74
chapter 5
Thermodynamics, Chemical Kinetics, and Energy Metabolism
Adenine
F IG U R E 5 -4
Structural formula of adenosine triphosphate (ATP) at pH 7.0. The three phosphate groups are identified by Greek letters
or,
p ,
and
y .
The
y -
and ^-phosphate groups are linked through phosphoanhydride bonds and their hydrolysis yields a
large negative AC“ , whereas the ex-phosphate linked by a phosphate ester bond has a much lower negative AG“ .
In vivo
most ATP is chelated to magnesium ions via two of the anionic oxygens (Mg ■
ATP2-).
tendency to approach each other to re-form ATP is min-
imized. The number of resonance forms of ADP and Pj
exceeds those present in ATP so that the products are
stabilized by a larger resonance energy. Ionization of
H
2
PO
4
^ HPC>
4
_+ H+ has a large negative A
G°'
con-
tributing the A
G°'
for ATP hydrolysis.
The free energy of hydrolysis of ATP is also affected
by Mg2+ and the physiological substrate is Mg2+ • ATP4-
(or Mg • ATP2-). The presence of magnesium ions favors
ATP hydrolysis because both ADP and Pj have higher
affinity (about six times) for Mg2+ than ATP. In vivo, the
AG
value for ATP hydrolysis is probably much higher
than A
G°'
owing to the prevailing intracellular concen-
tration of the reactants and products (in erythrocytes,
-----12.4 kcal/mol).
In some energy-consuming reactions, ATP is hy-
drolyzed to AMP and pyrophosphate, with a value of free
energy of hydrolysis comparable to that of ATP to ADP
and P;
ATP4- + H20 -* AMP2- + HP
2
0 2- + H+
A
G°' =
-7 .7 kcal/mol (-32.2 kJ/mol)
In vivo,
pyrophosphate is usually hydrolyzed to inorganic
phosphate, which also has a large negative A
G°',
HP
2
0 2- + H20 -* 2HP02- + H+
A
G°'
= -7.17 kcal/mol (-3 0 kJ/mol)
The pyrophosphate hydrolysis, although not coupled to
any particular endergonic reaction, still ensures comple-
tion of the forward reaction or process (e.g., activation of
fatty acids and amino acids, synthesis of nucleotides and
polynucleotides).
The hydrolysis of AMP to adenosine and Pj does not
yield a high negative A
G°'
because the phosphate is
linked in a normal ester bond, as opposed to the other
two linkages
(fi
and
y
), which are phosphoanhydride
bonds (Figure 5-4). The A
G°'
values of hydrolysis of other
nucleoside triphosphates (e.g., UTP, CTP, GTP) are sim-
ilar to that of ATP and they are utilized in the biosyn-
thesis of carbohydrates, lipids, and proteins (discussed
elsewhere). In addition to undergoing hydrolysis, ATP
may act as a donor of phosphoryl (e.g., in the forma-
tion of glucose
6
-phosphate; see Chapter 13), pyrophos-
phoryl (e.g., in the formation of phosphoribosylpyrophos-
phate; see Chapter 27), adenylyl (e.g., in the adenylylation
of glutamine synthetase; see Chapter 17), or adenosyl
groups (in the formation of .S'-adenosylmethionine; see
Chapter 17).
Since ATP synthesis from ADP and Pj is energy-
dependent, it requires compounds or processes that
yield larger negative A
G°'
values than ATP hydrolysis
does. Some of these compounds are organic phosphates
(Table 5-2). Other high-energy compounds are thioesters,
