Foundations of Biochemistry and Water, the Solvent of Life
Foundations of Biochemistry
Characteristics of Living Matter
High complexity and organization: Living systems are intricately arranged.
Dynamic and coordinated interactions: Individual components interact precisely.
Energy use: Organisms extract, transform, and systematically use energy to build/maintain structures and do work.
Responsiveness: Ability to sense and react to changes in surroundings.
Self-replication: Capacity for precise self-replication while allowing for changes necessary for evolution.
The Cell: Universal Building Block
Basic unit of life: All living organisms are composed of cells.
Diversity: Simplest organisms are single-celled; larger organisms have many cells with specialized functions.
Common features: All cells share traits like a plasma membrane and cytoplasm.
Domains of Life
Organisms are categorized into three domains based on cellular and molecular differences:
Bacteria and Archaea: Unicellular prokaryotes.
Eukarya: Contains four kingdoms:
Protista: Unicellular eukaryotes.
Fungi: Unicellular and/or multicellular eukaryotes.
Plantae: Multicellular eukaryotes.
Animalia: Multicellular eukaryotes.
Molecular Composition and Cell Structures
Cells are built from molecules like sugars, proteins, lipids, and nucleic acids.
Example: Bacterial Cell Structures, Functions, and Compositions
Cell wall: Composed of peptidoglycan (sugar + protein); provides mechanical support.
Cell membrane: Composed of lipid + protein; acts as a permeability barrier.
Nucleoid: Composed of DNA + protein; stores genetic information.
Ribosomes: Composed of RNA + protein; responsible for protein synthesis.
Pili: Composed of protein; involved in adhesion and conjugation.
Flagella: Composed of protein; provides motility.
Cytoplasm: Aqueous solution; main site of metabolism.
Eukaryotic vs. Prokaryotic Cells
Eukaryotic cells are more complex than prokaryotic cells.
Membrane-enclosed organelles: Eukaryotes spatially separate energy-yielding and energy-consuming reactions.
Nucleus: Site of DNA metabolism, protects DNA, selectively imports/exports molecules via nuclear membrane pores.
Mitochondria: Found in animals, plants, and fungi; locations for many energetic reactions.
Chloroplasts: Found in plants; locations for photosynthesis.
Lysosomes: Used for controlled disposal and digestion of un-needed molecules.
Animal vs. Plant Cells
Plant cells have additional structures not found in typical animal cells:
Cell wall: Provides shape, rigidity, and protects from osmotic swelling.
Vacuole: Degrades and recycles macromolecules, stores metabolites.
Chloroplast: Harvests sunlight, produces ATP and carbohydrates.
Glyoxysome: Contains enzymes of the glyoxylate cycle.
Animal cells typically have a Peroxisome (oxidizes fatty acids) and a Lysosome (degrades intracellular debris), which are generally absent in plant cells.
Cytoplasm and Cytosol
Cytoplasm: All material between the plasma membrane and organelle interiors (biomolecules, water, etc.).
Cytosol: The highly viscous aqueous solution filling the cytoplasm where many reactions occur.
Crowded environment: Chemical reaction speeds, limited by diffusion, are slower inside cells than outside due to the crowded nature of the cytosol.
Cytoskeleton
Maintains dynamic cellular organization.
Composed of three protein types:
Microtubules: Provide intracellular transport paths, maintain cell shape, and enable cellular movement.
Actin filaments: Help maintain cell shape, intracellular organization, and allow cellular movement.
Intermediate filaments: Maintain cell shape and intracellular organization.
Chemical Foundations of Life
Essential Elements for Life
Approximately 30 elements are essential for life.
Bulk elements: Atoms present in organic molecules (H, C, N, O, P, S) and some ions ( ext{Na}^+, ext{Cl}^-, ext{K}^+, ext{Ca}^{2+}).
Trace elements: Metal ions (e.g., ext{Mg}^{2+}, ext{Zn}^{2+}, ext{Fe}^{2+}) crucial for metabolism.
Unique Role of Carbon
Carbon can form single, double, or triple covalent bonds, leading to a vast diversity of chemical structures.
Different bonding results in various geometrical shapes of molecules.
Carbon Bond Formation and Breaking
Heterolytic cleavage: More common than homolytic cleavage.
Products are ions (e.g., ext{H}^+, ext{H}-, ext{CH}3^+, ext{CH}3^-) that readily react to form new bonds.
Homolytic cleavage: Products are unstable, highly reactive radicals that can damage other molecules.
Nucleophiles and Electrophiles
Nucleophiles: Atoms with unpaired or extra electrons ( ext{ extdelta}- or $-$ charged atoms); electron-rich species.
Electrophiles: Atoms with electron deficiency ( ext{ extdelta}+ or $+$ charged atoms); electron-poor species.
Example of Bond Formation: A carbanion nucleophile reacts with a carbonyl carbon electrophile to form a carbon-carbon bond, generating a new negatively-charged oxygen nucleophile. This oxygen nucleophile can then react with a hydrogen ion (proton) electrophile to form an oxygen-hydrogen bond.
Molecular Structure and Function: Isomers
Isomers: Molecules with the same chemical formula but different arrangements of atoms.
Structural isomers: Have different physical and chemical properties due to distinct bonding arrangements.
Geometric isomers (cis and trans): Have different physical and chemical properties due to restricted rotation around specific bonds leading to different spatial arrangements.
