Throughout this book we will refer to reactions or processes for which ATP
supplies energy, and the contribution of ATP to these reactions will commonly be
indicated as in Figure 13-8a, with a single arrow showing the conversion of ATP
into ADP and Pi, or of ATP into AMP and PPi
(pyrophosphate). When written this way, these reactions of ATP appear to be
simple hydrolysis reactions in which water displaces either Pi or
PPi, and one is tempted to say that an ATP-dependent reaction is
"driven by the hydrolysis of ATP." This is not the case. ATP hydrolysis per se
usually accomplishes nothing but the liberation of heat, which cannot drive a
chemical process in an isothermal system.
Single reaction arrows such as those in Figure 13-8a almost invariably represent two-step processes (Fig. 13-8b) in which part of the ATP molecule, either a phosphoryl group or the adenylate moiety (AMP), is first transferred to a substrate molecule or to an amino acid residue in an enzyme, becoming covalently attached to and raising the free-energy content of the substrate or enzyme. In the second step, the phosphate-containing moiety transferred in the first step is displaced, generating either Pi or AMP. Thus ATP participates in the enzymecatalyzed reaction to which it contributes free energy. There is one important class of exceptions to this generalization: those processes in which noncovalent binding of ATP (or of GTP), followed by its hydrolysis to ADP and Pi, provides the energy to cycle a protein between two conformations, producing mechanical motion, as in muscle contraction or in the movement of enzymes along DNA (discussed below).
From the additivity of free-energy changes of sequential reactions, one can
see that the synthesis of any phosphorylated compound can be accomplished by
coupling it to the breakdown of another phosphorylated compound with a more
negative free energy of hydrolysis (Fig. 13-9). One can therefore describe
phosphorylated compounds as having a high or low phosphate group transfer
potential. The phosphate group transfer potential of phosphoenolpyruvate is very
high, that of ATP is high, and that of glucose-6-phosphate is low.
Single reaction arrows such as those in Figure 13-8a almost invariably represent two-step processes (Fig. 13-8b) in which part of the ATP molecule, either a phosphoryl group or the adenylate moiety (AMP), is first transferred to a substrate molecule or to an amino acid residue in an enzyme, becoming covalently attached to and raising the free-energy content of the substrate or enzyme. In the second step, the phosphate-containing moiety transferred in the first step is displaced, generating either Pi or AMP. Thus ATP participates in the enzymecatalyzed reaction to which it contributes free energy. There is one important class of exceptions to this generalization: those processes in which noncovalent binding of ATP (or of GTP), followed by its hydrolysis to ADP and Pi, provides the energy to cycle a protein between two conformations, producing mechanical motion, as in muscle contraction or in the movement of enzymes along DNA (discussed below).
| The phosphate compounds found in living organisms can be divided arbitrarily into two groups, based on their standard free energies of hydrolysis (Fig. 13-9). "High-energy" compounds have a ΔG°' of hydrolysis more negative than -25 kJ/mol; "low-energy" compounds have a less negative ΔG°' ATP, for which ΔG°' of hydrolysis is -30.5 kJ/mol (-7.3 kcal/mol), is a high-energy compound; glucose-6-phosphate, with a standard free energy of hydrolysis of -13.8 kJ/mol (-3.3 kcal/mol), is a low-energy compound. The term "high-energy phosphate bond," although long used by biochemists, is incorrect and misleading, as it wrongly suggests that the bond itself contains the energy. In fact, the breaking of chemical bonds requires an input of energy. The free energy released by hydrolysis of phosphate compounds thus does not come from the specific bond that is broken but results from the products of the reaction having a smaller free-energy content than the reactants. For simplicity, we will sometimes use the term "high-energy phosphate compound" when referring to ATP or other phosphate compounds with a large, negative, standard free energy of hydrolysis. |
| Much of catabolism is directed toward the synthesis of
high-energy phosphate compounds, but their formation is not an end in itself; it
is the means of activating a very wide variety of compounds for further chemical
transformation. The transfer of a phosphoryl group to a compound effectively
puts free energy into that compound, so that it has more free energy to give up
during subsequent metabolic transformations. We described above how the
synthesis of glucose-6-phosphate is accomplished by phosphoryl group transfer
from ATP. We shall see in the next chapter that this phosphorylation of glucose
activates or "primes" the glucose for catabolic reactions that occur in nearly
every living cell.
