Biochemistry W1-1

Biochemistry Overview

• Biochemistry describes the structures, mechanisms, and chemical processes shared by all organisms.
• It utilizes principles from chemistry and biology.
• The course will cover foundational concepts like chemistry, physics, energy, water, amino acids, peptides, proteins, carbohydrates, nucleotides, nucleic acids, fatty acids, glycolysis, and the electron transport chain.

Learning Objectives

• Understand fundamental concepts like chemistry, physics, energy, and water.
• Gain knowledge about amino acids, peptides, proteins, carbohydrates, nucleotides, nucleic acids, and fatty acids.
• Explore the processes of glycolysis and the electron transfer chain.

Chapter Specific Objectives

• Chemical Foundations:
  • Explore elements essential for animal life and health.
  • Understand the role of carbon in forming biomolecules and its ability to form single, double, and triple bonds.
  • Recognize the tetrahedral arrangement of carbon atoms and rotation around single and double bonds.
  • Be familiar with common functional groups in biomolecules.
• Physical Foundations:
  • Differentiate between open, closed systems, and the universe.
  • Understand energy transformation in living organisms, including energy extraction and oxidation-reduction reactions.
  • Explore concepts like entropy, enthalpy, and the relationship between Gibbs Free Energy (∆G), enthalpy (∆H), temperature (T), and entropy (dS): ∆ G = ∆ H- TdS.
  • Understand exergonic and endergonic reactions, equilibrium constant (Keq) and reaction quotient (Q), standard free energy change (∆G0), and the relationship between ∆G0 and Keq: ∆ G0 = -RT ln(Keq).
  • Distinguish between catabolism and anabolism.

Functional Groups of Biomolecules

• Functional groups contribute specific chemical properties to biomolecules, forming various families of organic compounds.
• Thioesters are important functional groups in biomolecules.

Central Metabolites

• Amino acids, nucleotides, sugars and their phosphorylated derivatives, mono- di-, and tricarboxylic acids are all central metabolites.
• Secondary metabolites are specific to the organism.
• The metabolome is the entirety of small molecules in a cell under specific conditions.
• Metabolomics is the systematic study of the metabolome under specific conditions.

Macromolecules

• Macromolecules are polymers with molecular weights greater than 5,000.
• Proteins, nucleic acids and polysaccharides are macromolecules.
• Oligomers are shorter polymers.
• Informational macromolecules are proteins, nucleic acids, and some oligosaccharides that contain information in their subunit sequences.

Protein Macromolecules

• Proteins are long polymers of amino acids.
• Proteins can function as enzymes, structural elements, signal receptors, and transporters.
• The proteome is all the proteins in a cell
• Proteomics is the systematic study of the proteome in specific conditions.

Nucleic Acid Macromolecules

• Nucleic acids are DNA and RNA, which are polymers of nucleotides.
• Nucleic acids store and transmit genetic information.
• Some RNA molecules are structural and catalytic in supramolecular complexes.
• The genome is the entire sequence of DNA or RNA in a cell.
• Genomics is the study of the structure, function, evolution and mapping of genomes.

Polysaccharide Macromolecules

• Polysaccharides are polymers of simple sugars.
• They are energy-rich fuels stores.
• They are rigid structural components of cell walls in plants and bacteria.
• They are extracellular recognition elements that bind to proteins on other cells.
• The glycome is the entirety of carbohydrate containing molecules.

Lipid Molecules

• Lipids are water-insoluble hydrocarbon derivatives.
• They are structural components of membranes.
• They are energy-rich fuel stores.
• They are pigments.
• They are intracellular signals.
• The lipidome is all the lipid containing molecules in a cell.

E. coli Cell Composition

• Water, proteins, nucleic acids, polysaccharides, lipids, monomeric subunits and intermediates, and inorganic ions are the major molecular components of an E. coli cell.

Metabolomics

• Metabolomics studies the changes in small molecules in a cell under specific conditions.

Stereochemistry

• Configuration is the fixed spatial arrangement of atoms.
• Stereoisomers are molecules with the same chemical bonds and same chemical formula.
• Stereointeractions are specific conformations interactions between biomolecules.

Geometric Isomers

• Geometric isomers, also referred to as cis-trans isomers, are compounds with variations in the spatial arrangement of their substituent groups around a double bond.

Chirality and Achiral Molecules

• Chiral centers represent asymmetric carbons.
• A molecule can have 2^n stereoisomers, where 'n' signifies the number of chiral carbons.

Enantiomers and Diastereomers

• Enantiomers are non-superimposable mirror images of each other.
• Diastereomers are stereoisomers that are not mirror images of each other.

