Biology 1: Energy, Enzymes, and Metabolism

Fundamental Physical Principles of Energy in Biological Systems

• Energy is defined as the capacity to do work or the capacity to change.

• All forms of energy are categorized into two primary types:

  • Potential Energy: This is stored energy. Examples in biology include energy stored in chemical bonds, concentration gradients, and charge imbalances.

  • Kinetic Energy: This is the energy of movement.

Energy Conversion and Work

• Energy can be converted from one form to another to perform work.

• Example of internal conversion: The conversion of potential energy within chemical bonds into potential energy in the form of ATP (Adenosine Triphosphate).

• Example of external conversion: Light energy is converted into chemical energy in the eyes, which is then converted into electrical energy in nerve cells.

The Laws of Thermodynamics

• First Law of Thermodynamics: The total amount of energy before a transformation is equal to the total amount of energy after the transformation. This principle dictates that no new energy is created and no energy is lost.

• Second Law of Thermodynamics: While a transformation does not change the total amount of energy in a closed system, the amount of energy available to do work (free energy) after any transformation is always less than the original amount.

• Entropy: Another statement of the second law is that in a closed system with repeated energy transformations, free energy decreases and unusable energy increases. This phenomenon is known as the creation of entropy (disorder).

Mathematical Principles of Free Energy

• Total energy is the sum of usable energy and unusable energy.

• The formula for Enthalpy ($H$) is:     $H = G + TS$

• Variables defined:

  • $H$ = Enthalpy (Total energy)

  • $G$ = Free Energy (Usable energy)

  • $T$ = Temperature (Measured in Kelvin, always positive)

  • $S$ = Entropy (Disorder/Unusable energy)

• The change in free energy ($\Delta G$) is calculated by:     $\Delta G = \Delta H - T\Delta S$

• According to the Second Law, entropy tends to increase during energy transformations, meaning some energy is always "lost" to disorder.

Exergonic and Endergonic Reactions

• Chemical reactions occur when atoms change their bonding partners. The change in free energy ($\Delta G$) in a reaction is the difference in free energy between the products and the reactants:     $\Delta G = G_{\text{products}} - G_{\text{reactants}}$

• Exergonic Reactions: These reactions have a \Delta G < 0. Free energy is released during the process.

• Endergonic Reactions: These reactions have a \Delta G > 0. These require an input of free energy to proceed.

• Spontaneous Reactions: Reactions occur spontaneously when the change in free energy is negative (\Delta G < 0).

Examples of Thermodynamics in Physical States and Chemical Reactions

• Ice to liquid water: \Delta H > 0 and \Delta S > 0. Ice melts at high temperatures ($T$).

• Liquid water to ice: \Delta H < 0 and \Delta S < 0. Water freezes at low temperatures ($T$).

• If the products of a chemical reaction are more disordered than the reactants, entropy increases.

• Example: The hydrolysis of a protein into its individual amino acids results in \Delta S > 0.

Metabolism: Anabolism and Catabolism

• Metabolism is the sum total of all chemical reactions occurring in a biological system.

• Anabolic Reactions:

  • Complex molecules are synthesized from simple molecules.

  • These are endergonic reactions, requiring an input of free energy (\Delta G > 0).

  • The captured energy is stored in the resulting chemical bonds.

• Catabolic Reactions:

  • Complex molecules are broken down into simpler ones.

  • These are exergonic reactions, where free energy is released (\Delta G < 0).

  • The released energy can be used to form new chemical bonds or provide kinetic energy.

Adenosine Triphosphate (ATP) Structure and Function

• ATP is the primary molecule used to capture and transfer free energy.

• Structure components:

  • Adenine (nitrogenous base)

  • Ribose (sugar)

  • Three Phosphate groups

• Free energy is stored specifically in the $P-O$ (phosphate-oxygen) bonds.

• ATP Hydrolysis: $ATP + H_2O \rightarrow ADP + P_i + \text{energy}$.

• Energy specifics:

  • $1\,\text{mole} \approx 6 \times 10^{23}\text{ particles}$.

  • A typical cell contains approximately $10^9$ ATP molecules.

  • ATP is turned over every 1 to 2 minutes.

  • Each ATP hydrolysis event releases approximately $30\,kJ/mol$ or $7.3\,kcal/mol$ of energy.

• ATP can phosphorylate other molecules, meaning it donates a phosphate group to them.

Coupling Reactions

• Biological systems use energy coupling to drive non-spontaneous reactions.

• An exergonic reaction (like ATP hydrolysis) is paired with an endergonic reaction.

• Example: Synthesis of Glutamine:

  • Reaction: $\text{Glutamate} + NH_3 \rightarrow \text{Glutamine}$

  • Endergonic requirement: $\Delta G = +3.4\,kcal/mol$.

  • ATP Hydrolysis: $\Delta G = -7.3\,kcal/mol$.

  • Net Reaction: $\Delta G = -3.9\,kcal/mol$.

  • Because the net $\Delta G$ is negative, the coupled reaction becomes exergonic and proceeds toward completion.

Enzymes and Activation Energy

• Activation Energy ($E_a$): For a chemical reaction to occur, reactants must be charged with a specific amount of energy to reach a transition state. This energy requirement exists for both endergonic and exergonic reactions.

• $E_a$ and Rates: $E_a$ does not change the final reaction equilibrium (which is determined by $\Delta G$), but it determines the rate of the reaction. Higher activation energy leads to a slower reaction.

