Cellular Foundations

What Makes Organisms Living

Biochemistry explains life by examining the structures, interactions, and reactions of molecules. Living systems are characterized by organization, metabolism, growth, responses to stimuli, homeostasis, reproduction, and evolutionary adaptation.

• Homeostasis: Regulation of internal conditions, not a static state.

• Metabolism: The network of chemical reactions in a cell, divided into:

  • Catabolism: Breakdown of fuels to capture energy.

  • Anabolism: Use of energy and small precursors to build larger molecules.

• Adaptation: Occurs across generations via evolution, not by individual response alone.

Universal Cellular Features

• Plasma Membrane: Flexible lipid-protein boundary; hydrophobic interior restricts ions and polar molecules; contains transporters, receptors, and catalytic proteins.

• Cytoplasm: Contents inside the plasma membrane (excluding the nucleus in eukaryotes); includes cytosol (aqueous phase with enzymes, metabolites, RNA, cofactors, ions).

• Genetic Material & Ribosomes: DNA stores instructions; ribosomes synthesize proteins; DNA is housed in a nucleus (eukaryotes) or nucleoid (prokaryotes).

Domains and Cell Types

Note: Archaea and Eukarya are more closely related to each other than to Bacteria. The six-kingdom scheme (Archaea, Bacteria, Protista, Fungi, Plantae, Animalia) is also used for classification.

Cell Envelopes and Organelles

• Bacterial Cell Envelope: Includes plasma membrane and external layers.

  • Gram-positive: Thick peptidoglycan, no outer membrane.

  • Gram-negative: Thin peptidoglycan, outer membrane with lipopolysaccharide and porins.

  • Archaea: Distinct envelope chemistry, may include protein layers or other polymers.

• Other Structures: Plasmids (extra DNA), pili (attachment), flagella (movement).

Cell Size, Organization, and Laboratory Methods

• Surface Area/Volume Ratio: Limits cell size; as radius increases, SA/V decreases ( for spheres).

• Structural Hierarchy:

  • Small subunits (amino acids, nucleotides) → Macromolecules (proteins, DNA) → Supramolecular complexes (ribosomes, membranes) → Organelles/cells.

• Weak Interactions: Hydrogen bonds, ionic attractions, van der Waals, hydrophobic effect stabilize assemblies.

• Cell Fractionation: Homogenize cells, centrifuge to separate components by size/density; pellet = sediment, supernatant = liquid above. Enrichment ≠ purity.

• In vitro vs. In vivo: In vitro = outside living system; in vivo = within living system. Purification can alter behavior by removing partners/regulation.

Chemical Foundations

Elements and Carbon

• Major Elements: C, H, O, N (most abundant); P, S, and ions (Na+, K+, Ca2+, Mg2+) are also important.

• Trace Elements: Essential in small amounts (e.g., Fe in hemoglobin).

• Carbon: Four valence electrons, forms stable chains, branches, rings; tetrahedral geometry (109.5°), double bonds are planar (120°).

Major Biomolecules

Note: Lipids are not generally polymers; they assemble noncovalently.

Cell Composition and Molecular Collections

• E. coli Example: Water 70%, proteins 15%, RNA 6%, polysaccharides 3%, lipids 2%, small molecules 2%, DNA 1%, ions 1% (by weight).

• Omics: Genome (DNA), proteome (proteins), metabolome (small molecules), glycome (carbohydrates), lipidome (lipids).

• Primary vs. Secondary Metabolites: Primary = central pathways; secondary = specialized roles (e.g., caffeine, morphine).

Functional Groups to Recognize

Example: Acetyl-CoA contains an acetyl group attached via a thioester to coenzyme A.

Stereochemistry and Molecular Recognition

• Configuration: Fixed spatial arrangement; requires breaking covalent bonds to change (e.g., cis/trans isomers).

• Conformation: Changeable by rotation around single bonds (e.g., staggered/eclipsed ethane).

• Stereoisomers: Same formula/connectivity, different spatial arrangement.

• Enantiomers: Nonsuperimposable mirror images (one chiral carbon = two enantiomers).

• Diastereomers: Stereoisomers not mirror images (multiple chiral centers).

• Chiral Carbon: Tetrahedral carbon with four different substituents.

• R/S System: Assign priorities, lowest group away; clockwise = R, counterclockwise = S.

• D/L System: Relative configuration; does not indicate optical rotation sign.

• Racemic Mixture: Equal enantiomers; no net optical rotation.

• Stereospecificity: Enzymes/receptors recognize specific 3D arrangements; only certain isomers are biologically active.

Physical Foundations

Energy Flow and Systems

• System Types:

  • Open: Exchanges matter and energy (cells).

  • Closed: Exchanges energy, not matter.

  • Isolated: Exchanges neither.

• First Law: Energy is conserved.

