Energy, Enzymes, and Metabolism

6Energy, Enzymes, and

Metabolism

6 Energy, Enzymes, and Metabolism

• 6.1 What Physical Principles Underlie Biological Energy Transformations?

• 6.2 What Is the Role of ATP in Biochemical Energetics?

• 6.3 What Are Enzymes?

• 6.4 How Do Enzymes Work?

• 6.5 How Are Enzyme Activities Regulated?

6.1 What Physical Principles Underlie Biological Energy Transformations?

The transformation of energy is a hallmark of life.

Energy is the capacity to do work, or the capacity to change.

Energy transformations are linked to chemical transformations in cells.


All forms of energy can be placed in two categories:

• Potential energy is stored energy—as chemical bonds, concentration gradient, charge imbalance, etc.

• Kinetic energy is the energy of movement.

Figure 6.1 Energy Conversions and Work


Metabolism: sum total of all chemical reactions in an organism

Anabolic reactions: complex molecules are made from simple molecules; energy input is required.

Catabolic reactions: complex molecules are broken down to simpler ones and energy is released.


First Law of Thermodynamics: Energy is neither created nor destroyed.

When energy is converted from one form to another, the total energy before and after the conversion is the same.


Second Law of Thermodynamics: When energy is converted from one form to another, some of that energy becomes unavailable to do work.

No energy transformation is 100 percent efficient.

Figure 6.2 The Laws of Thermodynamics


In any system:

total energy = usable energy + unusable energy

Enthalpy (H) = Free Energy (G) + Entropy (S)

or H = G + TS (T = absolute temperature)

G = H – TS


Change in energy can be measured in calories or joules.

Change in free energy (ΔG) in a reaction is the difference in free energy of the products and the reactants.


ΔG = ΔH – TΔS

If ΔG is negative, free energy is released.

If ΔG is positive, free energy is consumed.

If free energy is not available, the reaction does not occur.


Magnitude of ΔG depends on:

ΔH—total energy added (ΔH > 0) or released (ΔH < 0).

ΔS—change in entropy. Large changes in entropy make ΔG more negative.


If a chemical reaction increases entropy, the products will be more disordered.

Example: hydrolysis of a protein into its component amino acids—ΔS is positive.


Second Law of Thermodynamics:

Disorder tends to increase because of energy transformations.

Living organisms must have a constant supply of energy to maintain order.


Exergonic reactions release free energy (–ΔG)—catabolism

Endergonic reactions consume free energy (+ΔG)—anabolism

Figure 6.3 Exergonic and Endergonic Reactions


In principle, chemical reactions can run in both directions.

Chemical equilibrium ΔG = 0

Forward and reverse reactions are balanced.

BA

Figure 6.4 Chemical Reactions Run to Equilibrium


Every reaction has a specific equilibrium point.

ΔG is related to the point of equilibrium: the further towards completion the point of equilibrium is, the more free energy is released.

ΔG values near zero—characteristic of readily reversible reactions.

6.2 What Is the Role of ATP in Biochemical Energetics?

ATP (adenosine triphosphate) captures and transfers free energy.

ATP releases a large amount of energy when hydrolyzed.

ATP can phosphorylate, or donate phosphate groups to other molecules.


ATP is a nucleotide.

Hydrolysis of ATP yields free energy.

ΔG = –7.3 kcal/mole

energyfreePADPOHATP i 2

Figure 6.5 ATP (A)


Bioluminescence—an endergonic reaction

lightPPAMPinoxyluciferATPOluciferin iluciferase 2

Figure 6.5 ATP (B)

Figure 6.6 Coupling of Reactions

Exergonic and endergonic reactions are coupled.

Figure 6.7 Coupling of ATP Hydrolysis to an Endergonic Reaction

6.3 What Are Enzymes?

Catalysts speed up the rate of a reaction.

The catalyst is not altered by the reactions.

Most biological catalysts are enzymes (proteins) that act as a framework in which reactions can take place.


Some reactions are slow because of an energy barrier = the amount of energy required to start the reaction—activation energy (Ea)

Figure 6.8 Activation Energy Initiates Reactions


Activation energy changes the reactants into unstable forms with higher free energy—transition state species.

Activation energy can come from heating the system—the reactants have more kinetic energy.

Enzymes lower the energy barrier by bringing the reactants together.


Biological catalysts (enzymes and ribozymes) are highly specific.

Reactants are called substrates.

Substrate molecules bind to the active site of the enzyme.

Three-dimensional shape of the enzyme determines the specificity.

Figure 6.9 Enzyme and Substrate


The enzyme-substrate complex is held together by hydrogen bonds, electrical attraction, or covalent bonds.