Enantiomers: Non-superimposable mirror images of each other, possessing identical physical and chemical properties (except in chiral environments).
Diastereomers: Non-superimposable structures that are not mirror images of each other, possessing different physical and chemical properties.
Specificity of Biomolecular Interactions
Biomolecular interactions are highly specific.
Typically, only one molecular isomer (e.g., a specific enantiomer) will fit and bind effectively into a specific three-dimensional binding pocket of a protein.
Other isomers lack the correct geometry for effective binding.
Example: Stereoisomers of carvone smell differently because each isomer preferentially binds to distinct protein receptors in olfactory cells.
Common Functional Groups
Functional groups are crucial for molecular reactivity and interactions.
Examples from various biomolecules include:
Carboxyl (COO-): Found in amino acids, fatty acids.
Amino (NH2, NH3+): Found in amino acids, nucleotide bases.
Hydroxyl (OH): Found in sugars, alcohols, serine, threonine, tyrosine.
Thiol (SH): Found in cysteine, glutathione.
Methyl (CH3): Common in many organic molecules, nonpolar.
Carbonyl (C=O): Aldehyde and ketone groups, found in sugars.
Phosphate (PO4^2-): Found in nucleic acids, phospholipids, phosphorylated proteins.
Amido: Peptide bonds, asparagine, glutamine.
Phosphoanhydride: ATP, other nucleotide triphosphates.
Example: Acetyl-coenzyme A contains multiple functional groups: thioester, amido, hydroxyl, phosphoanhydride, phosphoryl, and amino groups.
The Building Blocks of Life
Amino Acids: Contain functional groups vital for protein structure and function.
Nucleic Acids: Composed of nitrogenous bases (A, G, C, T, U), five-carbon sugars (ribose, deoxyribose), and phosphate groups.
Lipids: Include components like glycerol, fatty acids (e.g., palmitate, oleate), and choline.
Sugars: Include simple sugars like ext{ extalpha}-D-Ribose, ext{2-deoxy- extalpha}-D-ribose, and ext{ extalpha}-D-Glucose.
Molecular Hierarchy of Structure
Almost all cellular components are constructed from these fundamental building blocks: nucleic acids, amino acids, sugars, and lipids.
Energy Transductions and Metabolism
Organisms Perform Energy Transductions
Life requires organisms to transform energy from one form to another rapidly enough to sustain biological processes.
Classification by Energy and Carbon Sources
Phototrophs: Obtain energy from sunlight.
Examples: Plants, algae, cyanobacteria, green & purple bacteria.
Chemotrophs: Obtain energy from chemical compounds.
Examples: Animals, fungi, protists, most other bacteria.
Organisms are further classified by their carbon source:
Autotrophs: Use ext{CO}_2 as their primary carbon source.
Photoautotrophs: Use light for energy and ext{CO}_2 for carbon (e.g., plants, algae, cyanobacteria).
Chemoautotrophs: Use chemicals for energy and ext{CO}_2 for carbon (e.g., hydrogen-, sulfur-, iron-, nitrogen-, and carbon monoxide-oxidizing bacteria).
Heterotrophs: Obtain carbon from organic compounds.
Photoheterotrophs: Use light for energy and organic compounds for carbon (e.g., green nonsulfur bacteria, purple nonsulfur bacteria).
Chemoheterotrophs: Use chemicals for energy and organic compounds for carbon (e.g., all animals; most fungi, protists, bacteria).
Chemical Reactions and Energy
Endergonic reactions: Absorb energy from surroundings.
Products have higher energy than reactants.
Change in free energy ( ext{ extDelta}G) is positive ( ext{ extDelta}G > 0).
Example: Synthesis of complex molecules requires energy.
Exergonic reactions: Release energy into surroundings.
Reactants have higher energy than products.
Change in free energy ( ext{ extDelta}G) is negative ( ext{ extDelta}G < 0).
Example: Breakdown of molecules often releases energy.
Thermodynamic Favorability vs. Kinetic Speed
In isolation, endergonic reactions are thermodynamically unfavorable ( ext{ extDelta}G > 0), and exergonic reactions are thermodynamically favorable ( ext{ extDelta}G < 0).
Thermodynamic favorability is distinct from kinetic speed.
Speed of a chemical reaction: Determined by the activation energy ( ext{ extDelta}G^ ext{ extddagger}) required to initiate the reaction.
Reactions with large ext{ extDelta}G^ ext{ extddagger} are slower than reactions with small ext{ extDelta}G^ ext{ extddagger}.
Examples of Reaction Energetics and Speed
Hydrolysis of ATP: Favorable and Slow
Removal of phosphoryl and/or phosphoanhydride groups from ATP to form ADP or AMP releases energy, making it favorable ( ext{ extDelta}G < 0).
However, the activation energy ( ext{ extDelta}G^ ext{ extddagger}) is large, so the reaction is generally slow without catalysis.
Phosphorylation of Glucose: Unfavorable and Slow
Addition of a phosphate group to glucose requires energy, making it unfavorable ( ext{ extDelta}G > 0).
The activation energy ( ext{ extDelta}G^ ext{ extddagger}) is large, so the reaction is generally slow without catalysis.
Energy Coupling: Making Unfavorable Reactions Favorable
Chemical coupling of an endergonic reaction with an exergonic reaction allows otherwise unfavorable reactions to proceed.
The total free energy change ( ext{ extDelta}G) for a coupled reaction is the sum of the individual free energy changes ( ext{ extDelta}G1, ext{ extDelta}G2).
