Organic Chemistry

040 CHAPTER 27 Nucleosides, Nucleotides, and Nucleic Acids

If the carboxylate ion attacks the -phosphorus of ATP, an acyl pyrophosphateis

formed. The acyl phosphate then reacts with the thiol in a nucleophilic acyl substitu-

tion reaction to form the thioester.

In the third possible mechanism, the carboxylate ion attacks the -phosphorus of

ATP, forming an acyl adenylate. The acyl phosphate then reacts with the thiol in a nu-

cleophilic acyl substitution reaction to form the thioester.

In Section 17.20 we saw that carboxylic acids in biological systems can be activat-

ed by being converted into acyl phosphates, acyl pyrophosphates, and acyl adenylates.

Each of these three mechanisms puts a leaving group on the carboxylic acid that can

easily be displaced by a nucleophile. The only difference in the three mechanisms is

the particular phosphate atom that is attacked by the nucleophile and the nature of the

intermediate that is formed.

Many different nucleophiles react with ATP in biological systems. Whether nucleo-

philic attack occurs on the a-,b-,or -phosphorus in any particular reaction dependsg

a

b

O O

O

P

O−

O

P

O−

−O O

O

P

O−

adenosine

+ +

ATP an acyl pyrophosphate

AMP

O

P

O−

+ RSH ++O O−

O

P

O−

−OH+

nucleophilic attack on the -phosphorus

C

O

CH 3 O−

O

O

O−

C P

O

O

O−

P

O−

O

CH 3

O

O

O−

C P

O

O

O−

P

O−

O

CH 3

SR

C

O

CH 3

overall reaction

+ RSH + ATP + AMP ++−O

O

O−

P

O

O

O−

P

SR O− H+

C

O

O− CH 3

C

O

CH 3

ATP an acyl adenylate

nucleophilic attack on the -phosphorus

O

O−

P adenosine

+

adenosine

O− −OO +

O

O−

P

O

O

O−

P

O −O

O

O−

P

O

O

O−

P

O O−

O

O−

P

O

adenosine

O

O

O−

P

O + RSH SR ++AMP H+

C

O

CH 3

C

O

CH 3

C

O

CH 3

C

O

CH 3

overall reaction

+ RSH +++ATP SR + AMP −O

O

O−

P

O

O

O−

P

O− O− H+

C

O

CH 3

C

O

CH 3