Introduction to Metabolism

General Overview of Energy

• Energy: The ability to cause change or do work.

  • Two General Forms:

  • Kinetic Energy: Associated with movement.

  • Potential Energy: Due to structure or location.

    • Chemical (Potential) Energy: Energy stored in atoms and molecular bonds that can be released during chemical reactions.

Laws of Thermodynamics

• First Law of Thermodynamics:

  • Also known as the Law of Conservation of Energy.

  • States that the energy of the universe is constant.

  • Energy cannot be created or destroyed, but can be transferred and transformed.

  • Application: Essential in bioenergetics.

• Second Law of Thermodynamics:

  • States that every energy transfer or transformation increases the Entropy of a system.

  • Entropy increases because some energy is lost to the surroundings as heat.

  • Heat increases the disorder of the surroundings.

  • Application: Essential in bioenergetics.

Biological Order and Disorder

• Cells and Organisms:

  • Create ordered structures from less organized starting materials.

  • Replace ordered forms of matter and energy with less ordered forms.

  • The evolution of complex organisms does not violate the second law of thermodynamics.

  • Total entropy of the universe increases, while organisms maintain low entropy at the expense of energy.

Thermodynamic Equations

• Gibbs Free Energy Equation:
  H = G + TS

  • Where:

  • H: Total energy (enthalpy)

  • G: Free energy (energy available to do work)

  • T: Temperature in Kelvin

  • S: Entropy (unusable energy)

• Change in Free Energy ([\Delta G]):

  • \Delta G = G{final} - G{initial}

  • Indicates whether a reaction occurs spontaneously.

  • If \Delta G < 0: Reaction is exergonic (spontaneous, releases energy).

  • If \Delta G > 0: Reaction is endergonic (non-spontaneous, requires energy).

Chemical Equilibrium

• Chemical Equilibrium:

  • Forward and reverse reactions occur at the same rate.

  • Work is possible only when \Delta G < 0 (reaction can proceed and do work).

  • In isolated systems, energy transformations can reach equilibrium, limiting work output.

• Open System:

  • Energy continues to be available for work as fresh reactants are provided.

  • Example: A hydroelectric system maintains flow, preventing equilibrium and allowing continuous work.

Types of Work in Cells

• Cells perform three main kinds of work:

  • Chemical Work: Energy used to synthesize complex molecules (endergonic reactions).

  • Mechanical Work: Movement of cellular components (e.g., cilia via motor proteins).

  • Transport Work: Movement of substances across membranes.

ATP and Energy Transfer

• Hydrolysis of ATP:

  • \Delta G = -7.3 \, kcal/mol

  • Reaction favors formation of products due to repulsive forces among negatively charged phosphate groups.

  • Energy liberated from ATP hydrolysis drives various cellular processes.

• ATP Regeneration:

  • Each ATP molecule goes through approx. 10,000 cycles of hydrolysis and re-synthesis daily.

  • Synthesis coupled to exergonic reactions; hydrolysis coupled to endergonic reactions.

Energy Coupling in Cells

• Cells manage energy resources by energy coupling:

  • Use of an exergonic process to drive an endergonic one.

  • Most energy coupling in cells is mediated by ATP.

  • Example: Glutamine synthesis from Glutamic Acid involves phosphorylation of Glu followed by the formation of Glutamine, resulting in a net negative \Delta G for the overall process.

Enzyme Functionality

• Enzymes and Ribozymes:

  • Catalysts: Speed up reactions without being consumed.

  • Enzymes: Proteins that act as catalysts.

  • Ribozymes: RNA molecules with catalytic properties.

• Activation Energy ([EA]):

  • Energy required to start a reaction by breaking bonds in reactant molecules.

  • Transition State: Unstable state where bonds are stretched.

  • Ways to overcome EA:

  • Large heat.

  • Enzymes to lower activation energy, which does not affect \Delta G.

Mechanism of Enzyme Action

• Enzymes Lower EA:

  • Positioning substrates to facilitate bonding.

