C1.1 Enzymes and metabolism
Enzymes and metabolism explain how catalysts, active sites, reaction conditions and pathway regulation control cellular chemical reactions in living systems.
- Syllabus
- First assessment 2025
- Topic
- C1.1
- Level
- HL
Learning objectives
C1.1.1Enzymes as catalysts• Enzymes are mostly protein biological catalysts, with some RNA examples• They work in small amounts and remain unchanged after catalysisC1.1.2Role in metabolism• Metabolism is all enzyme-controlled chemical reactions in cells• Specific enzymes control which metabolic reactions occur and whenC1.1.3Anabolic and catabolic reactions• Anabolism builds complex molecules by condensation and requires energy• Catabolism breaks molecules by hydrolysis or oxidation and releases energyC1.1.4Enzymes as globular proteins• Enzymes are usually globular proteins with a small active-site pocket• The active site binds substrate, forms an ES complex, and catalyses reactionC1.1.5Induced-fit binding• Substrate binding induces shape changes in both enzyme and substrate• Induced fit aligns catalytic groups and raises substrate toward transition stateC1.1.6Molecular motion• Molecular motion brings substrates and active sites into collision• Higher kinetic energy increases successful active-site collisionsC1.1.7Relationships between structure and function• Active-site amino acid arrangement determines substrate specificity• Denaturation changes tertiary structure and active-site shape, not peptide bondsC1.1.8Effects on enzyme activity• Temperature increases rate to an optimum, then denaturation lowers activity• pH changes active-site bonding; substrate concentration rises to saturation plateauC1.1.9Measuring enzyme reactions• Measure substrate loss or product formation per unit time• Use initial rate, replicates, controls, and graphs from amylase or catalase assaysC1.1.10Effect of enzymes on activation energy• Enzymes lower activation energy by providing an alternative pathway• They stabilize transition states but do not remove the energy barrierC1.1.11(HL)—Intracellular vs. extracellular enzymes• Intracellular enzymes act in cytoplasm, organelles, or membranes• Extracellular enzymes are secreted and act outside cells, such as digestion enzymesC1.1.12(HL)—Heat generation• Exergonic metabolic reactions inevitably release some energy as heat• Endotherms use metabolic heat to maintain body temperatureC1.1.13(HL)—Cyclical and linear pathways in metabolism• Linear pathways run from substrate to product, such as glycolysis• Cyclical pathways regenerate an acceptor, such as Krebs and Calvin cyclesC1.1.14(HL)—Allosteric sites and non-competitive inhibition• Non-competitive inhibitors bind away from the active site at allosteric sites• Binding changes enzyme shape and reduces activity despite substrate presenceC1.1.15(HL)—Competitive inhibition• Competitive inhibitors resemble the substrate and bind reversibly to active sites• Increasing substrate concentration can reduce their effectC1.1.16(HL)—Feedback inhibition• End products inhibit earlier pathway enzymes when product accumulates• Feedback inhibition regulates pathway output, such as isoleucine synthesisC1.1.17(HL)—Mechanism-based inhibition• Mechanism-based inhibitors become irreversible after active-site reaction starts• Penicillin inhibits transpeptidase and prevents bacterial wall cross-linking
Enzymes Lower a Barrier; They Do Not Rewrite the Reaction
An enzyme is a biological catalyst. Most are proteins, although some RNA molecules also catalyse reactions. A small amount can act repeatedly because the enzyme emerges unchanged after products are released.
The enzyme provides an alternative pathway with lower activation energy, so more collisions can reach the transition state at the same temperature. It does not change the reactants, products or overall free-energy difference, and it does not remove the barrier completely.
A Small Active Site Runs a Reusable Catalytic Cycle
A typical enzyme is a globular protein. Folding brings particular amino-acid side chains together to form a small active-site pocket; most of the protein maintains the three-dimensional environment that makes this pocket work.
Substrate collides with and binds to the active site.
A short-lived enzyme–substrate complex forms and catalysis occurs.
Products no longer fit in the same way, so they leave; the enzyme can bind another substrate.
Induced Fit Makes Binding Catalytic
The active site is flexible, not a rigid lock. Initial contact with the correct substrate changes the conformation of both enzyme and substrate: this is induced fit.
Induced fit can:
- align catalytic groups with the bonds that must change
- strain or polarize bonds in the substrate
- stabilize the transition state
These effects lower the activation energy; complementary shape alone does not explain catalysis.
Read Enzyme-Rate Curves as Molecular Stories
| Curve feature | Molecular explanation |
|---|---|
| temperature rises toward an optimum | faster molecular motion gives more frequent energetic substrate–active-site collisions |
| temperature falls beyond the optimum | heat increasingly disrupts the enzyme's tertiary structure and active sites are lost |
| pH has an optimum range | changing H⁺ concentration alters charges and bonding that maintain active-site shape |
| substrate curve reaches a plateau | nearly all active sites are occupied; enzyme concentration now limits turnover |
An optimum is the condition giving the highest measured rate for that enzyme under that experiment. It is not a universal temperature or pH shared by all enzymes.
Initial Rate Captures the Reaction Before Conditions Drift
Reaction rate is measured as substrate disappearance or product formation per unit time. In a catalase assay, oxygen production is convenient; in an amylase assay, disappearance of starch can be timed with iodine.
Use the gradient of a tangent at the start of a product–time curve. Later rates are lower because substrate is depleted, products accumulate or conditions change, so comparing arbitrary final amounts can be misleading.
More Substrate Can Outcompete a Reversible Active-Site Inhibitor
A competitive inhibitor binds reversibly to the active site, so inhibitor and substrate cannot occupy that enzyme molecule at the same time. Raising substrate concentration increases the frequency of substrate–active-site encounters and makes substrate binding more likely.
Statins resemble part of the substrate for HMG-CoA reductase and occupy its active site. Reduced cholesterol-synthesis flux lowers LDL cholesterol; the inhibitor does not destroy the enzyme.
Allosteric Binding Changes Catalytic Capacity
An allosteric regulator binds reversibly at a specific site away from the active site. Interactions through the protein alter its conformation, stabilizing a more active or less active form.
For a non-competitive allosteric inhibitor, adding substrate cannot displace the inhibitor because the two molecules bind at different sites. Substrate may still reach an active site, but the affected enzyme's catalytic conformation has been reduced or lost.
The End Product Can Apply Its Own Reversible Brake
When end-product concentration is low, the pathway operates.
As product accumulates, it binds allosterically to an early regulatory enzyme, often the first committed step.
Pathway flux falls; when the product is used and its concentration drops, inhibition is released and production resumes.
In threonine-to-isoleucine synthesis, isoleucine inhibits threonine deaminase. This negative-feedback loop matches production to demand and avoids wasting substrates and energy.