Example:
Glucose + ext{P}_ ext{i}
ightarrow Glucose-6-Phosphate + ext{H}2 ext{O} ( ext{ extDelta}G^ ext{ extdegree}1 = 14 ext{ kJ/mol}, unfavorable)ATP + ext{H}2 ext{O} ightarrow ADP + ext{P} ext{i} ( ext{ extDelta}G^ ext{ extdegree}_2 = -30 ext{ kJ/mol}, favorable)
Coupled: Glucose + ATP
ightarrow Glucose-6-Phosphate + ADP ( ext{ extDelta}G^ ext{ extdegree} = ext{ extDelta}G^ ext{ extdegree}1 + ext{ extDelta}G^ ext{ extdegree}2 = -16 ext{ kJ/mol}, overall favorable)
Increasing Chemical Reaction Speed
Temperature increase: Raises energy in the environment, speeding up reactions. Not practical for living organisms due to macromolecule stability limits.
Reducing activation energy: This is the effective method in living organisms.
Catalysts (e.g., enzymes) are used to lower the activation energy barrier ( ext{ extDelta}G^ ext{ extddagger}).
Catalysis: Lowering Activation Energy
A catalyst increases the rate of a chemical reaction without being consumed.
Catalysts lower the activation energy ( ext{ extDelta}G^ ext{ extddagger}) but do not alter the total free energy change ( ext{ extDelta}G) of the reaction.
Enzymes are biological catalysts, typically proteins, characterized by:
Acceleration under mild conditions (physiological temperature, pH).
High specificity for their substrates.
Regulation of their activity.
Metabolism
Metabolism: The entire set of chemical reactions occurring in a cell.
Catabolic reaction pathways: Break down complex molecules (e.g., degradation of carbohydrates, lipids, amino acids).
These pathways are generally exergonic (release energy).
Anabolic reaction pathways: Synthesize complex molecules from simpler ones (e.g., synthesis of carbohydrates, lipids, amino acids).
These pathways are generally endergonic (require energy input).
Metabolism is tightly regulated through various processes to maintain cellular homeostasis.
Genetic and Evolutionary Foundations
Origin of Life
Earth formed approximately 4.5 billion years ago.
Life originated about 0.7 billion years later, roughly 3.8 billion years ago.
Miller-Urey experiment: Demonstrated that some essential molecules for life (e.g., aldehydes, amino acids) could form under abiotic conditions from early atmospheric components.
Abiotic Assembly of Complex Molecules
Simple molecules can self-assemble abiotically into more complex structures such as lipids, nucleic acids, and peptides.
These more complex molecules could then organize into early living systems.
RNA World Hypothesis
The ability to pass on genetic information was crucial for the continuation of life.
Hypothesis: RNA was the original genetic material.
Dual function: RNA could act both as an information carrier (like DNA) and as a biocatalyst (like proteins) for its own replication.
Ribozymes: RNA molecules with catalytic activity, supporting the idea of RNA as an early biocatalyst.
Transition to DNA
While RNA still encodes information and catalyzes some reactions, DNA is now the primary genetic material for most organisms due to its increased stability.
Reasons for DNA's stability over RNA:
Deoxyribose sugar: Contains one less oxygen atom than ribose (in RNA), preventing easy hydrolysis of phosphodiester linkages, which can readily occur in RNA.
Double-stranded nature: DNA typically forms a double helix, providing greater stability compared to the generally single-stranded RNA.
Specific hydrogen bonding: Precise base-pairing between nucleobases in DNA allows for more accurate replication, making DNA a more suitable and reliable genetic material.
RNA's Role in Gene Expression
Genetic information stored in DNA is copied into an RNA form (mRNA) through transcription.
This RNA then carries the instructions for making proteins, a process called translation, which occurs on ribosomes.
Proteins are the key functional molecules responsible for the vast majority of cellular processes.
Genetic Diversity and Evolution
Random mutations in DNA: Generate genetic diversity within organisms, leading to new traits.
Natural selection: Mutations that confer a survival or reproductive advantage in a particular environment are more likely to be passed on to offspring.
Example: Duplication and subsequent mutation of the hexokinase gene led to a similar protein capable of metabolizing a different sugar, providing an evolutionary advantage.
Evolution of Eukaryotes through Endosymbiosis
Early eukaryotic cells acquired energy-processing organelles, mitochondria and chloroplasts, by engulfing bacteria.
These engulfed bacteria were retained within the host cell, forming a symbiotic relationship and paving the way for eukaryotic cellular complexity.
Water, the Solvent of Life
Water: The Medium for Life
Ubiquity: Organisms typically consist of 70-90% water.
Aqueous reactions: Most biochemical reactions occur in an aqueous environment.
Structural determinant: Water is critical for the structure and function of proteins, nucleic acids, and membranes.
Protection: Water absorbs and reflects UV light, shielding organisms from damaging electromagnetic radiation.
Structure of the Water Molecule
Geometry: A distorted tetrahedron with four sp^3 orbitals around the oxygen atom.
Two electron pairs form covalent bonds with two hydrogen atoms.
Two electron pairs are nonbonding (lone pairs).
Electronegativity: The oxygen atom is highly electronegative, leading to a net dipole moment (a noncovalent interaction).
Hydrogen bonding: Water can act as both a hydrogen bond donor (via H atoms) and a hydrogen bond acceptor (via O atom lone pairs).
