AP Biology 3.1-3.2: Enzymes

Enzyme

An enzyme is a biological catalyst, usually a protein, that accelerates a reaction without being consumed. Most metabolic reactions require enzyme catalysis to proceed at biologically useful rates.

What is the role of a catalyst in a chemical reaction?

A catalyst provides an alternative reaction pathway with a lower activation energy, $E_a$. It increases reaction rate but is regenerated and does not undergo permanent chemical change.

How do enzymes affect activation energy and reaction free energy?

Enzymes lower the activation energy, $E_a$, needed to reach the transition state, but they do not change the overall reaction free energy, $\Delta G$. Therefore, they do not change whether a reaction is exergonic or endergonic.

How does an enzyme affect the equilibrium position of a reversible reaction?

An enzyme speeds up both the forward and reverse reactions by lowering their activation energies. It does not change the equilibrium constant, $K$, or the equilibrium composition.

Substrate

A substrate is a reactant molecule that binds to an enzyme and is chemically converted into product(s).

Active site

The active site is the region of an enzyme where substrate binding and catalysis occur. Its three-dimensional shape and chemical properties arise from specific amino acid residues.

Why are enzymes highly specific for particular substrates?

The active site has a specific three-dimensional shape and arrangement of functional groups, charges, polarities, and hydrophobic regions. These features favor binding and reaction with particular substrate(s) and transition-state structures.

Induced-fit model

The induced-fit model states that substrate binding causes a small conformational change in the enzyme. This change produces a better fit with the substrate and transition state, improving catalysis.

How does the induced-fit model improve on the lock-and-key model?

The lock-and-key model treats the enzyme and substrate as rigid structures that fit immediately. Induced fit recognizes that both binding partners can change conformation, allowing the enzyme to optimize transition-state stabilization.

Enzyme-substrate complex

The enzyme-substrate complex is the temporary association formed when a substrate binds to an enzyme's active site. Within this complex, the substrate is positioned and chemically activated for reaction.

How can an enzyme lower the activation energy by bringing reactants together?

For reactions involving multiple substrates, the enzyme binds them close together and in the correct orientation. This increases the likelihood of productive collisions and reduces the energetic difficulty of forming new bonds.

How can an enzyme's active site provide a favorable reaction environment?

A particular arrangement of amino acid side chains can create a local environment with suitable polarity, charge, acidity, or hydrophobicity. This environment can stabilize developing charges and promote the desired reaction.

How can enzymes promote bond breaking and formation through substrate distortion?

An enzyme can strain or contort a bound substrate toward its transition-state geometry. This makes existing bonds easier to break and new bonds easier to form, lowering $E_a$.

Can an enzyme temporarily participate in the chemical reaction itself?

Yes. An amino acid side chain or other catalytic group may form a temporary covalent bond with the substrate or transfer ions or chemical groups. The enzyme is regenerated to its original state after product release.

Why does an enzyme remain unchanged overall after catalysis?

Although an enzyme may undergo temporary conformational changes or chemical interactions during catalysis, it is regenerated when products are released. Thus, one enzyme molecule can catalyze many reaction cycles.

How does temperature affect enzyme-catalyzed reaction rates?

Increasing temperature generally increases reaction rate because particles have greater average kinetic energy and collide more effectively. Above an enzyme's optimal range, disruption of its structure reduces activity and may cause denaturation.

Denaturation

Denaturation is a structural change that disrupts a biological molecule's normal conformation and function. In enzymes, extreme temperature or pH can alter the active site so that substrate binding and catalysis are impaired.

Why can extreme pH reduce enzyme activity?

Changes in pH alter the protonation and charge of amino acid side chains in the active site. This can disrupt substrate binding, catalytic interactions, or the enzyme's three-dimensional structure.

Why does each enzyme have an optimal temperature and pH range?

Enzyme activity depends on maintaining both an appropriate molecular structure and correctly charged active-site residues. Conditions outside the optimal ranges can reduce binding or catalysis, and sufficiently extreme conditions can denature the enzyme.

Competitive inhibition

In competitive inhibition, an inhibitor resembling the substrate binds to the enzyme's active site and prevents substrate binding. Increasing substrate concentration can often reduce the inhibitor's effect because substrate and inhibitor compete for the same site.

How does competitive inhibition affect reaction-rate behavior?

A competitive inhibitor lowers the reaction rate at a given substrate concentration, especially at lower concentrations. With enough substrate, the same maximum rate can generally be reached because the inhibitor can be outcompeted.

Noncompetitive inhibition

In noncompetitive inhibition, an inhibitor binds at a site other than the active site and reduces catalytic activity. Because it does not directly compete for substrate binding, increasing substrate concentration does not fully restore the maximum rate.

How do competitive and noncompetitive inhibition differ in their effects on maximum rate?

Competitive inhibition can be overcome by sufficiently high substrate concentration, so the maximum rate is not necessarily changed. Noncompetitive inhibition decreases the maximum rate because some enzyme molecules are rendered less effective regardless of substrate concentration.

Allosteric site

An allosteric site is a regulatory binding site distinct from an enzyme's active site. Binding at this site can change enzyme conformation and alter activity.

