I was wondering what exactly a coupled reaction is and why cells couple them. I read the wikipedia article as well as several others, such as life.illinois.edu but I still don't get it. Could someone explain it to me?
It's pretty simple. A reaction occurs that releases energy (like ATP losing a phosphate to become ADP + Pi). If this is uncoupled, the energy will merely turn into heat. If it is coupled, then it can be used to fuel some other process. For instance, if you couple the ATP -> ADP reaction to a certain protein, the energy can be used to modify the shape of that protein.
A coupled biochemical reaction is one where the free energy of a thermodynamically favourable reaction (such as the hydrolysis of ATP) is used to 'drive' a thermodynamically unfavourable one, by coupling or 'mechanistically joining' the two reactions.
To put it another way, two (or more) reactions may be combined by an enzyme (for example) such that a spontaneous reaction may be made 'drive' an unspontaneous one. Such reactions may be considered coupled (see, for example, Silby & Alberty (2001), quoted below).
An example is the reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase (EC 22.214.171.124; GAPDH) [see here] .
We can think of this reaction in terms of two separate reactions which are coupled mechanistically by the enzyme. (i) The NAD+ linked oxidation of an aldehyde to a carboxylic acid (the aldehyde dehydrogenase reaction) and (ii) the phosphorylation of a carboxylic acid. (Like ATP, a phosphorylated carboxylic acid may be considered a 'high energy' compound, that is one where the equilibrium for hydrolysis lies very much to the left in reaction 2 below).
Reaction 2 (Pi is inorganic phosphate).
The NAD+-linked oxidation of an aldehyde (reaction 1) is practically irreversible. That is, at equilibrium it has proceeded almost totally to the right. (As far as I am aware, this reaction has never been convincingly reversed in vitro, although I know people who have tried!) As stated above, the position of equilibrium of reaction 2 lies very much to the left.
How can one 'drive' the formation of a phosphorylated carboxylic acid by coupling it to the (spontaneous) NAD+-linked oxidation of an aldehyde?
A simplified version of the GAPDH reaction is as follows (a more complete mechanism, supported by a lot of experimental evidence, may be found in Fersht (1999), which I quote below).
Step 1. Formation on an enzyme-linked thiohemiacetal.
A sulphydryl on the enzyme (part of a Cys residue) reacts with the aldehyde group on the substrate to give a thiohemiacetal. (In the representation above, groups in brackets are all connected to a single (tetrahedral) carbon atom).
Step 2. The thiohemiacetal is oxidized by enzyme-bound NAD+ to a thiol-ester (the key step).
This (enzyme-bound) thiol-ester is a 'high energy' intermediate wherein, it may be envisaged, the free energy of aldehyde oxidation has been 'trapped'.
The final step of the GAPDH reaction is now spontaneous (proceeds to the right).
Step 3. Attack on the thiol-ester by inorganic phosphate
Thus, the free energy of NAD+-linked aldehyde oxidation has been 'sequestered' and used to 'drive' the thermodynamically unfavourable phosphorylation of a carboxylic acid, by coupling the two reactions via a ('high energy') thiol-ester.
The 'thermodynamic price' is that the GAPDH reaction (unlike NAD+-linked aldehyde oxidation) is freely reversible.
As stated above, this is a simplifed version of the GAPDH reaction. The (tetrameric) enzyme contains a tightly bound NAD+ for a start, and this needs to be taken account of. A fuller account may be found in the following reference:
For a fuller treatment of coupled biochemical reactions, see
Pyruvate kinase (EC 126.96.36.199) [see here] is another great example of a coupled biochemical reaction. In this case the reaction is almost irreversible in the direction of ATP synthesis!
The standard transformed free energy (ΔGo') for the hydrolysis of phosphoenol-pyruvate (PEP) to pyruvate and phosphate is ~ - 62 kJ/mol. This represents an equilibrium constant of about 1010 in favour of hydrolysis! (see Walsh, quoted below, pp 229-230).
For comparison, ΔGo' for ATP + H2O = ADP + Pi is about - 40 kJ/mol.
Thus the pyruvate kinase reaction may be viewed as a coupled biochemical reaction where the free energy of PEP hydrolysis is coupled to (almost irreversible) ATP synthesis.
Why does PEP have such a large negative ΔGo'? The enol form of pyruvate does not exist in appreciable quantites in aqueous solution at pH 7 (Pocker et al., 1969; Damitio et al., 1992). PEP may be considered a 'trapped' form of a thermodynamically unstable enol which is released upon hydrolysis, thus 'pulling' the equilibrium to the right. (see Walsh, quoted below, p 230, for a more thorough explanation).
Personally, I have always considered the reaction catalyzed by PK to be pretty amazing.
The above examples are instances of substrate-level coupling. But perhaps the most important coupled reaction is that which occurs in oxidative phosphorylation, ie that which occurs beween oxidation of fuels via the respiratory redox chain and synthesis of ATP via the ATP synthetase complex. In short, that which occurs in respiration.
I have 'steered clear' up to this point, as it is a very complex area and difficult to do justice to in a few lines. However, in an attempt at completeness, I'll have a go.
In the chemiosmotic theory of oxidative phosphorylation (due primarily to Peter Mitchell) electron transport via the respiratory chain to molecular oxygen creates a proton gradient across the inner mitochondrial membrane (which is normally impermeable to protons). Protons are pumped outwards. This proton gradient, or protonmotive force, may be used to 'drive' the following (thermodynamically unfavourable) reaction to the right, via the ATP synthetase complex.
This is commonly referred to as 'ATP synthesis', but what is meant is that the above reaction is maintained far from equilibrium to the right. (And this reaction, being far from equilibrium, may be used, by coupling, to 'drive' thermodynamically unfavourable processes).
That is, electron transport to oxygen is coupled to 'ATP synthesis' via a proton gradient. Among other characteristics, the coupled reactions in this case are spatially separated. (The ATP synthetase is an example of rotatory catalysis, see here).
Furthermore, the two reactions may be uncoupled.
A great example of an uncoupler is 2,4-dinitrophenol (DNP). This is a weakly acidic lipophilic compound where both the unionized (dinitrophenol) and ionized (dinitrophenolate) forms are membrane-permeable.
It may be envisaged that DNP shuttles protons across the membrane (thereby dissipating the proton gradient) by diffusing back and forth (through the membrane), picking up protons on the outside and depositing then on the inside.
Now electrons originating from foodstuffs are passed via the respiratory chain to oxygen but no ATP is synthesized: the reactions are uncoupled, and the free energy is dissipated as heat. In fact, DNP was at one time used as a slimming agent (see here), but (among other side effects) it also causes blindness.
See Abeles, Frey & Jencks (pp 620-621, quoted below), for a more thorough treatment of the mechanism of DNP.
In the analogy of a car used by nico, this uncoupled reaction is equivalent to the case where the driver has his/her foot full on the accelerator (thus burning fuel at almost the maximum rate) but where the clutch is disengaged (thus no movement or 'work' is being done). To perhaps push the analogy a bit too far, a car moving along at, say, 50 KPH is an example of a coupled energy transformation: the burning of fuel is coupled to movement.
Historically, of course, it was at one time thought that all ATP synthesis occured via substrate-level coupling. Peter Mitchell changed all that.
These topics are treated in detail in almost every textbook of biochemistry. For example, Chapter 22 (The Electron Transport Pathway and Oxidative Phosphorylation) of Abeles, Frey and Jencks (quoted below).
These two classics also deserve to be quoted.