714 CHAPTER 17 Carbonyl Compounds I
group breaks a phosphoanhydride bond(rather than the bond), so an intermediate
is not formed. Essentially, it is an reaction with an adenosine pyrophosphate leav-
ing group. This reaction and the ones that follow will be discussed in greater detail in
Sections 27.3 and 27.4.Acyl pyrophosphates are formed by nucleophilic attack of a carboxylate ion on the
-phosphorus of ATP.Acyl adenylates are formed by nucleophilic attack of a carboxylate ion on the
-phosphorus of ATP.Because these mixed anhydrides are negatively charged, they are not readily ap-
proached by nucleophiles. Thus, they are used only in enzyme-catalyzed reactions.
One of the functions of enzymes that catalyze biological nucleophilic acyl substitution
reactions is to neutralize the negative charges of the mixed anhydride (Section 27.5).
Another function of the enzyme is to exclude water from the site where the reaction
takes place. Otherwise hydrolysis of the mixed anhydride would compete with the de-
sired nucleophilic acyl substitution reaction.
A thioesteris an ester with a sulfur atom in place of the oxygen atom between the
acyl and alkyl groups.Thioesters are the most common forms of activated carboxylic acids in a cell.
Although thioesters hydrolyze at about the same rate as oxygen esters, they are
much more reactive than oxygen esters toward attack by nitrogen and carbon
nucleophiles. This allows a thioester to survive in the aqueous environment of the
cell—without being hydrolyzed—waiting to be a substrate in a nucleophilic acyl
substitution reaction.a thioesterHCOSR′enzyme-phosphorusO+ +an acyl adenylateROOOCO−P
−OO AdOOO−P
ROCO−P
OOAd
O−P
−OOOO−P
O−OO−P
−adenosine triphosphate pyrophosphate
ATPabSN 2p−+ +an acyl phosphateenzymeadenosine diphosphate
ADPadenosine triphosphate
ATPROOOC
ROOCO−P
O−−OOO−P
OOO−P
AdOO−P
−O OOO−P
OOO−P
Ad-phosphorusOOO−P
ROOOCO−P
O−−OOO−P
AdOO−P
−O OOO−P
OOO−P
RO AdOC
−+ +an acyl pyrophosphate adenosine monophosphate
AMPadenosine triphosphate
ATP-phosphorusenzyme