Hydrogen Bonds: A Type of Dipole-Dipole Interaction
Dipole interactions: Electrostatic interactions between uncharged polar molecules.
Hydrogen bonds: Specific dipole-dipole interactions occurring between:
A hydrogen donor: A hydrogen atom covalently bonded to a highly electronegative atom (e.g., -OH and -NH functional groups).
A hydrogen acceptor: An electronegative atom with a lone pair of electrons (e.g., R-O-R, C=O, and R-N=R functional groups).
Strength of hydrogen bonds: Influenced by geometry and distance.
Orientation: Strongest when the three atoms involved are collinear, maximizing electrostatic interaction.
Distance: Strongest within an optimal range of 0.18 - 2.2 ext{ nm}. Strong interactions occur when atoms are closer (e.g., 0.18 ext{ nm}), weakening as distance increases.
Other Types of Noncovalent Interactions
Ionic interactions (salt bridges): Electrostatic interactions between permanently charged atoms or molecules, or between an ion and a permanent dipole.
Hydrophobic effect: Associated with minimizing the structural order of water molecules around nonpolar substances. It is not an attractive force between hydrophobic molecules, but rather an indirect effect driven by the increase in water entropy.
Van der Waals interactions (London dispersion forces): Weak, transient interactions occurring between any two atoms that are close to each other.
Random variations in electron positions create temporary dipoles that weakly attract each other (typically at 0.4 - 0.7 ext{ nm} apart).
The van der Waals radius of an atom defines how close it can approach another atom (typically < 0.2 ext{ nm}) before electron cloud repulsion occurs.
Additive Strength of Weak Interactions
Individually weak interactions become very strong when they are numerous and added together.
Example: Gecko feet adhesion:
Gecko feet have cellular extensions (setae and spatulae) made of keratin protein.
Each spatulae makes atomic-scale contact with a surface, generating attachment energy through van der Waals interactions.
With approximately 1 billion spatulae, the combined van der Waals forces are immense, supporting over 100 ext{ kg} of weight (more than 1000 times the gecko's own weight).
Cooperative Hydrogen Bonding in Water
Each water molecule can form up to four hydrogen bonds, which accounts for water's unique properties.
Unique properties:
High melting point and boiling point relative to its small molecular mass.
Unusually large surface tension.
Ice vs. Liquid Water:
Ice: Contains more hydrogen bonds per water molecule, forming a regular, open lattice structure. This leads to ice having a lower density than liquid water.
Liquid water: Water molecules move freely, and hydrogen bonds constantly break and reform, resulting in high entropy (disorder).
Solid water (ice): Water molecules are largely immobile, forming a low entropy, regular lattice of hydrogen bonds.
Water as a Solvent
Good solvent for hydrophilic substances: This includes charged and/or polar molecules such as salts, amino acids, carboxylic acids, sugars, some alcohols, and certain liquids and gases.
Dissolving salts: Water disrupts the ionic interactions in salt crystals.
The energy required to break ionic bonds is offset by the favorable increase in entropy as the ordered salt crystal lattice dissolves.
Dissolving proteins: Water molecules can form hydrogen bonds to specific sites on the protein surface.
These surface water molecules help shield charged regions, preventing undesirable interactions with other molecules.
Poor solvent for hydrophobic substances: Nonpolar molecules like alkanes, lipids, and some gases have low solubility in water.
Low Solubility of Hydrophobic Solutes Explained by Entropy
Bulk water: Is highly disordered, possessing high entropy.
Water near a hydrophobic solute: Becomes highly ordered, creating a
Foundations of Biochemistry
Characteristics of Living Matter
High complexity and organization: Living systems are intricately arranged.
Dynamic and coordinated interactions: Individual components interact precisely.
Energy use: Organisms extract, transform, and systematically use energy to build/maintain structures and do work.
Responsiveness: Ability to sense and react to changes in surroundings.
Self-replication: Capacity for precise self-replication while allowing for changes necessary for evolution.
The Cell: Universal Building Block
Basic unit of life: All living organisms are composed of cells.
Diversity: Simplest organisms are single-celled; larger organisms have many cells with specialized functions.
Common features: All cells share traits like a plasma membrane and cytoplasm.
Domains of Life
Organisms are categorized into three domains based on cellular and molecular differences:
Bacteria and Archaea: Unicellular prokaryotes.
Eukarya: Contains four kingdoms:
Protista: Unicellular eukaryotes.
Fungi: Unicellular and/or multicellular eukaryotes.
Plantae: Multicellular eukaryotes.
Animalia: Multicellular eukaryotes.
Molecular Composition and Cell Structures
Cells are built from molecules like sugars, proteins, lipids, and nucleic acids.
Example: Bacterial Cell Structures, Functions, and Compositions
Cell wall: Composed of peptidoglycan (sugar + protein); provides mechanical support.
Cell membrane: Composed of lipid + protein; acts as a permeability barrier.
Nucleoid: Composed of DNA + protein; stores genetic information.
Ribosomes: Composed of RNA + protein; responsible for protein synthesis.
Pili: Composed of protein; involved in adhesion and conjugation.
Flagella: Composed of protein; provides motility.
Cytoplasm: Aqueous solution; main site of metabolism.
Eukaryotic vs. Prokaryotic Cells
Eukaryotic cells are more complex than prokaryotic cells.
Membrane-enclosed organelles: Eukaryotes spatially separate energy-yielding and energy-consuming reactions.