Allosteric inhibition

Allosteric inhibition occurs when an inhibitor binds away from the active site and changes the enzyme's conformation so substrate binding or catalysis becomes less effective. In multimeric enzymes, the conformational change can influence multiple subunits.

Allosteric activation

An allosteric activator binds at a regulatory site and changes the enzyme's conformation to increase the active site's affinity for substrate or improve catalysis.

Why can an allosteric regulator affect several active sites at once?

Many allosterically regulated enzymes contain multiple polypeptide subunits. A conformational change caused by regulator binding can be transmitted among subunits, altering the behavior of several active sites.

How do enzyme inhibitors and activators help cells control metabolism?

They alter the activity of enzymes that control reaction rates in metabolic pathways. This allows cells to match product formation and energy production to changing cellular conditions and demands.

Cofactor

A cofactor is a nonprotein helper, often an inorganic ion, required for some enzyme to function properly. Examples include metal ions such as $\mathrm{Mg^{2+}}$, $\mathrm{Fe^{2+}}$, or $\mathrm{Zn^{2+}}$.

Coenzyme

A coenzyme is an organic helper molecule required for the activity of some enzymes. Many coenzymes or their precursors are derived from dietary vitamins.

How do cofactors and coenzymes influence enzyme activity?

They can stabilize the enzyme's active conformation or participate in transferring electrons, atoms, or functional groups during a reaction. Without a required helper molecule, the enzyme may have greatly reduced activity or no activity.

What is the distinction between a cofactor and a coenzyme?

Cofactor is the broader term for a nonprotein helper and commonly refers to inorganic ions. A coenzyme is specifically an organic helper molecule.

How can the availability of cofactors and coenzymes regulate a metabolic pathway?

If a required helper molecule is scarce, the corresponding enzyme's activity decreases, slowing the pathway. Adequate supply allows the enzyme to adopt its functional form and catalyze the reaction.

Enzyme compartmentalization

Enzyme compartmentalization is the separation of enzymes and their substrates into specific cellular regions or organelles. It regulates reactions by controlling proximity and preventing incompatible reactions from occurring together.

How does compartmentalization improve control of enzyme-catalyzed reactions?

Placing an enzyme near its substrate can increase reaction efficiency, while separating it from other molecules can prevent unwanted reactions. In eukaryotes, mitochondria and lysosomes are examples of organelles containing specialized enzyme systems.

Metabolic pathway

A metabolic pathway is an ordered series of enzyme-catalyzed reactions in which the product of one step becomes the substrate for a later step. Regulation of one enzyme can therefore influence the entire pathway.

Feedback inhibition

Feedback inhibition occurs when the final product of a metabolic pathway inhibits an enzyme involved in an earlier step, often through allosteric binding. As the product accumulates, pathway activity decreases; when product levels fall, the pathway can resume.

Why is feedback inhibition an efficient way to prevent overproduction?

The pathway's own product provides the signal that sufficient product is present. Inhibiting an upstream enzyme reduces use of substrates and energy before additional unnecessary intermediates are produced.

How do ATP and ADP serve as opposing allosteric signals in cellular respiration?

High ATP levels can inhibit enzymes involved in sugar catabolism, reducing further ATP production. Relatively high ADP levels can activate some of these enzymes, signaling that the cell needs to produce more ATP.

How can enzyme regulation coordinate anabolism and catabolism?

Cells can inhibit pathways when their products or energy supplies are abundant and activate pathways when products or energy are needed. This prevents waste and maintains metabolic balance.

Why are enzymes useful targets for pharmaceutical drugs?

Blocking or activating a specific enzyme can alter a disease-related metabolic pathway while exploiting the enzyme's molecular specificity. Drug development requires identifying the target, understanding its pathway, and testing candidate molecules from laboratory studies through clinical trials.

How do statins lower cholesterol production?

Statins inhibit HMG-CoA reductase, an enzyme involved in cholesterol synthesis. Reduced activity of this enzyme decreases the amount of cholesterol synthesized by the body.

What is the relationship between enzyme structure and enzyme function?

An enzyme's specific three-dimensional structure determines the shape and chemical environment of its active and regulatory sites. Structural changes caused by pH, temperature, inhibitors, or activators can therefore change its activity.

Why can increasing substrate concentration fail to restore the activity of an inhibited enzyme?

If inhibition is noncompetitive or allosteric, the inhibitor changes the enzyme's conformation or catalytic ability rather than merely occupying the substrate's binding site. Additional substrate cannot fully compensate for the reduced number of functional enzyme molecules.

What happens to the rate of an enzyme-catalyzed reaction if enzyme concentration increases while substrate is abundant?

The reaction rate generally increases because more active sites are available to process substrate. The increase continues only while sufficient substrate is available and other conditions remain favorable.

What happens when substrate concentration becomes very high relative to enzyme concentration?

Most enzyme active sites become occupied, so the reaction approaches a maximum rate. Adding more substrate then produces little additional increase because enzyme availability becomes the limiting factor.

How do enzymes accelerate reactions without making unfavorable reactions spontaneous?

They reduce the kinetic barrier, $E_a$, but do not change $\Delta G$. A reaction with $\Delta G>0$ remains thermodynamically unfavorable and still requires an energy input or coupling to a favorable process.