Foundations of BioChemistry

Living organisms are distinguished by:

1. High degree of chemical complexity and microscopic organization
2. Systems for extracting, transforming, and using energy from the environment
3. Capacity for precise self-replication and self-assembly
4. Mechanisms for sensing and responding to environmental changes
5. Defined functions for components with regulated interactions among them
6. History of evolutionary change

Unlike inanimate matter, which tends to decay toward disorder and equilibrium with surroundings, living systems maintain and increase their organization.

• Lithotrophs:

  • Obtain energy from inorganic chemical compounds
  • Examples include sulfur bacteria (oxidize sulfur compounds) and hydrogen bacteria
  • Still require organic carbon sources (are heterotrophic)
  • Often found in extreme environments where inorganic energy sources are abundant

• Organotrophs:

  • Obtain energy from organic chemical compounds
  • Examples include most prokaryotes and all non-photosynthetic eukaryotes (including humans)
  • Are heterotrophic (require organic carbon sources)
  • Most common metabolic strategy for animals, fungi, and many bacteria

Animal Cells: Mitochondria only

• Mechanism: Oxidizes organic fuels (pyruvate, fatty acids) via Krebs cycle and electron transport chain
• Output: ATP through oxidative phosphorylation
• Efficiency: Higher ATP yield per glucose (30-32 ATP)
• Location: Throughout cytoplasm
• Origin: Endosymbiotic relationship with ancient proteobacteria

Plant Cells: Both mitochondria and chloroplasts

• Mitochondria: Same as animal cells
• Chloroplasts:
  • Mechanism: Captures light energy in thylakoids; fixes CO₂ in stroma
  • Output: ATP through photophosphorylation; NADPH; carbohydrates
  • Unique structures: Thylakoid membranes, grana, stroma
  • Origin: Endosymbiotic relationship with ancient cyanobacteria

Functional Integration in Plants:

• Chloroplasts produce carbohydrates that can fuel mitochondrial respiration
• Plants can generate ATP in both light (photosynthesis) and dark (respiration)
• Specialized metabolic pathways like photorespiration involve both organelles

Example: During daytime, leaf cells primarily use chloroplast-generated ATP, while at night they rely on mitochondrial ATP production from stored carbohydrates.

Cellular structural hierarchy consists of four levels:

Level 1: Monomeric units

• Simple subunits like amino acids, nucleotides, and sugars
• Small molecules with specific functional groups

Level 2: Macromolecules

• Polymers formed from monomers by covalent bonds
• Examples: proteins, DNA, polysaccharides
• Information-rich structures (especially proteins and nucleic acids)

Level 3: Supramolecular complexes

• Assemblies of macromolecules held by noncovalent interactions
• Examples: chromosomes, plasma membranes, ribosomes
• Specific three-dimensional arrangements

Level 4: Cells and organelles

• Complete functional units
• Compartmentalized structures with specific functions
• Integrated systems of supramolecular complexes

This hierarchy demonstrates how biological complexity emerges from simple building blocks through specific interactions.

Physicochemical factors determining binding specificity and strength:

1. Geometric complementarity: • Precise shape matching between binding pocket and ligand • Steric exclusion of incorrectly shaped molecules

2. Electrostatic interactions: • Attraction between opposite charges (e.g., positively charged arginine and negatively charged RNA phosphates) • Repulsion between like charges preventing non-specific binding

3. Hydrogen bonding networks: • Specific donor-acceptor patterns requiring precise alignment • Contribution to binding energy and directionality

4. Hydrophobic effects: • Exclusion of water from non-polar interfaces • Entropic driving force for binding

5. Van der Waals forces: • Short-range attractions optimized by close molecular packing • Requires precise spatial arrangement of atoms

Together, these interactions create binding sites with exquisite specificity that can distinguish between even closely related molecules, enabling precise molecular recognition essential for biological function.

The three primary inputs to cellular metabolism are:

1. Stored nutrients
2. Ingested foods
3. Solar photons (for photosynthetic organisms)

Their transformation through metabolic pathways:

• These inputs enter catabolic (exergonic) reaction pathways
• Catabolic processes break them down, releasing energy that is captured as ATP
• The breakdown produces simple molecules (CO₂, NH₃, H₂O) as end products
• These simple molecules serve as precursors that can be incorporated into anabolic pathways
• Anabolic (endergonic) pathways use ATP energy to transform these precursors into:
  • Complex biomolecules (proteins, nucleic acids, polysaccharides, lipids)
  • Cellular work (mechanical, osmotic, other)

This transformation represents a continuous cycle where matter flows between complex and simple forms, while energy flows from energy-rich sources through ATP to energy-requiring processes.