Nucleus: Site of DNA metabolism, protects DNA, selectively imports/exports molecules via nuclear membrane pores.
Mitochondria: Found in animals, plants, and fungi; locations for many energetic reactions.
Chloroplasts: Found in plants; locations for photosynthesis.
Lysosomes: Used for controlled disposal and digestion of un-needed molecules.
Animal vs. Plant Cells
Plant cells have additional structures not found in typical animal cells:
Cell wall: Provides shape, rigidity, and protects from osmotic swelling.
Vacuole: Degrades and recycles macromolecules, stores metabolites.
Chloroplast: Harvests sunlight, produces ATP and carbohydrates.
Glyoxysome: Contains enzymes of the glyoxylate cycle.
Animal cells typically have a Peroxisome (oxidizes fatty acids) and a Lysosome (degrades intracellular debris), which are generally absent in plant cells.
Cytoplasm and Cytosol
Cytoplasm: All material between the plasma membrane and organelle interiors (biomolecules, water, etc.).
Cytosol: The highly viscous aqueous solution filling the cytoplasm where many reactions occur.
Crowded environment: Chemical reaction speeds, limited by diffusion, are slower inside cells than outside due to the crowded nature of the cytosol.
Cytoskeleton
Maintains dynamic cellular organization.
Composed of three protein types:
Microtubules: Provide intracellular transport paths, maintain cell shape, and enable cellular movement.
Actin filaments: Help maintain cell shape, intracellular organization, and allow cellular movement.
Intermediate filaments: Maintain cell shape and intracellular organization.
Chemical Foundations of Life
Essential Elements for Life
Approximately 30 elements are essential for life.
Bulk elements: Atoms present in organic molecules (H, C, N, O, P, S) and some ions (\text{Na}^+, \text{Cl}^-, \text{K}^+, \text{Ca}^{2+}).
Trace elements: Metal ions (e.g., \text{Mg}^{2+}, \text{Zn}^{2+}, \text{Fe}^{2+}) crucial for metabolism.
Unique Role of Carbon
Carbon can form single, double, or triple covalent bonds, leading to a vast diversity of chemical structures.
Different bonding results in various geometrical shapes of molecules.
Carbon Bond Formation and Breaking
Heterolytic cleavage: More common than homolytic cleavage.
Products are ions (e.g., \text{H}^+, \text{H}^-, \text{CH}3^+, \text{CH}3^-) that readily react to form new bonds.
Homolytic cleavage: Products are unstable, highly reactive radicals that can damage other molecules.
Nucleophiles and Electrophiles
Nucleophiles: Atoms with unpaired or extra electrons (\text{ }\textdelta$-$ or $-$ charged atoms); electron-rich species.
Electrophiles: Atoms with electron deficiency (\text{ }\textdelta$+$ or $+$ charged atoms); electron-poor species.
Example of Bond Formation: A carbanion nucleophile reacts with a carbonyl carbon electrophile to form a carbon-carbon bond, generating a new negatively-charged oxygen nucleophile. This oxygen nucleophile can then react with a hydrogen ion (proton) electrophile to form an oxygen-hydrogen bond.
Molecular Structure and Function: Isomers
Isomers: Molecules with the same chemical formula but different arrangements of atoms.
Structural isomers: Have different physical and chemical properties due to distinct bonding arrangements.
Geometric isomers (cis and trans): Have different physical and chemical properties due to restricted rotation around specific bonds leading to different spatial arrangements.
Enantiomers: Non-superimposable mirror images of each other, possessing identical physical and chemical properties (except in chiral environments).
Diastereomers: Non-superimposable structures that are not mirror images of each other, possessing different physical and chemical properties.
Specificity of Biomolecular Interactions
Biomolecular interactions are highly specific.
Typically, only one molecular isomer (e.g., a specific enantiomer) will fit and bind effectively into a specific three-dimensional binding pocket of a protein.
Other isomers lack the correct geometry for effective binding.
Example: Stereoisomers of carvone smell differently because each isomer preferentially binds to distinct protein receptors in olfactory cells.
Common Functional Groups
Functional groups are crucial for molecular reactivity and interactions.
Examples from various biomolecules include:
Carboxyl (COO-): Found in amino acids, fatty acids.
Amino (NH2, NH3+): Found in amino acids, nucleotide bases.
Hydroxyl (OH): Found in sugars, alcohols, serine, threonine, tyrosine.
Thiol (SH): Found in cysteine, glutathione.
Methyl (CH3): Common in many organic molecules, nonpolar.
Carbonyl (C=O): Aldehyde and ketone groups, found in sugars.
Phosphate (PO4^2-): Found in nucleic acids, phospholipids, phosphorylated proteins.
Amido: Peptide bonds, asparagine, glutamine.
Phosphoanhydride: ATP, other nucleotide triphosphates.
Example: Acetyl-coenzyme A contains multiple functional groups: thioester, amido, hydroxyl, phosphoanhydride, phosphoryl, and amino groups.
The Building Blocks of Life
Amino Acids: Contain functional groups vital for protein structure and function.
Nucleic Acids: Composed of nitrogenous bases (A, G, C, T, U), five-carbon sugars (ribose, deoxyribose), and phosphate groups.
Lipids: Include components like glycerol, fatty acids (e.g., palmitate, oleate), and choline.
Sugars: Include simple sugars like \text{ }\textalpha-D-Ribose, \text{2-deoxy- }\textalpha-D-ribose, and \text{ }\textalpha-D-Glucose.
