Activated carrier molecules and their relationship to enzymes

I will focus on the meaning of ‘activated carrier molecule’ as descriptions of enzymes abound. In order to do that I need to introduce two other ideas first. I apologize to the purists for tailoring this to the level of the question.

1. Gibbs Free Energy in Biochemical Considerations

There are different ways of considering energy, and in chemistry one may be used to considering bond energy in relation to a particular molecule. However in biochemistry (which is what this question is concerned with) the focus is on the energetics of overall processes. For example “Are the reactions involved in the synthesis of glucose from pyruvate energetically favourable?" or “How can the synthesis of glucose from pyruvate occur if the overall reaction is not energetically favourable?” Likewise for individual reactions, such as the formation of peptide bonds between amino acids.

For considerations of this sort the thermodynamical concept (Gibbs) Free Energy (G) is most useful. This is because the change in free energy (ΔG) during a reaction (or other change of state) indicates whether a reaction can occur spontaneously. To quote from a useful section in Berg et al.

A reaction can occur spontaneously only if ΔG is negative.

So in the reaction sequence just mentioned, the overall synthesis of glucose from pyruvate (gluconeogenesis) has a positive ΔG and is energetically unfavourable, whereas that of the reverse process (glycolysis) is energetically favourable. And likewise peptide bond formation, not surprisingly, has a positive ΔG and is not energetically favourable.

2. How are Energetically Unfavourable Reactions Accomplished in Living Cells?

The question posed in the heading arises from the fact that gluconeogenesis and peptide bond formation occur in living cells, even though taken alone the core reactions that represent the processes are energetically unfavourable. The answer is given in the title of [section 14.1.1. of Berg et al.]

A Thermodynamically Unfavourable Reaction can be driven by a Favourable Reaction

As already stated, it is the ΔG of the overall process that is important, so if a reaction with a positive ΔG is ‘coupled‘ to one of negative ΔG of greater magnitude, the overall reaction can proceed. For example:

A → B           ΔG =  20 kJ/mol (unfavourable)
C → D           ΔG = –30 kJ/mol (favourable)
A + C → B + D   ΔG = –10 kJ/mol (favourable)

If reaction C → D proceeds alone, the free energy is liberated as biochemically useless heat. If it is coupled to reaction A → B it drives the latter with the balance being lost as heat.

3. The Role of Activated Carrier Molecules in Energy Coupling

Clearly, any coupled reaction can cause water to run uphill, as it were. But in order to continue one needs to regenerate the starting molecules for the favourable reaction. It is more efficient to specialize this regeneration process by using a limited range of specialist reactions with a negative free energy change. One description of the substrates (reacting molecules) of such specialized favourable reactions is “activated carrier molecules”. Alberts et al. define them as:

Small diffusible molecules in cells that store easily-exchangeable energy in the form of one or more energy-rich covalent bonds. Examples are ATP and NADPH.

Berg et al. also use the term, but describe it in terms of the following examples:

• ATP as an activated carrier of phosphoryl groups, because phosphoryl transfer from ATP is an exergonic process (i.e. has a negative ΔG)
• Nicotinamide adenine dinucleotide (NAD⁺) is a major electron carrier in the oxidation of fuel molecules. (Although in this case it is the half reaction involving the oxidation of the reduced form, NADH — or NADPH as mentioned by Alberts et al. — that has a negative ΔG).
• Coenzyme A… is a carrier of acyl groups (but it is the transfer of the acyl group of acyl-CoA molecules — e.g. acetyl CoA — with the generation of CoA that has a negative ΔG).

Examples of the participation of such molecules in metabolism can be found in the volume referenced, however I would emphasize that it is the specific reactions of these molecules involving the groups (or electrons) that they carry that is important.

And what about Enzymes?

As the poster stated “enzymes lower the activation energy for a reaction”. They are (generally) large proteins catalysts that have no effect on the ΔG, and they are unchanged at the end of the reaction.

Of course they are important for biochemical reactions, they participate in them, and provide binding sites to bring the substrates and activated carriers in juxtaposition so that they can react. But they couldn’t be more different from the small activated carriers.