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102 Chapter 5
5.5 Enzymatic phosphoryl transfer reactions
Phosphate esters are widespread in biological systems: phosphate mono-esters
occur as alkyl phosphates, sugar phosphates, and even phosphoproteins; whilst
phosphodiester linkages comprise the backbone of the nucleic acids RNA and
DNA, and are found in the phospholipid components of biological membranes.
Examples of phosphotriesters in biological systems are known, but they
are relatively scarce in comparison. Some examples of biologically important
phosphate esters are shown in Figure 5.27.
Phosphoryl transfer is therefore of fundamental importance to biological
systems for the biosynthesis and replication of nucleic acids, and in the transfer
of phosphate groups between small molecules and between proteins. Three
mechanisms have been observed for phosphoryl transfer reactions, as shown
in Figure 5.28. Mechanism A is a dissociative mechanism (similar to an S N 1
mechanism at carbon), in which a metaphosphate intermediate is formed, prior
to attack by a nucleophile. Mechanism B is a concerted, S N 2-like mechanism,
with no intermediate, but proceeding via a penta-co-ordinate transition state.
Mechanism C is an associative mechanism, in which attack of the nucleophile
occurs Wrst, to give a penta-co-ordinate phosphorane intermediate.
Studies of non-enzymatic phosphoryl transfer have shown that phosphate
mono-ester dianions usually react via a concerted mechanism (mechanism B),
and with hindered nucleophiles can access a more dissociative mechanism
(mechanism A). Phosphate mono-ester anions proceed via a mechanism involv-
O
O
CO −
2
phosphodiester backbone O
H 2 C O
of deoxyribonucleic acid (DNA)
O P O − O
O − O
P
− O
phosphoenolpyruvate (PEP)
O
O −
O H 2 C O P
C 17 H 35 C O CH O
H 2 C O C
O
O
NMe 3
O
− O
C 15 H 31
N
NH
N N NH 2
O
HN
O N
O
O
P
O
phosphatidylcholine - a major component
of the lipid bilayer of biological membranes
Figure 5.27 Examples of biologically important phosphates.