Molecular Hierarchy of Structure
Almost all cellular components are constructed from these fundamental building blocks: nucleic acids, amino acids, sugars, and lipids.
Energy Transductions and Metabolism
Organisms Perform Energy Transductions
Life requires organisms to transform energy from one form to another rapidly enough to sustain biological processes.
Classification by Energy and Carbon Sources
Phototrophs: Obtain energy from sunlight.
Examples: Plants, algae, cyanobacteria, green & purple bacteria.
Chemotrophs: Obtain energy from chemical compounds.
Examples: Animals, fungi, protists, most other bacteria.
Organisms are further classified by their carbon source:
Autotrophs: Use \text{CO}_2 as their primary carbon source.
Photoautotrophs: Use light for energy and \text{CO}_2 for carbon (e.g., plants, algae, cyanobacteria).
Chemoautotrophs: Use chemicals for energy and \text{CO}_2 for carbon (e.g., hydrogen-, sulfur-, iron-, nitrogen-, and carbon monoxide-oxidizing bacteria).
Heterotrophs: Obtain carbon from organic compounds.
Photoheterotrophs: Use light for energy and organic compounds for carbon (e.g., green nonsulfur bacteria, purple nonsulfur bacteria).
Chemoheterotrophs: Use chemicals for energy and organic compounds for carbon (e.g., all animals; most fungi, protists, bacteria).
Chemical Reactions and Energy
Endergonic reactions: Absorb energy from surroundings.
Products have higher energy than reactants.
Change in free energy (\text{ }\textDelta G) is positive (\text{ }\textDelta G > 0).
Example: Synthesis of complex molecules requires energy.
Exergonic reactions: Release energy into surroundings.
Reactants have higher energy than products.
Change in free energy (\text{ }\textDelta G) is negative (\text{ }\textDelta G < 0).
Example: Breakdown of molecules often releases energy.
Thermodynamic Favorability vs. Kinetic Speed
In isolation, endergonic reactions are thermodynamically unfavorable (\text{ }\textDelta G > 0), and exergonic reactions are thermodynamically favorable (\text{ }\textDelta G < 0).
Thermodynamic favorability is distinct from kinetic speed.
Speed of a chemical reaction: Determined by the activation energy (\text{ }\textDelta G^{\text{ }\textddagger}) required to initiate the reaction.
Reactions with large \text{ }\textDelta G^{\text{ }\textddagger} are slower than reactions with small \text{ }\textDelta G^{\text{ }\textddagger} .
Examples of Reaction Energetics and Speed
Hydrolysis of ATP: Favorable and Slow
Removal of phosphoryl and/or phosphoanhydride groups from ATP to form ADP or AMP releases energy, making it favorable (\text{ }\textDelta G < 0).
However, the activation energy (\text{ }\textDelta G^{\text{ }\textddagger}) is large, so the reaction is generally slow without catalysis.
Phosphorylation of Glucose: Unfavorable and Slow
Addition of a phosphate group to glucose requires energy, making it unfavorable (\text{ }\textDelta G > 0).
The activation energy (\text{ }\textDelta G^{\text{ }\textddagger}) is large, so the reaction is generally slow without catalysis.
Energy Coupling: Making Unfavorable Reactions Favorable
Chemical coupling of an endergonic reaction with an exergonic reaction allows otherwise unfavorable reactions to proceed.
The total free energy change (\text{ }\textDelta G) for a coupled reaction is the sum of the individual free energy changes (\text{ }\textDelta G1, \text{ }\textDelta G2).
Example:
Glucose + \text{P}i \longrightarrow Glucose-6-Phosphate + \text{H}2\text{O} (\text{ }\textDelta G^{\text{ }\textdegree}_1 = 14 \text{ kJ/mol} , unfavorable)
ATP + \text{H}2\text{O} \longrightarrow ADP + \text{P}i (\text{ }\textDelta G^{\text{ }\textdegree}_2 = -30 \text{ kJ/mol} , favorable)
Coupled: Glucose + ATP \longrightarrow Glucose-6-Phosphate + ADP (\text{ }\textDelta G^{\text{ }\textdegree} = \text{ }\textDelta G^{\text{ }\textdegree}1 + \text{ }\textDelta G^{\text{ }\textdegree}2 = -16 \text{ kJ/mol} , overall favorable)
Increasing Chemical Reaction Speed
Temperature increase: Raises energy in the environment, speeding up reactions. Not practical for living organisms due to macromolecule stability limits.
Reducing activation energy: This is the effective method in living organisms.
Catalysts (e.g., enzymes) are used to lower the activation energy barrier (\text{ }\textDelta G^{\text{ }\textddagger}).
Catalysis: Lowering Activation Energy
A catalyst increases the rate of a chemical reaction without being consumed.
Catalysts lower the activation energy (\text{ }\textDelta G^{\text{ }\textddagger}) but do not alter the total free energy change (\text{ }\textDelta G) of the reaction.
Enzymes are biological catalysts, typically proteins, characterized by:
Acceleration under mild conditions (physiological temperature, pH).
High specificity for their substrates.
Regulation of their activity.
Metabolism
Metabolism: The entire set of chemical reactions occurring in a cell.
Catabolic reaction pathways: Break down complex molecules (e.g., degradation of carbohydrates, lipids, amino acids).
These pathways are generally exergonic (release energy).
Anabolic reaction pathways: Synthesize complex molecules from simpler ones (e.g., synthesis of carbohydrates, lipids, amino acids).