E + S → ES → E + P

The enzyme may change when bound to the substrate, but returns to its original form.


Enzymes lower the energy barrier for reactions.

The final equilibrium doesn’t change, ΔG doesn’t change.

Figure 6.10 Enzymes Lower the Energy Barrier

Figure 6.11 Life at the Active Site (A)

Enzymes orient substrate molecules, bringing together the atoms that will bond.

Figure 6.11 Life at the Active Site (B)

Enzymes can stretch the bonds in substrate molecules, making them unstable.

Figure 6.11 Life at the Active Site (C)

Enzymes can temporarily add chemical groups to substrates.

6.4 How Do Enzymes Work?

Acid-base catalysis: enzyme side chains transfer H+ to or from the substrate—a covalent bond breaks

Covalent catalysis: a functional group in a side chain bonds covalently with the substrate

Metal ion catalysis: metals on side chains loose or gain electrons


Shape of enzyme active site allows a specific substrate to fit—the “lock and key.”

Many enzymes change shape when they bind to the substrate—induced fit.

Figure 6.12 Some Enzymes Change Shape When Substrate Binds to Them


Some enzymes require “partners”:

• Prosthetic groups: non-amino acid groups bound to enzymes

• Cofactors: inorganic ions

• Coenzymes: not bound permanently to enzymes

Figure 6.13 An Enzyme with a Coenzyme


The rate of a catalyzed reaction depends on substrate concentration.

Concentration of an enzyme is usually much lower than concentration of a substrate.

At saturation, all enzyme is bound to substrate—maximum rate.

Figure 6.14 Catalyzed Reactions Reach a Maximum Rate


Rate can be used to calculate enzyme efficiency: molecules of substrate converted to product per unit time—also called turnover.

Ranges from 1 to 40 million molecules per second!

6.5 How Are Enzyme Activities Regulated?

Thousands of chemical reactions are occurring in cells simultaneously.

The reactions are organized in metabolic pathways. Each reaction is catalyzed by a specific enzyme.

The pathways are interconnected.

Regulation of enzymes and thus the rates of reactions helps maintain internal homeostasis.


Metabolic pathways can be modeled using mathematical algorithms.

This new field is called systems biology.

Figure 6.15 Metabolic Pathways


Inhibitors regulate enzymes: a molecule that binds to the enzyme and slows reaction rates.

Naturally occurring inhibitors regulate metabolism.


Irreversible inhibition: inhibitor covalently bonds to side chains in the active site—permanently inactivates the enzyme.

Example: DIPF or nerve gas

Figure 6.16 Irreversible Inhibition


Reversible inhibition: inhibitor bonds noncovalently to the active site, prevents substrate from binding—competitive inhibitors.

When concentration of competitive inhibitor is reduced, it detaches from the active site.

Figure 6.17 Reversible Inhibition (A)


Noncompetitive inhibitors: bind to the enzyme at a different site (not the active site).

The enzyme changes shape and alters the active site.

Figure 6.17 Reversible Inhibition (B)


Allostery (allo, “different”; stery, “shape”)

Some enzymes exist in more than one shape:

• Active form—can bind substrate

• Inactive form—cannot bind substrate but can bind an inhibition


Most allosteric enzymes are proteins with quaternary structure.

Active site is on one subunit, the catalytic subunit

Inhibitors and activators bind to the regulatory subunits

Figure 6.18 Allosteric Regulation of Enzymes

Figure 6.19 Allostery and Reaction Rate

(Sigmoid or S-shaped plot)


Metabolic pathways:

The first reaction is the commitment step—other reactions then happen in sequence.

The final product may allosterically inhibit the enzyme needed for the commitment step, which shuts down the pathway—feedback inhibition or end-product inhibition.

Figure 6.20 Feedback Inhibition of Metabolic Pathways


Every enzyme has an optimal pH.

pH influences the ionization of functional groups.

Example: at low pH (high H+) —COO– may react with H+ to form —COOH which is no longer charged—affects folding and thus enzyme function.

Figure 6.21 pH Affects Enzyme Activity


Every enzyme has an optimal temperature.

At high temperatures, noncovalent bonds begin to break.

Enzyme can lose its tertiary structure and become denatured.

Figure 6.22 Temperature Affects Enzyme Activity


Isozymes: enzymes that catalyze the same reaction but have different properties, such as optimal temperature.

Organisms can use isozymes to adjust to temperature changes.

Enzymes in humans have higher optimal temperature than enzymes in most bacteria—a fever can denature the bacterial enzymes.

Energy, Enzymes, and Metabolism

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