Enzymes
Enzymes are biological catalysts — almost always globular proteins — that speed up metabolic reactions by lowering activation energy without being consumed. The PMDC MDCAT 2026 syllabus asks for four things: the distinguishing characteristics of enzymes, the mechanism of enzyme action, the effects of temperature, pH and concentration, and enzyme inhibitors. Expect 2–4 MCQs from this chapter.
Nature and Mechanism of Enzyme Action
An enzyme provides an alternative reaction route with a lower energy barrier. It does not supply energy, does not change the free energy difference between reactants and products, and does not shift the position of equilibrium — it only lets the system reach that equilibrium sooner.
The minimum energy colliding molecules must possess to react. Enzymes lower Ea by binding and stabilising the strained transition state, so a far larger fraction of collisions becomes productive.
A small pocket built from just a few amino acid residues. Those residues may sit far apart in the primary sequence but are brought together by the tertiary folding of the protein — which is exactly why denaturation destroys activity.
Lock-and-key vs induced fit
| Feature | Lock and key (Fischer, 1894) | Induced fit (Koshland, 1958) |
|---|---|---|
| Active site | Rigid, pre-formed shape | Flexible, moulds around substrate |
| Substrate | Must match exactly | Induces the final shape on binding |
| Explains | Basic specificity | Specificity and allosteric regulation |
| Status | Historical, simplified | Currently accepted model |
Factors Affecting Enzyme Activity
Temperature
Below the optimum, each 10 °C rise roughly doubles the rate (more frequent, more energetic collisions). Above the optimum, hydrogen and ionic bonds break, the active site loses shape and the enzyme is denatured — normally irreversibly. Human enzymes peak near 37 °C; thermophilic bacterial enzymes work near 80 °C because extra ionic bonds, disulphide bridges and a tightly packed hydrophobic core resist thermal disruption.
pH
Each enzyme has a narrow optimum. Moving away from it alters the ionisation of acidic and basic R groups, disturbing the ionic bonds that hold the active site in shape; the effect is reversible for moderate shifts and irreversible at extremes.
| Enzyme | Site of action | Optimum pH |
|---|---|---|
| Pepsin | Stomach | ~2.0 |
| Salivary amylase | Mouth | ~6.8 |
| Trypsin | Small intestine | ~8.0 |
| Arginase | Liver | ~10.0 |
Substrate and enzyme concentration
With enzyme fixed, raising substrate increases the rate until every active site is occupied; the curve then plateaus at the maximum rate, because every active site is already busy. Once saturated, the only way to go faster is to add more enzyme — so with excess substrate the rate is directly proportional to enzyme concentration.
Enzyme Inhibition
| Feature | Competitive | Non-competitive |
|---|---|---|
| Binding site | Active site | A site elsewhere on the enzyme |
| Resembles substrate? | Yes | No |
| Effect of adding more substrate | Inhibition is overcome | Inhibition is not overcome |
| Effect on the enzyme | Blocks the active site while it is bound | Distorts the shape of the active site |
| Maximum rate still reachable? | Yes — with enough substrate | No — the ceiling is lowered |
| Example | Malonate on succinate dehydrogenase | Cyanide on cytochrome oxidase |
Irreversible inhibitors form covalent bonds and cannot be displaced by substrate or dilution — for example organophosphates on acetylcholinesterase. Heavy metal ions (Hg2+, Ag+, Pb2+) bind –SH groups of cysteine and denature the protein.
Allosteric and end-product inhibitors
An inhibitor binds a regulatory (allosteric) site distinct from the active site, changing the conformation of the whole molecule so that the active site no longer fits the substrate. This is the structural basis of non-competitive inhibition — which is why extra substrate cannot reverse it.
The final product of a metabolic pathway inhibits an earlier enzyme — usually the first — preventing wasteful over-production. Phosphofructokinase inhibited by ATP is the standard example: glycolysis slows when the cell is already energy-rich.
Cofactors and Coenzymes
Many enzymes are inactive on their own. The protein part is the apoenzyme; apoenzyme + cofactor = the active holoenzyme.
- Coenzyme
- Organic, loosely and reversibly bound; often vitamin-derived. NAD (from niacin), FAD (from riboflavin), coenzyme A (from pantothenic acid).
- Prosthetic group
- Organic but firmly and permanently attached — for example the iron-containing haem of catalase.
- Activator / metal ion
- Inorganic ion required for activity: Zn2+ in carbonic anhydrase, Mg2+ for kinases, Cl− for salivary amylase.
This is why a deficiency of B-group vitamins cripples many pathways at once: the vitamins are precursors of the coenzymes that dehydrogenases and transferases depend on.
Worked MCQs
Five MCQs covering the high-yield testing patterns for enzymes. Read every explanation carefully.
Q1. A competitive inhibitor slows an enzyme because it:
A competitive inhibitor is a structural mimic of the substrate, so the two compete for the same active site. Adding excess substrate therefore out-competes the inhibitor and full activity returns. Binding at a separate site and distorting the active site is non-competitive inhibition, which extra substrate cannot reverse.
Q2. Cooling an enzyme to 5 °C reduces its activity because:
Low temperature only slows molecular movement; the tertiary structure is intact and activity returns completely on warming. Denaturation — the irreversible loss of active-site shape — is caused by high temperature, not cold. This is one of the most frequently set traps in the chapter.
Q3. An enzyme cannot drive a thermodynamically unfavourable reaction because it does not alter the:
A catalyst lowers the energy barrier for both directions by the same amount, so it accelerates the approach to equilibrium without moving it. The free energy difference between reactants and products is fixed by their chemistry, not by the catalyst.
Q4. The coenzyme NAD is derived from which vitamin?
NAD comes from niacin and FAD from riboflavin — the pair most often confused in the exam. Coenzyme A comes from pantothenic acid (B5). A niacin deficiency therefore impairs every dehydrogenase that needs NAD.
Q5. Pepsin has an optimum pH of about 2. At pH 8 its activity is lost because:
pH determines how the acidic and basic R groups of the protein are ionised. Shifting far from the optimum breaks the ionic bonds that hold the active site in its precise shape, so the substrate no longer fits. Moderate shifts are reversible; extreme ones denature the enzyme outright.
Quick Recap
- Enzymes lower activation energy; they never change ΔG or the position of equilibrium.
- Active site = a few residues brought together by tertiary folding → denaturation destroys it.
- Fischer = lock and key (rigid); Koshland = induced fit (flexible, accepted).
- +10 °C roughly doubles the rate below the optimum; above it, denaturation. Cold slows but does not denature.
- Optimum pH: pepsin ~2, salivary amylase ~6.8, trypsin ~8.
- Raising substrate speeds the reaction until every active site is busy; after that only more enzyme helps.
- Competitive inhibitor → binds the active site, resembles the substrate, overcome by excess substrate. Non-competitive → binds elsewhere, distorts the active site, not overcome.
- Apoenzyme + cofactor = holoenzyme. Coenzyme = loose (NAD, FAD, CoA); prosthetic group = permanent (haem).
- Allosteric inhibitors bind a regulatory site away from the active site; feedback inhibition is by the end product of the pathway (ATP on phosphofructokinase).