Optical Activity of Enantiomers

• Enantiomers exhibit nearly identical chemical reactivity, but differ in their optical activity.
• A racemic mixture, composed of equal amounts of two enantiomers, displays no optical rotation.
• Plane-polarized light is generated by passing ordinary light through a polarizing filter.

Molecular Conformation

• Conformation refers to the spatial organization of substituent groups, which can adopt different positions in space.

Biological Systems and Stereochemistry

• Biological systems utilize a limited set of carbon-based metabolites to construct polymeric machines, supramolecular structures, and information repositories.
• The chemical structure of these components dictates their cellular function.
• This collection of molecules executes a designated program, resulting in the replication of the program and the self-perpetuation of the molecular collection – essentially, life.

Stereospecificity in Biological Systems

• Stereospecificity represents the ability to discern between stereoisomers.

Stereospecificity In Biomolecular Interactions

• Interactions between biomolecules are stereospecific.
• Hexokinase, an enzyme involved in phosphorylating hexoses, provides an example of this specificity, where it interacts with glucose in a specific orientation.

Stereochemistry and Drug Activity

• Celexa, an antidepressant medication, exists as a racemic mixture of two stereoisomers. However, only the (S)-citalopram enantiomer possesses therapeutic effects.
• Lexapro, a stereochemically pure preparation of (S)-citalopram, represents an example of how chirality impacts drug activity.
• The effective dose of Lexapro is half the effective dose of Celexa, as Celexa contains both enantiomers.

Living Organisms and Steady State

• Living organisms exist in a dynamic steady state, not at equilibrium with their surroundings
• This state is maintained by continuous synthesis and breakdown of molecules, from small molecules to supramolecular complexes
• Living cells maintain a dynamic steady state far from equilibrium

Thermodynamic Systems

• A system includes all reactants, products, solvents, and the immediate atmosphere
• The universe is composed of the system and its surroundings
• There are three types of systems:
  • Isolated systems exchange neither matter nor energy with their surroundings
  • Closed systems exchange energy but not matter with their surroundings
  • Open systems exchange both energy and matter with their surroundings
• Living organisms are open systems

Energy Transformation in Living Organisms

• The first law of thermodynamics states that the total amount of energy in the universe remains constant, though its form may change
• Organisms transform energy and matter from their surroundings
• Photoautotrophs harness energy from sunlight
• Chemotrophs obtain energy from chemical sources

Oxidation-Reduction Reactions

• Autotrophs and heterotrophs participate in global cycles of O2 and CO2, driven by sunlight
• Oxidation-reduction reactions involve the transfer of electrons, with one reactant being oxidized (losing electrons) and another being reduced (gaining electrons)

Creating and Maintaining Order Requires Work and Energy

• The second law of thermodynamics states that randomness (entropy) in the universe increases constantly
• Entropy (S) represents the randomness or disorder of a system
• Enthalpy (H) reflects the heat content, indicating the number and types of bonds
• Free energy (G) of a closed system is calculated as G = H – TS, where T is the absolute temperature
• Free-energy change (ΔG) is calculated as ΔG = ΔH − TΔS, where ΔH is negative for heat-releasing reactions and ΔS is positive for reactions increasing randomness
• Spontaneous reactions occur when ΔG is negative

Coupling Reactions

• Energy-requiring (endergonic) reactions are often coupled to energy-releasing (exergonic) reactions
• The breakdown of phosphoanhydride bonds in ATP is highly exergonic, providing energy for other processes

Free Energy Change

• Free energy change, denoted as ∆G, quantifies the amount of energy available to do work.
• It's always less than the theoretical amount of energy released in a reaction.

Energy Coupling

• In closed systems, chemical reactions proceed spontaneously until equilibrium is reached.
• This means that when the forward and reverse reaction rates are equal, the net change in free energy is zero.

Equilibrium Constant (Keq)

• The equilibrium constant, Keq, expresses the ratio of product concentrations to reactant concentrations at equilibrium.
• It's a measure of a reaction's tendency to proceed spontaneously.

Mass-Action Ratio (Q)

• The mass-action ratio, Q, is the ratio of product concentrations to reactant concentrations at a given time.
• This ratio can be compared to the equilibrium constant (Keq). If Q is less than Keq, the reaction will proceed forward toward equilibrium. If Q is greater than Keq, the reaction will proceed backward toward equilibrium.

ATP Breakdown

• The breakdown of ATP (adenosine triphosphate) into ADP (adenosine diphosphate) and inorganic phosphate (Pi) has a Keq of 2 x 10^5 M.
• If the cellular concentrations of ATP, ADP, and Pi are 15 mM, 1.5 mM, and 15 mM respectively, this reaction is not at equilibrium in living cells.
• This is because the calculated Q value is not equal to the Keq value. This indicates the reaction is not at equilibrium and is actively being used by the cell.