Organic Chemistry

Section 27.6 Other Important Nucleotides 043

lysine

arginine

NH 2

N N

N N

O

H O

H

HN C N

Mg^2 +

NH 2

+

H H

H

N+

O−

−O P

O

O

O−

P

O

O

O−

P O

OHOH

>Figure 27.2

The interactions between ATP,

and arginine and lysine

residues at the active site of an

enzyme.

Mg^2 +,

Now we can calculate the fraction of the group with 7.7 that will be in the basic form.

27.5 Kinetic Stability of ATP in the Cell

Although ATP reacts readily in enzyme-catalyzed reactions, it reacts quite slowly in
the absence of an enzyme. For example, carboxylic acid anhydrides hydrolyze in a
matter of minutes, but ATP takes several weeks to hydrolyze. The low rate of ATP hy-
drolysis is important because it allows ATP to exist in the cell until it is needed for an
enzyme-catalyzed reaction.
The negative charges on ATP are what make it relatively unreactive. These negative
charges repel the approach of nucleophiles. When ATP is bound at an active site of an
enzyme, it complexes with magnesium which decreases the overall negative
charge on ATP. (This is why ATP-requiring enzymes also require metal ions;
Section 25.5.) The other two negative charges can be stabilized by positively charged
groups such as arginine or lysine residues at the active site, as shown in Figure 27.2. In
this form, ATP is readily approached by nucleophiles, so ATP reacts rapidly in an
enzyme-catalyzed reaction, but only very slowly in the absence of the enzyme.

(Mg^2 +),

total negative charge on ATP=3.0+0.3=3.3

Ka

Ka+ 3 H+ 4

=

2.0* 10 -^8

2.0* 10 -^8 +5.0* 10 -^8

=0.3

pKa

27.6 Other Important Nucleotides

ATP is not the only biologically important nucleotide. Guanosine -triphosphate
(GTP) is used in place of ATP in some phosphoryl transfer reactions. We have also
seen in Sections 25.2 and 25.3 that dinucleotides are used as oxidizing agents (
FAD, FMN) and reducing agents (NADH, NADPH, ).
Another important nucleotide is adenosine -monophosphate, commonly known
as cyclic AMP. Cyclic AMP is called a “second messenger”because it serves as a link
between several hormones (the first messengers) and certain enzymes that regulate cel-
lular function. Secretion of certain hormones, such as adrenaline, activates adenylate
cyclase, the enzyme responsible for the synthesis of cyclic AMP from ATP. Cyclic
AMP then activates an enzyme, generally by phosphorylating it. Cyclic nucleotides are
so important in regulating cellular reactions that an entire scientific journal is devoted to
these processes.

3 ¿,5¿

NADP+, FADH 2 ,FMNH 2

NAD+,

5 ¿