Enzymes (A-level only) — AQA A-Level Chemistry
Test yourself on Enzymes (A-level only) with AQA A-Level practice questions.
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Enzymes (A-level only) explained
An enzyme is a protein, a chain of amino acids joined by peptide links, folded into a compact globular shape with its polar R groups mostly on the outside so it dissolves in water.
Read the full explanation
Its catalytic power comes entirely from that fold: the tertiary structure creates a small cleft, the active site, whose shape and charge distribution are complementary to one particular substrate. Anything that disturbs the fold destroys the function. Heating or a large change in pH breaks the hydrogen bonds and ionic attractions between R groups, the chain unravels, the active site loses its shape and the enzyme is denatured, even though every peptide link and therefore the whole primary structure is still intact.
The action of enzymes as catalysts, including the concept of a stereospecific active site that binds to a substrate molecule.
The active site is a small cleft in the folded protein whose shape and pattern of charges are complementary to one particular substrate. The substrate binds there, forming an enzyme-substrate complex, and is held in exactly the orientation the reaction needs, with the bonds that must break already strained. That gives the reaction an alternative route with a lower activation energy, so at any given temperature a far larger fraction of collisions has enough energy to react and the rate rises sharply. The enzyme is unchanged at the end and immediately binds another substrate molecule. Because the amino acids that form the site are themselves chiral, the site is chiral, so it fits only one enantiomer of a substrate.
The principle of a drug acting as an enzyme inhibitor by blocking the active site.
A competitive inhibitor is a molecule similar enough in shape to the substrate to enter the active site, but which either does not react once there or binds much more tightly than the substrate does. While it sits in the site, substrate molecules cannot bind, so fewer enzyme-substrate complexes form and the rate of the catalysed reaction falls. If the binding is reversible, raising the substrate concentration wins the competition back; if it is irreversible, that enzyme molecule is out of action permanently. Many drugs work this way, and the value of one depends on selectivity: a useful antibacterial blocks an enzyme the bacterium needs to survive and that human cells either do not have or do not depend on.
Computers can be used to help design such drugs.
Designing an inhibitor by trial and error means synthesising and testing thousands of compounds, which is slow and expensive. Computer modelling shortens the search. The three-dimensional structure of the enzyme is first determined, usually by X-ray crystallography, and software then maps the active site: its shape, the positions of the charged and polar groups and the places where hydrogen bonds could form. Candidate molecules are docked into that model on screen and scored for how well they fit and how strongly they would bind, so only the most promising few are actually made and tested in the laboratory. The model must be built for the correct enantiomer, since only one hand of the molecule will fit.
Students should be able to: explain why a stereospecific active site can only bond to one enantiomeric form of a substrate or drug.
Enantiomers are non-superimposable mirror images, which arise when a carbon atom carries four different groups. They have identical bonds and identical bond angles, so they differ only in the arrangement in space, like a left and a right hand. The active site of an enzyme is built from amino acids, which are themselves chiral, so the site has a definite handedness too. A substrate binds only when several groups meet matching points in the site at the same time, and a mirror image cannot bring all of them into position at once: line up two and the third points the wrong way. So one enantiomer binds and reacts and the other does not, which is why a racemic drug is at best half active.
Your focus
- State what an enzyme is made of and which level of protein structure creates its active site.
- Explain what happens to an enzyme when it is heated strongly, in terms of the bonds broken.
- Explain why a denatured enzyme no longer works even though its primary structure is unchanged.
Show all 15 objectives
- Explain how forming an enzyme-substrate complex speeds a reaction up, naming the alternative route of lower activation energy rather than a lowering of the original route's activation energy.
- Explain what 'stereospecific active site' means and what follows from it for a pair of optical isomers.
- State two properties of a catalyst and show that an enzyme has both of them.
- Explain why an inhibitor that occupies the active site stops the enzyme working, even though the inhibitor is not itself changed by the enzyme.
- State the structural requirement an inhibitor must meet and explain why it is necessary.
- Suggest why a drug that inhibits a bacterial enzyme may be safe for the patient.
- Describe how a computer model of an active site is used to identify possible drug molecules.