These pathways are generally endergonic (require energy input).
Metabolism is tightly regulated through various processes to maintain cellular homeostasis.
Genetic and Evolutionary Foundations
Origin of Life
Earth formed approximately 4.5 billion years ago.
Life originated about 0.7 billion years later, roughly 3.8 billion years ago.
Miller-Urey experiment: Demonstrated that some essential molecules for life (e.g., aldehydes, amino acids) could form under abiotic conditions from early atmospheric components.
Abiotic Assembly of Complex Molecules
Simple molecules can self-assemble abiotically into more complex structures such as lipids, nucleic acids, and peptides.
These more complex molecules could then organize into early living systems.
RNA World Hypothesis
The ability to pass on genetic information was crucial for the continuation of life.
Hypothesis: RNA was the original genetic material.
Dual function: RNA could act both as an information carrier (like DNA) and as a biocatalyst (like proteins) for its own replication.
Ribozymes: RNA molecules with catalytic activity, supporting the idea of RNA as an early biocatalyst.
Transition to DNA
While RNA still encodes information and catalyzes some reactions, DNA is now the primary genetic material for most organisms due to its increased stability.
Reasons for DNA's stability over RNA:
Deoxyribose sugar: Contains one less oxygen atom than ribose (in RNA), preventing easy hydrolysis of phosphodiester linkages, which can readily occur in RNA.
Double-stranded nature: DNA typically forms a double helix, providing greater stability compared to the generally single-stranded RNA.
Specific hydrogen bonding: Precise base-pairing between nucleobases in DNA allows for more accurate replication, making DNA a more suitable and reliable genetic material.
RNA's Role in Gene Expression
Genetic information stored in DNA is copied into an RNA form (mRNA) through transcription.
This RNA then carries the instructions for making proteins, a process called translation, which occurs on ribosomes.
Proteins are the key functional molecules responsible for the vast majority of cellular processes.
Genetic Diversity and Evolution
Random mutations in DNA: Generate genetic diversity within organisms, leading to new traits.
Natural selection: Mutations that confer a survival or reproductive advantage in a particular environment are more likely to be passed on to offspring.
Example: Duplication and subsequent mutation of the hexokinase gene led to a similar protein capable of metabolizing a different sugar, providing an evolutionary advantage.
Evolution of Eukaryotes through Endosymbiosis
Early eukaryotic cells acquired energy-processing organelles, mitochondria and chloroplasts, by engulfing bacteria.
These engulfed bacteria were retained within the host cell, forming a symbiotic relationship and paving the way for eukaryotic cellular complexity.
Water, the Solvent of Life
Water: The Medium for Life
Ubiquity: Organisms typically consist of 70-90\% water.
Aqueous reactions: Most biochemical reactions occur in an aqueous environment.
Structural determinant: Water is critical for the structure and function of proteins, nucleic acids, and membranes.
Protection: Water absorbs and reflects UV light, shielding organisms from damaging electromagnetic radiation.
Structure of the Water Molecule
Geometry: A distorted tetrahedron with four sp^3 orbitals around the oxygen atom.
Two electron pairs form covalent bonds with two hydrogen atoms.
Two electron pairs are nonbonding (lone pairs).
Electronegativity: The oxygen atom is highly electronegative, leading to a net dipole moment (a noncovalent interaction).
Hydrogen bonding: Water can act as both a hydrogen bond donor (via H atoms) and a hydrogen bond acceptor (via O atom lone pairs).
Hydrogen Bonds: A Type of Dipole-Dipole Interaction
Dipole interactions: Electrostatic interactions between uncharged polar molecules.
Hydrogen bonds: Specific dipole-dipole interactions occurring between:
A hydrogen donor: A hydrogen atom covalently bonded to a highly electronegative atom (e.g., -OH and -NH functional groups).
A hydrogen acceptor: An electronegative atom with a lone pair of electrons (e.g., R-O-R, C=O, and R-N=R functional groups).
Strength of hydrogen bonds: Influenced by geometry and distance.
Orientation: Strongest when the three atoms involved are collinear, maximizing electrostatic interaction.
Distance: Strongest within an optimal range of 0.18 - 2.2 \text{ nm} . Strong interactions occur when atoms are closer (e.g., 0.18 \text{ nm}), weakening as distance increases.
Other Types of Noncovalent Interactions
Ionic interactions (salt bridges): Electrostatic interactions between permanently charged atoms or molecules, or between an ion and a permanent dipole.
Hydrophobic effect: Associated with minimizing the structural order of water molecules around nonpolar substances. It is not an attractive force between hydrophobic molecules, but rather an indirect effect driven by the increase in water entropy.
Van der Waals interactions (London dispersion forces): Weak, transient interactions occurring between any two atoms that are close to each other.
Random variations in electron positions create temporary dipoles that weakly attract each other (typically at 0.4 - 0.7 \text{ nm} apart).
The van der Waals radius of an atom defines how close it can approach another atom (typically < 0.2 \text{ nm}) before electron cloud repulsion occurs.
Additive Strength of Weak Interactions
Individually weak interactions become very strong when they are numerous and added together.
Example: Gecko feet adhesion:
Gecko feet have cellular extensions (setae and spatulae) made of keratin protein.
Each spatulae makes atomic-scale contact with a surface, generating attachment energy through van der Waals interactions.