• Catalyst: A substance that accelerates a chemical reaction by lowering the activation energy ($E_a$).

• Enzyme: A biological catalyst, usually a protein, that speeds up reactions in cells. Enzymes are highly specific to particular reactions and do not affect the $\Delta G$ or the final equilibrium state.

Enzyme Mechanisms and the Active Site

• Substrates bind to the enzyme's active site.

• Substrate-Enzyme Interaction: $E + S \rightarrow ES \rightarrow E + P$

• Enzymes lower the activation energy through several methods:

  • Orientation: Orienting substrates so they can interact effectively.

  • Physical Strain: Inducing strain in the substrate to put it into an unstable transition state.

  • Chemical Modification: Temporarily adding chemical groups to substrates to make them more reactive.

• Induced Fit: Some enzymes change their spatial structure (shape) upon binding a substrate. Example: Hexokinase changes shape when binding glucose and ATP.

• Saturation: Catalyzed reactions have a maximum rate. At this point, all enzyme molecules are occupied by substrate molecules. Increasing substrate concentration further will not increase the rate.

Regulation of Enzyme Activity

• Cofactors and Coenzymes:

  • Many enzymes require additional molecules to function.

  • Coenzymes are non-protein, carbon-containing molecules required for some enzyme functions.

• Reversible Inhibition:

  • Competitive Inhibitors: Bind to the active site, competing directly with the substrate.

  • Non-competitive Inhibitors: Bind to an allosteric site (a site other than the active site), changing the enzyme's shape. This type of inhibition is not sensitive to substrate concentration.

  • Uncompetitive Inhibitors: Bind specifically to the Enzyme-Substrate ($ES$) complex.

  • Allosteric Regulation: The change in enzyme shape due to non-competitive binding, which alters the affinity of the active site for the substrate. It includes both inhibitors and activators.

• Feedback Inhibition: The end-product of a metabolic pathway allosterically inhibits the enzyme catalyzing the first reaction step (the commitment step). This shuts down the production once enough product has accumulated.

Metabolic Pathways

• Complex chemical transformations occur through a series of connected reactions forming a network.

• Principles governing metabolic pathways:

  • Each reaction is catalyzed by a specific enzyme.

  • Pathways are similar across almost all organisms.

  • In eukaryotes, pathways are compartmentalized within specific organelles.

• Enzyme Nomenclature: Names often include the substrate or activity followed by the suffix "-ASE". Example: "Histidine phosphatase".

Glucose Metabolism and Energy Harvesting

• The most common fuel for organisms is glucose ($C_6H_{12}O_6$).

• Complete combustion of glucose: $C_6H_{12}O_6 + 6O_2 \rightarrow 6CO_2 + 6H_2O + \text{free energy}$.

• $\Delta G$ for glucose combustion is $-686\,kcal/mol$.

• Approximately one-third ($\sim 1/3$) of this energy is captured as ATP in metabolic pathways.

• Pathways involved:

  • Glycolysis: The initial breakdown of glucose into pyruvate.

  • Pyruvate Oxidation: Occurs if oxygen is present.

  • Citric Acid Cycle (Krebs Cycle).

  • Electron Transport Chain.

  • Fermentation: Occurs if oxygen is absent, resulting in lactate or alcohol.

Cellular Locations for Energy Pathways

• Eukaryotes:

  • Cytoplasm (external to mitochondrion): Glycolysis, Fermentation.

  • Mitochondrial Matrix: Pyruvate oxidation, Citric acid cycle.

  • Inner Mitochondrial Membrane: Electron transport chain.

• Prokaryotes:

  • Cytoplasm: Glycolysis, Fermentation, Citric acid cycle.

  • Plasma Membrane: Pyruvate oxidation, Electron transport chain.

Redox Reactions: Oxidation and Reduction

• Redox reactions involve the transfer of electrons between substances.

• Oxidation: The loss of one or more electrons.

• Reduction: The gain of one or more electrons, resulting in a reduced electrical charge.

• Mnemonic: "OIL RIG" (Oxidation Is Losing, Reduction Is Gaining).

• Oxidation and reduction always occur together.

• The reducing agent (reducer) is the reactant that becomes oxidized; it causes another substance to be reduced.

• The oxidizing agent (oxidizer) is the reactant that becomes reduced; it causes another substance to be oxidized.

• Electronegativity: The attractive force an atomic nucleus exerts on shared electrons. Oxygen has high electronegativity ($3.5$), carbon is medium ($2.5$), and hydrogen is lower ($2.1$).

• Energy storage and Redox: A carbon atom stores less free energy the more oxidized it is.

NAD as an Electron Carrier

• The coenzyme NAD (Nicotinamide adenine dinucleotide) serves as a key electron carrier.

• It exists in two forms:

  • $NAD^+$: The oxidized form (empty).

  • $NADH + H^+$: The reduced form (loaded).

• Reduction Reaction: $NAD^+ + H^+ + 2e^- \rightarrow NADH$

• Oxidation Reaction: $NADH + H^+ + \frac{1}{2}O_2 \rightarrow NAD^+ + H_2O$

• The oxidation of NADH is highly exergonic, releasing $52.4\,kcal/mol$ of free energy. In comparison, ATP is a smaller package of energy ($7.3\,kcal/mol$).