Example: Glucose from food is catabolized via glycolysis and the TCA cycle to CO₂ and H₂O, generating ATP, which powers the anabolic synthesis of glycogen from glucose precursors.

The antiparallel orientation of DNA strands (one 5'→3', the other 3'→5') is significant because:

For replication:

• Allows simultaneous synthesis of both strands despite DNA polymerase only working in 5'→3' direction
• Creates leading strand (continuous synthesis) and lagging strand (discontinuous Okazaki fragments)
• Enables coordinated replication through the replication fork structure

For transcription:

• Provides directionality for RNA polymerase binding and synthesis
• Ensures only one strand (template strand) is transcribed in any gene region
• Creates defined start and stop sites for gene expression

For genetic stability:

• Creates structural constraints that prevent certain types of mutations
• Provides redundancy—information exists on both strands
• Facilitates repair mechanisms that use the complementary strand as reference
• Maintains topological integrity during DNA manipulation

Example: When DNA damage occurs on one strand, repair enzymes can use the undamaged complementary strand as a template to restore the original sequence, preserving genetic information.

The coevolution of RNA and protein represents a critical transition because:

1. Functional shift:

   • RNA initially served dual roles as both genetic material and catalyst
   • Peptides began supporting RNA replication, creating a partnership
   • This partnership allowed specialization of molecular roles

2. Emergence of feedback loops:

   • RNA could catalyze peptide synthesis
   • These peptides could then enhance RNA replication
   • Created mutual dependency and evolutionary advantage

3. System complexity increase:

   • Allowed for development of more complex catalytic functions
   • Enabled more efficient and accurate replication systems
   • Set the stage for the later development of translation machinery

This transition point established the fundamental molecular collaboration that became the foundation for all complex cellular life, where nucleic acids and proteins work together in complementary roles.

• Step 1: Calculate cell volume Volume = (4/3)πr³ = (4/3)π(25 μm)³ = 65,450 μm³

• Step 2: Convert to compatible units Cell volume = 65,450 μm³ = 6.545 × 10¹⁶ nm³

• Step 3: Calculate volume of one actin molecule Volume = (4/3)π(1.8 nm)³ = 24.43 nm³

• Step 4: Calculate theoretical number of actin molecules Number = 6.545 × 10¹⁶ nm³ ÷ 24.43 nm³ = 2.68 × 10¹⁵ molecules

• Significance:

  • This represents theoretical maximum capacity, not actual content
  • Actual cells contain diverse macromolecules and organelles
  • Actin exists as organized filaments, not individual molecules
  • Demonstrates the enormous number of protein molecules in cells
  • Highlights the complex spatial organization required in functioning cells

The eukaryotic cytoskeleton consists of three distinct filament types that differ in size, composition, organization, and function:

1. Actin Filaments (Microfilaments)

   • Structure: Thinnest filaments (6-8 nm diameter)
   • Composition: Polymerized actin monomers
   • Organization: Form parallel bundles/stress fibers; dynamic networks anchored to cell membrane
   • Functions:
     • Maintain cell shape and cortical integrity
     • Enable cell motility and contraction
     • Participate in cytokinesis and endocytosis
     • Provide tensile strength

2. Microtubules

   • Structure: Thickest, hollow cylindrical filaments (22-25 nm diameter)
   • Composition: α and β tubulin dimers
   • Organization: Typically radiate from centrosome (cell center); highly dynamic
   • Functions:
     • Determine cell shape and polarity
     • Serve as tracks for organelle/vesicle transport
     • Form mitotic spindle during cell division
     • Support intracellular trafficking

3. Intermediate Filaments

   • Structure: Medium-sized filaments (8-12 nm diameter)
   • Composition: Various fibrous proteins (keratins, vimentin, lamins, etc.)
   • Organization: Form extensive meshworks throughout cytoplasm
   • Functions:
     • Provide mechanical strength and stability
     • Resist shear stress and tension
     • Anchor organelles
     • Most stable of the three filament types

Common characteristic: All three undergo regulated assembly/disassembly and have their locations and functions controlled by accessory proteins that can link filaments to each other or facilitate organelle movement along them.