Organic Chemistry

Section 27.3 Three Mechanisms for Phosphoryl Transfer Reactions 039

27.3 Three Mechanisms for Phosphoryl

Transfer Reactions

There are three possible mechanisms for a phosphoryl transfer reaction. We will illus-
trate them using the following nucleophilic acyl substitution reaction.

This reaction does not occur without ATP because the negatively charged carboxylate
ion resists nucleophilic attack and, if the tetrahedral intermediate could be formed,
the incoming nucleophile is a weaker base than the base that would have to be ex-
pelled from the tetrahedral intermediate to form the thioester. In other words, the
thiol would be expelled from the tetrahedral intermediate, reforming the carboxylate
ion (Section 17.5).
If ATP is added to the reaction mixture, the reaction occurs. The carboxylate ion at-
tacks one of the phosphate groups of ATP, breaking a phosphoanhydride bond. This
puts a leaving group on the carboxyl group that can be displaced by the thiol. There are
three possible mechanisms for the reaction of a nucleophile with ATP because each of
the three phosphorus atoms of ATP can undergo nucleophilic attack. Each mechanism
puts a different phosphate leaving group on the nucleophile.

If the carboxylate ion attacks the of ATP, an acyl phosphateis
formed. The acyl phosphate then reacts with the thiol in a nucleophilic acyl substitu-
tion reaction (Section 17.5) to form the thioester.

overall reaction

+ RSH ++ATP + ADP −O

O

O−

P

SR OH

C

O

O− CH 3

C

O

CH 3

g-phosphorus

−OO

O O

O−

P

O−

P

O

O

O

adenosine

ATP

O−

P

SR

OH

+ RSH CH 3 CC+ HO

O

CH 3 SR

C

O

CH 3 O

− O

− −

Tutorial:

Phosphoryl transfer reactions

nucleophilic attack on the -phosphorus

O ++RSH

O

O−

P

O−

C

−O

O

O−

P

OH

O

CH 3

O O

O

P

O−

O

P

O−

−O O

O

P

O−

adenosine

++

ATP an acyl phosphate

ADP

C

O

CH 3 O

−

O

O

O−

C P

O−

O

CH 3

SR

C

O

CH 3

a phosphoanhydride bond