In some reactions that involve ATP, both of its terminal phosphate groups are
released in one piece as PPi. Simultaneously, the remainder of
the ATP molecule (adenylate) is joined to another compound, which is thereby
activated. For example, the first step in the activation of a fatty acid either
for energy-yielding oxidation (Chapter 16) or for use in the synthesis of more
complex lipids (Chapter 20) is its attachment to the carrier coenzyme A (Fig.
13-10). The direct condensation of a fatty acid with coenzyme A is endergonic,
but the formation of fatty acylCoA is made exergonic by coupling it to the net
breakdown, in two steps, of ATP. In the first step, adenylate (AMP) is transferred from ATP to the carboxyl group of the fatty acid, forming a mixed anhydride (fatty acyl adenylate) and liberating PPi. In the second step, the thiol group of coenzyme A displaces the adenylate group and forms a thioester with the fatty acid. The sum of these two reactions is the exergonic hydrolysis of ATP to AMP and PPi (ΔG°' = -32.2 kJ/mol) and the endergonic formation of fatty acyl-CoA (ΔG°' = 31.4 kJ/mol). The formation of fatty acyl-CoA is made energetically favorable by a third step, in which the PPi formed in the first step is hydrolyzed by the ubiquitous enzyme inorganic pyrophosphatase to yield 2Pi:
PPi + H2O
Thus, in the activation of a fatty acid, both of the phosphoric acid
anhydride bonds of ATP are broken. The resulting ΔG°' is the sum of the ΔG°'
values for the breakage of these bonds:
ATP + H2O
The activation of amino acids before their polymerization into proteins
(Chapter 26) is accomplished by an analogous set of reactions. An aminoacyl
adenylate is first formed from the amino acid and ATP, with the elimination of
PPi. The adenylate group is then displaced by a transfer RNA,
which is thereby joined to the amino acid. In this case, too, the
PPi formed in the first step is hydrolyzed by inorganic
pyrophosphatase. An unusual use of the cleavage of ATP to AMP and
PPi occurs in the firefly, which uses ATP as an energy source to
produce light flashesThe AMP produced in adenylate transfers is returned to the ATP cycle by the action of adenylate kinase, which catalyzes the reversible reaction
Assembly of Informational Macromolecules Requires EnergyWhen simple precursors are assembled into high molecular weight polymers with defined sequences (DNA, RNA, proteins), as described in detail in Part IV, energy is required both for the condensation of monomeric units and for the creation of ordered sequences. The precursors for DNA and RNA synthesis are nucleoside triphosphates, and polymerization is accompanied by cleavage of the phosphoric acid anhydride linkage between the α- and β-phosphates, with the release of PPi (Fig. 13-11). The moieties transferred to the growing polymer in these polymerization reactions are adenylate (AMP), guanylate (GMP), cytidylate (CMP), or uridylate (UMP) for RNA synthesis, and their deoxy analogs for DNA synthesis. We have seen that the activation of amino acids for protein synthesis involves the donation of adenylate groups from ATP, and we shall see later that the formation of peptide bonds on the ribosome is also accompanied by GTP hydrolysis (Chapter 26). In all of these cases, the exergonic breakdown of a nucleoside triphosphate is coupled to the endergonic process of synthesizing a polymer of a specific sequence.ATP Energizes Active Transport across MembranesATP can supply the energy for transporting an ion or a molecule across a membrane into another aqueous compartment where its concentration is higher. Recall from Chapter 10 that the free-energy change (ΔGt) for the transport of a nonionic solute from one compartment to another is given by
ΔGt=RT
ln(C2/C1).....................(13-4)
where C1 is the molar concentration of the solute
in the compartment from which the ion or molecule moves and
C2 is its molar concentration in the compartment into
which it moves. When a proton or other charged species moves across a membrane
without a counterion, the separation of electrical charge requires extra
electrical work beyond the osmotic work against a concentration gradient. The
extra electrical work is ZFΔψ, where Z is the (unitless) electrical charge of
the transported species, Δψ is the transmembrane electrical potential (in
volts), and F is the Faraday constant (96.48 kJ/V•mol). The total energy cost of
moving a charged species against an electrochemical gradient is
|
