation of a phosphorylated imidazole residue of histidine (Scheme 49). Spontaneous reactions of amines with ATP are legendarily slow, but now a systematic study, involving trapping of the phosphorylated amine with F , has shown that amines (pyridines, imidazoles) react with ATP 30-100-fold faster than do water or alcohols. To complicate the interpretation of the results, it was found that the rate constant for the reaction of F with ATP tetraanion is similar to rate constants for reaction of uncharged amine and oxygen nucleophiles, thus dispelling the myth that reactions of ATP and other phosphoryl anions with anionic nucleophiles are prevented by electrostatic repulsion in aqueous solution. ... 

Phosphatidylethanolamine synthesis begins with phosphorylation of ethanol-amine to form phosphoethanolamine (Figure 25.19). The next reaction involves transfer of a cytidylyl group from CTP to form CDP-ethanolamine and pyrophosphate. As always, PP, hydrolysis drives this reaction forward. A specific phosphoethanolamine transferase then links phosphoethanolamine to the diacylglycerol backbone. Biosynthesis of phosphatidylcholine is entirely analogous because animals synthesize it directly. All of the choline utilized in this pathway must be acquired from the diet. Yeast, certain bacteria, and animal livers, however, can convert phosphatidylethanolamine to phosphatidylcholine by methylation reactions involving S-adenosylmethionine (see Chapter 26). 

Full details on the phosphorylation of water and alcohols by 4-nitrophenyl dihydrogen phosphate and the NfC H ) - and N(CH3) -salts of its mono- and dianion have been published 146>. Phosphoryl group transfer from the monoanion and dianion is thought to proceed via the monomeric POf ion. Addition of the sterically unhindered amine quinuclidine to an acetonitrile solution containing the phosphate monoanion and tert-butanol produces t-butyl phosphate at a faster rate than does the addition of the more hindered diisopropylethylamine. This nucleophilic catalysis of the phosphorylation reaction is also explained by the intermediacy of the POf ion. 

A lot of biologic membrane systems and cellular organelles contain kinases, which transfer phosphate groups to proteins, especially to serine, threonine, and tyrosine residues. Self-phosphorylation of enzymes leading to acylphosphates or phosphoamides can be observed, too. With respect to their chemical stability, these phos-phoproteins are classified into acid-stable (alkali labile), hydroxyl-amine-sensitive, and acid labile. 

Group-transfer reactions (transfer of an electrophile [acyl RCOX, phosphoryl (OPOsX -), and glycosyl groups] between nucleophiles [alcohols, amines, thiols, etc.])... 

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