Thermodynamics of Bioreactions
101
several orders of magnitude across the membranes that separate organelles, and the actual AG may
therefore be much different from AG°. This also holds for most other biochemical reactions, and
one must be extremely careful when evaluating thermodynamic feasibility based exclusively on the
AG“ for the reaction. This is further illustrated in Example 4.3.
From the calculated free energy changes (see Table 4.2) it is observed that, except for the hexokinase-
phosphofructokinase-, pyruvate kinase*, and, possibly, the triose-P*isomerase-catalyzed reactions, all the
reactions of the EMP pathway are close to equilibrium (the free energy change for the reaction series 3-
P-glyceraldehyde dehydrogenase and 3-phosphoglycerate kinase is also close to zero). Thus, the
in vivo
activity of several of the enzymes is sufficiently high to equilibrate the conversions, or, in other words,
the forward and backward reactions of these conversions are much faster than the net flux through the
pathway. Obviously, these equilibrium reactions are very sensitive to changes in the concentration of
pathway intermediates, and therefore they rapidly communicate changes in flux generated by one of the
reactions with a high negative free energy change throughout the rest of the pathway.
The three reactions with large negative free energies are
thermodynamically irreversible
and are often
considered as key control points in the pathway. Obviously, the
in vivo
activity of the three enzymes
hexokinase, phosphofructokinase, and pyruvate kinase is too low to equilibrate the reactions they
catalyze. This may be the result of either too low gene expression,
i.e.,
the
in vivo rmUL
of the enzymes is
too low, or regulation at the enzyme level,
e.g.,
allosteric regulation or covalent enzyme modifications.
With the large and negative free energies of hexokinase and pyruvate kinase the first and last reaction of
the pathway may be thermodynamically favored even when the glucose concentration becomes very low
and even when the pyruvate concentration increases. Thus, the pathway is designed to operate for a wide
Table 4,2 Free energy changes over reactions of the EMP pathway in the human erythrocyte
Reaction
AG°
AG
AG
fkJ mol'1)
8
8
U
1
(kJ mol'1)
Hexokinase
-16.74
[glc\ atp]
-33.3
Glucose*6-P isomerase
1.67
A
G° + RT
In
6i?J
[G6P]
-2.7
Phosphofructokinase
-14.22
m
- +r t ^
dp}adp}
[F6PIa TP]
-18.7
Aldolase
23.97
A(? +XTJ
[.
FDP
]
AG° + /;n n ]I a4P l1
[d h a p ]
0.7
T riose-P-isomerase
7.66
2.7
Phosphoglycerate mutase
4.44
A G ^ R r i n f ^ ]
[3
p g ]
1.0
Enolase
1.84
AGfl + /m n (£ ^ ]
[2
PG]
1.2
Pyruvate kinase
-31.38
AG°+RTinlPrR]ATP\
[pep\ a d p]
-23.0
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