With approximately 1 billion spatulae, the combined van der Waals forces are immense, supporting over 100 \text{ kg} of weight (more than 1000 times the gecko's own weight).
Cooperative Hydrogen Bonding in Water
Each water molecule can form up to four hydrogen bonds, which accounts for water's unique properties.
Unique properties:
High melting point and boiling point relative to its small molecular mass.
Unusually large surface tension.
Ice vs. Liquid Water:
Ice: Contains more hydrogen bonds per water molecule, forming a regular, open lattice structure. This leads to ice having a lower density than liquid water.
Liquid water: Water molecules move freely, and hydrogen bonds constantly break and reform, resulting in high entropy (disorder).
Solid water (ice): Water molecules are largely immobile, forming a low entropy, regular lattice of hydrogen bonds.
Water as a Solvent
Good solvent for hydrophilic substances: This includes charged and/or polar molecules such as salts, amino acids, carboxylic acids, sugars, some alcohols, and certain liquids and gases.
Dissolving salts: Water disrupts the ionic interactions in salt crystals.
The energy required to break ionic bonds is offset by the favorable increase in entropy as the ordered salt crystal lattice dissolves.
Dissolving proteins: Water molecules can form hydrogen bonds to specific sites on the protein surface.
These surface water molecules help shield charged regions, preventing undesirable interactions with other molecules.
Poor solvent for hydrophobic substances: Nonpolar molecules like alkanes, lipids, and some gases have low solubility in water.
Low Solubility of Hydrophobic Solutes Explained by Entropy
Bulk water: Is highly disordered, possessing high entropy.
Water near a hydrophobic solute: Becomes highly ordered, creating a decrease in entropy locally. The overall process becomes spontaneous only if the nonpolar molecules cluster together, reducing the total surface area exposed to water and thus minimizing the number of ordered water molecules. This increases the entropy of the bulk water.
Ionization of Water, Weak Acids, and Weak Bases
Water's ionization: Water undergoes slight but significant ionization, acting as both a weak acid and a weak base.
\text{H}_2\text{O} \rightleftharpoons \text{H}^+ + \text{OH}^- (Simplified)
In reality: \text{2H}2\text{O} \rightleftharpoons \text{H}3\text{O}^+ + \text{OH}^- (Hydronium and Hydroxide ions)
Equilibrium constant (K{\text{eq}}) for water: The product of the concentrations of \text{H}^+ and \text{OH}^- ions is constant in pure water at 25^{\circ}\text{C}. \text{K}{w} = [\text{H}^+][\text{OH}^-] = 1.0 \times 10^{-14} \text{ M}^2 .
pH scale: A convenient way to express hydrogen ion concentration.
\text{pH} = -\text{log}[\text{H}^+]
Neutral pH at 25^{\circ}\text{C} is 7.0 where [\text{H}^+] = [\text{OH}^-] = 1.0 \times 10^{-7} \text{ M} .
Weak Acids and Bases
Weak acids: Partially dissociate to yield a proton and a conjugate base (\text{HA} \rightleftharpoons \text{H}^+ + \text{A}^-).
Weak bases: Partially associate with a proton to form a conjugate acid (\text{B} + \text{H}^+ \rightleftharpoons \text{BH}^+).
Acid dissociation constant (K_a): Measures the strength of a weak acid.
\text{K}_a = \frac{[\text{H}^+][\text{A}^-]}{[\text{HA}]}
pKa: A more convenient way to express Ka .
\text{p}Ka = -\text{log }Ka
A lower pK_a indicates a stronger acid.
Buffers
Definition: Aqueous systems that resist changes in pH upon the addition of small amounts of acid or base.
Composition: Typically consist of a weak acid and its conjugate base, or a weak base and its conjugate acid.
Buffering capacity: Most effective when the pH is close to the pKa of the weak acid component (within \pm 1 pH unit of the pKa).
Henderson-Hasselbalch equation: Relates pH, pK_a, and the ratio of conjugate base to weak acid concentrations.
\text{pH} = \text{p}K_a + \text{log}\frac{[\text{A}^-]}{[\text{HA}]}
Biological Buffering Systems
Phosphate buffer system: Important in intracellular fluid (\text{H}2\text{PO}4^- / \text{HPO}4^{2-}), with a pKa of 6.86. Effective near physiological pH.
Bicarbonate buffer system: Crucial for maintaining blood pH (\text{H}2\text{CO}3 / \text{HCO}3^-). Involves carbonic anhydrase and the equilibrium between dissolved \text{CO}2 and carbonic acid. This open system is particularly powerful because \text{CO}_2 can be expelled or retained by the lungs.
Proteins: Amino acid side chains (e.g., histidine imidazole group) act as weak acids/bases, contributing significantly to buffering capacity in cells and blood.
Acid-Base Balance in Blood
Normal blood pH: Tightly maintained between 7.35 and 7.45.
Acidosis: Blood pH below 7.35. Can be caused by metabolic issues (e.g., diabetic ketoacidosis) or respiratory problems (e.g., hypoventilation leading to \text{CO}_2 buildup).
Alkalosis: Blood pH above 7.45. Can be caused by metabolic issues (e.g., severe vomiting) or respiratory problems (e.g., hyperventilation leading to excessive \text{CO}_2 loss).
Regulation: The body uses the bicarbonate buffer system, respiratory compensation (altering \text{CO}2 exhalation), and renal compensation (excreting or reabsorbing \text{H}^+ and \text{HCO}3^- ) to maintain proper pH.