- Explain two advantages of modelling a drug before synthesising it.
- State why the model must take account of the chirality of the candidate molecule.
- Explain what makes a molecule chiral and identify a chiral carbon in a given structure.
- Judge the claim that enzymes work equally well on both optical isomers of a substrate, and give the reason it is false in terms of the shape of the active site.
- Deduce the consequence for the effectiveness of a drug supplied as a racemic mixture.
Enzymes (A-level only) exam tips
Marking Points
- one mark for an enzyme described as a protein, a chain of amino acids joined by peptide links
- one mark for the tertiary structure creating the active site
- one mark for denaturing described as loss of the three-dimensional shape of the active site
- one mark for stating that hydrogen bonds and ionic attractions are broken while the peptide links survive
- one mark for the active site having a shape complementary to the substrate
- one mark for the substrate binding to give an enzyme-substrate complex
- one mark for catalysis described as providing an alternative route of lower activation energy
- one mark for the enzyme being unchanged at the end so it can act again
- one mark for the inhibitor having a shape similar to the substrate so it fits the active site
- one mark for the active site being blocked so the substrate cannot bind
- one mark for the rate of the catalysed reaction being reduced as a result
- one mark for selectivity, that a useful drug blocks an enzyme needed by the pathogen and not by the patient
- one mark for the model being built from the known three-dimensional structure of the enzyme's active site
- one mark for candidate molecules being tested for fit on the computer before they are synthesised
- one mark for naming an interaction the model predicts, such as hydrogen bonding to groups in the site
- one mark for the benefit, that fewer compounds have to be made and tested so cost and time fall
- one mark for enantiomers defined as non-superimposable mirror images arising from a carbon with four different groups
- one mark for the active site itself being chiral because it is built from chiral amino acids
- one mark for only one enantiomer being able to align its groups with the binding points of the site
- one mark for the consequence, that the other enantiomer is not catalysed or is inactive as a drug
Examiner Tips
- 💡If the question is about denaturing, name the bonds that break and the bonds that do not; that contrast is where the marks sit.
- 💡The tertiary structure is the answer to almost every 'why does the active site work' question.
- 💡The phrase examiners want is 'alternative route of lower activation energy'; write it out in full.
- 💡Remember the stereochemical point: an enzyme does not work equally well on both optical isomers of its substrate.
- 💡Answer in three steps: similar shape, site blocked, rate falls. Missing the first step loses the explanation mark.
- 💡If the question mentions a drug, add the selectivity point; that is usually the fourth mark.
- 💡Frame the answer around the active site: the computer models the site, then tests molecules against it.
- 💡A benefit mark needs a comparison, so say 'fewer compounds need to be synthesised' rather than 'it is better'.
- 💡Use the word 'non-superimposable'; 'different shape' on its own is not enough for the definition mark.
- 💡Say why the mismatch matters: three or more points of contact have to line up at once, and a mirror image cannot manage it.
Common Mistakes
- saying that heat breaks the peptide links of an enzyme
- claiming a denatured enzyme has a different primary structure
- describing enzymes as inorganic catalysts like the transition metals
- saying the enzyme is used up during the reaction it catalyses
- saying a catalyst lowers the activation energy of the original route rather than offering a different one
- claiming the enzyme shifts the position of the equilibrium as well as speeding the reaction up
- describing the substrate as permanently bonded into the active site
- saying the active site accepts any molecule of roughly the right size
- saying the inhibitor destroys or denatures the enzyme rather than occupying its site
- saying the drug binds to the substrate instead of to the enzyme
- omitting the requirement that the inhibitor must resemble the substrate in shape
- assuming any large molecule will act as an inhibitor
- saying the computer manufactures the drug
- claiming computer design removes the need for laboratory and clinical testing
- ignoring that only one enantiomer of the candidate will fit the site
- describing the model as predicting the percentage yield of the synthesis
- saying the two enantiomers have different bond lengths or bond angles
- claiming enantiomers have different molecular formulae
- saying both enantiomers fit but react at different rates, with no reason given
- forgetting that half of a racemic mixture is the form that does not work