  • Straining bonds in reactants to facilitate reaching the transition state.

  • Modifying the local environment to favor the reaction.

• Specificity of Enzymes:

  • Each enzyme is specific to its substrate (reactant molecule).

  • Active Site: Region on the enzyme that binds the substrate, forming the enzyme-substrate complex.

  • Specificity arises from the geometric fit between the active site and the substrate.

• Induced Fit Model:

  • Enzymes undergo conformational changes upon substrate binding, facilitating the reaction.

Enzyme Kinetics

• Enzyme-Catalyzed Reactions:

  • Saturation behavior observed with increasing substrate concentration, leading to a plateau where nearly all active sites are occupied.

  • Michaelis Constant (KM): Substrate concentration at which reaction velocity is half its maximal value.

  • Vmax: Maximum rate of the reaction achieved.

Enzyme Inhibition

• Types of Inhibition:

  • Competitive Inhibition:

  • Inhibit substrate binding by occupying the active site.

  • Requires an increased substrate concentration to reach Vmax.

  • Noncompetitive Inhibition:

  • Decreases Vmax without affecting KM; inhibitor binds to an allosteric site.

• Example of ACE Inhibitors:

  • Competitively bind to Angiotensin I-Converting Enzyme (ACE) impacting blood pressure regulation by affecting sodium and water reabsorption.

Regulation of Enzyme Activity

• Factors Affecting Enzyme Activity:

  • Prosthetic Groups: Small permanent molecules (e.g., heme) attached to enzymes.

  • Cofactors: Temporary inorganic ions needed for enzyme activity.

  • Coenzymes: Organic molecules that participate in reactions but remain unchanged after.

Environmental Factors

• Temperature and pH: Significant factors influencing enzyme activity and reaction rate.

  • Optimal temperature for typical human enzymes is 37^{\circ}C; thermophilic bacteria may have optimal temperatures around 75^{\circ}C.

  • Different enzymes exhibit varying pH optima.

Metabolism Overview

• Metabolism: The sum of all chemical reactions in a cell, providing energy and components for essential functions, including synthesis and breakdown.

• Metabolic pathways start with specific molecules and proceed through a series of enzyme-catalyzed reactions to reach final products.

• Cells remain out of equilibrium, constantly influxing and effluxing materials, preventing stagnation.

Catabolic and Anabolic Pathways

• Anabolic Pathways:

  • Consume energy to build complex molecules from simpler ones (biosynthetic pathways).

• Catabolic Pathways:

  • Release energy through the breakdown of complex molecules into simpler compounds (such as during cellular respiration).

• Cellular Respiration Example:

  • Breakdown of glucose and other fuels to yield energy, specifically ATP and reduced coenzymes (NADH).

ATP Synthesis Mechanisms

• Substrate-Level Phosphorylation:

  • Direct transfer of a phosphate group, not requiring oxygen.

• Chemiosmosis (Oxidative Phosphorylation):

  • Uses energy stored in an electrochemical gradient to produce ATP from ADP and inorganic phosphate (Pi).

Redox Reactions

• Basic Definitions:

  • Oxidation: Removal of electrons (substance loses electrons).

  • Reduction: Addition of electrons (substance gains electrons).

  • Mnemonic: Oxidation Is Losing; Reduction Is Gaining.

• Electron Transfer:

  • Electrons from organic compounds are transferred to NAD+ as an electron acceptor, functioning as an oxidizing agent in cellular respiration.

  • Each NADH represents stored energy for ATP synthesis and contributes to the energetic viability of synthesis reactions.

Metabolic Regulation

• Regulation Mechanisms:

  • Gene Regulation: Turning genes on or off to control enzyme production.

  • Cellular Regulation: Involves hormones and cellular signaling pathways.

  • Biochemical Regulation:

  • Feedback Inhibition: Auto-regulatory mechanism where the product of a pathway inhibits an early step, preventing overproduction.

  • Allosteric Regulation: Regulatory molecules bind to sites other than the active site, influencing the enzyme's functionality either negatively or positively.