• Second Law: Total entropy increases in spontaneous processes; cells maintain order by exporting entropy.

Sources of Energy and Carbon

• Phototrophs: Use light for energy.

• Chemotrophs: Use chemical fuels.

• Autotrophs: Use CO2 as carbon source.

• Heterotrophs: Require organic carbon.

• Oxidation/Reduction: Oxidation = loss of electrons; reduction = gain of electrons.

Example: Humans are chemoheterotrophs; cyanobacteria are photoautotrophs.

Gibbs Free Energy

• Equation:

• Interpretation:

  • Negative : Exergonic, favorable.

  • Positive : Endergonic, requires coupling.

  • : Equilibrium.

• Spontaneous: Thermodynamically favorable, not necessarily fast.

Equilibrium and Energy Calculations

• Reaction:

• Reaction Quotient:

• Equilibrium Constant: (when )

• Free Energy Relationships:

• Gas Constant: J mol−1 K−1 = 0.008314 kJ mol−1 K−1

• Biochemical Standard State: (usually pH 7)

ATP, Enzymes, and Metabolic Control

• ATP: Adenine, ribose, three phosphates; hydrolysis is highly exergonic; supports synthesis, transport, movement.

• Dynamic Steady State: Concentrations remain constant due to balanced production/consumption, not equilibrium.

• Enzymes: Lower activation energy (), accelerate reactions, do not change or .

• Metabolism:

  • Catabolism: Degrades fuels, captures energy in ATP/NADH.

  • Anabolism: Builds molecules using ATP/NADPH.

  • Feedback inhibition: End product inhibits earlier enzyme.

  • Gene regulation: Alters enzyme amounts.

Genetic Foundations

DNA Structure and Function

• DNA: Polymer of deoxyribonucleotides; stores sequence information; double helix is complementary and antiparallel (A–T, G–C pairing).

• Replication: Semiconservative; each daughter helix has one old and one new strand.

• Information Flow: DNA → RNA (transcription) → Protein (translation) → Folding/assembly → Function.

• Protein Folding: Sequence determines structure; noncovalent interactions stabilize conformation; chaperones may assist.

Evolutionary Foundations

Variation, Inheritance, and Selection

• Mutation: Change in genetic sequence; can be harmful, beneficial, or neutral.

• Selection: Alters frequency of heritable variants based on survival/reproduction.

• Gene Duplication: Extra gene copy can evolve new function while original retains old function.

• Evidence for Common Ancestry: Shared biomolecules, genetic systems, and metabolic pathways; sequence similarity infers homology.

Origin of Life and Endosymbiosis

• Chemical Evolution: Abiotic formation of building blocks (e.g., Miller–Urey experiment).

• RNA World Hypothesis: RNA as both information carrier and catalyst; plausible early genetic system.

• Endosymbiosis: Mitochondria from aerobic bacteria; chloroplasts from cyanobacteria; permanent integration into host cells.

Applications and Experimental Reasoning

Connecting Structure to Function

• Examples: Coronavirus (molecular recognition), amyloid fibrils (protein aggregation), hemophilia (clotting protein), sickle-cell anemia (hemoglobin mutation).

• Experimental Analysis: Identify question, variable, outcome, control; distinguish observation from conclusion; normalize data for fair comparison.

Common Misconceptions

• Anabolism builds molecules (uses energy); catabolism breaks down fuels (captures energy).

• Cellular order does not violate the second law; total entropy (system + surroundings) increases.

• Constant concentration ≠ equilibrium; could be dynamic steady state.

• Enzymes lower activation energy, not .

• Actual depends on and temperature, not just .

• Peroxisomes are in both plants and animals.

• Stereoisomers can have different biological effects.

• Mutations can be neutral, harmful, or beneficial.

Practice and Problem Solving

Sample Calculations and Data Analysis

• Surface Area/Volume: for spheres; smaller cells have higher SA/V.

• Number of Molecules: Use cell volume, concentration, and Avogadro's number.

• Free Energy: ; convert units as needed.

• Equilibrium: ; .

• Stereoisomers: Maximum number = (n = chiral centers).

• DNA Length: Number of base pairs × 0.34 nm per pair.

Experimental Data Interpretation

• Compare activities in cell fractions; normalize to protein content for specificity.

• Assess pH and metal ion dependence for enzyme activity; not all ions or concentrations are equally effective.

• Interpret nucleotide requirements in biosynthetic assays; impurities can affect results.

• Distinguish heritable resistance from temporary adaptation by testing descendants after several generations.

Final Self-Check

• Explain the five foundations of biochemistry.

• Identify major functional groups in biomolecules.

• Solve problems involving and cell size.

• Connect a mutation to changes in protein structure and function.

Additional info: This guide is based on Chapter 1 of a biochemistry textbook and is intended as a comprehensive review of foundational concepts, including practice questions and answers for exam preparation.