Chapter 1: Foundations of Biochemistry – Vocabulary Flashcards

1.1 Cellular Foundations

• Biochemistry describes the structures, mechanisms, and chemical processes shared by all organisms, expressed as the molecular logic of life. It connects cellular, chemical, physical (thermodynamic), and genetic backgrounds to lifetime properties and evolution.
• Core idea: all cells—simple to complex—share unity and diversity at the biochemical level; the membrane defines the cell boundary and controls exchange with surroundings; cytoplasm (cytosol) contains enzymes, nucleotides, metabolites, coenzymes, inorganic ions, ribosomes; genetic material is stored as DNA in a nucleus (eukaryotes) or a nucleoid (bacteria).
• Plasma membrane: tough, flexible lipid bilayer; selectively permeable; transport/receptor/enzymatic proteins embedded in it; growth and division involve insertion of new lipids/proteins; membrane integrity maintained during fission.
• Cytoplasm vs cytosol: cytosol is a dense aqueous solution with enzymes, RNAs, substrates, and metabolites; organelles suspended within cytosol.
• Nucleus vs nucleoid: nucleus is a membrane-bounded compartment containing chromatin; nucleoid is a non-membrane region containing the genome in bacteria.
• Eukaryotes vs prokaryotes:
  • Eukaryotes: nucleus surrounded by nuclear envelope; membrane-bound organelles (mitochondria, ER, Golgi, lysosomes; chloroplasts in plants/algae); larger cells.
  • Prokaryotes: no nuclear membrane; DNA is in a nucleoid; often have an outer protective envelope and a cell wall with peptidoglycan; archaea differ in membrane lipids and peptidoglycan-like structures.
• Cellular dimensions and diffusion limits:
  • Most cells are microscopic: animal/plant cells ~5–100 μm; many bacteria ~1–2 μm.
  • Diffusion limits set a practical upper size; mycoplasmas ~300 nm in diameter; a single bacterial ribosome ~20 nm; surface-to-volume ratio decreases as cells grow, potentially limiting O2 diffusion and metabolism beyond certain sizes.
• Three domains of life (phylogeny): Archaea, Bacteria (Eubacteria), and Eukarya. Archaea and Bacteria are prokaryotes; Eukarya are eukaryotes. Archaea are often more closely related to eukaryotes than to bacteria; all domains share a common evolutionary origin.
• Energy and ecological strategies (Fig. 1–5):
  • Phototrophs trap and use sunlight; chemotrophs derive energy from oxidation of chemical fuels.
  • Autotrophs fix CO2 as carbon source; heterotrophs require organic nutrients.
  • Lithotrophs oxidize inorganic compounds; organotrophs oxidize organic compounds.
  • No chemotroph is autotroph (cannot fix CO2 as sole carbon source); phototrophs may be autotrophs or heterotrophs depending on carbon source.
  • E. coli as an example: chemoorganoheterotroph (organic carbon, organic energy source). Cyanobacteria: photolithoautotroph (light energy, CO2 as carbon source).
• E. coli and bacterial cell structure (Fig. 1–6): outer membrane, inner plasma membrane, periplasmic space; peptidoglycan layer; ribosomes ~15,000 per cell; nucleoid with a single circular DNA; plasmids can carry toxin/antibiotic resistance and can be manipulated in the lab.
• Eukaryotic cells (Fig. 1–7): larger cells; nucleus; organelles (mitochondria, ER, Golgi, lysosomes); plant cells add vacuoles and chloroplasts; cytoskeleton provides structure and transport scaffolding.
• Cell fractionation and subcellular localization (Fig. 1–8): differential centrifugation separates organelles by size/sedimentation; isopycnic (density-gradient) centrifugation separates by buoyant density; examples include lysosome, mitochondrion, ER fragments purified via gradient
• Cytoskeleton and organelle dynamics (Fig. 1–9): three filament types—actin filaments, microtubules, intermediate filaments; dynamic assembly/disassembly; motor proteins move organelles along filaments; endomembrane system organizes metabolism; exocytosis/endocytosis enable trafficking between cytoplasm and surroundings.
• Macromolecules and supramolecular structures (Fig. 1–10, 1–11): polymeric macromolecules (proteins, nucleic acids, polysaccharides, lipids) built from monomers; macromolecules interact via noncovalent forces to form supramolecular assemblies; three-dimensional structure (configuration and conformation) govern function; configurational isomers (stereoisomers) cannot interconvert without breaking bonds; conformational isomers arise from rotation about single bonds.
• Noncovalent interactions and stability (Table 1–1): hydrogen bonds, ionic interactions, hydrophobic interactions, van der Waals; collectively stabilize supramolecular assemblies; energies of noncovalent interactions are smaller on average than covalent bonds.
• In vitro vs in vivo: purified components studied in vitro may miss interactions present in cells; amy environment and macromolecular crowding influence enzyme activity and complex formation; cellular organization is essential for proper function.
• Summary 1.1 (highlights): all cells share bounded plasma membranes, cytosol/metabolites, and a genome; energy-coupling via redox chemistry; eukaryotic cells compartmentalize processes; cytoskeleton and endomembrane system organize metabolism; supramolecular complexes rely on noncovalent interactions; in vitro studies can miss in vivo interactions.

1.2 Chemical Foundations

• Central goal: explain biological form and function in chemical terms; universal chemical features across life indicate common origins and shared chemistry.
• Elements and biochemistry:
  • Only about 30 of the ≈90 naturally occurring elements are essential; light elements (Z ≤ 34) dominate in living matter.
  • The four most abundant elements by atom percentage in organisms: hydrogen, oxygen, nitrogen, carbon; together >99% of the mass of most cells.
  • Trace elements (e.g., Fe, Zn, Cu) are essential for protein function (enzymes, cofactors). Example: four iron ions in hemoglobin are essential for oxygen transport.
• Biomolecules are carbon-based with diverse functional groups:
  • Carbon’s versatility enables carbon–carbon single, double, and triple bonds; tetrahedral geometry around sp3 carbon (109.5°) and planarity around sp2/sp; rotation around single bonds is possible; double bonds restrict rotation; covalent bonds form skeletons; functional groups determine chemical reactivity (Fig. 1–13, 1–14).
  • Carbon allows linear, branched, and cyclic structures; functional groups confer characteristic chemistry: alcohols (–OH), carbonyls (aldehydes/ketones), carboxylic acids (–COOH), esters, ethers, sulfides, phosphates, amines, amides, imidazole, guanidino groups, phosphate groups, etc. (Fig. 1–15, 1–16).
  • Many biomolecules are polyfunctional (contain two or more different functional groups).
• Monomeric subunits and macromolecules:
  • Proteins: polymers of amino acids; major fraction of cell mass besides water; catalysts (enzymes) and structural roles.
  • Nucleic acids: DNA and RNA; store and transmit genetic information; some RNA have catalytic or structural roles in complexes.
  • Polysaccharides: energy stores (starch, glycogen) and extracellular structural elements;
    oligosaccharides on proteins/lipids at cell surface serve as signals.
  • Lipids: membranes, energy stores, pigments, intracellular signals; not macromolecules by themselves but form large noncovalent assemblies in membranes.
• Universal small-molecule metabolome:
  • A core set of 100–200 metabolites in cytosol; include amino acids, nucleotides, sugars, phosphorylated derivatives, and various acids; concentrations range from μM to mM; membrane impermeability protects this cytosolic pool; transporters can import/export some molecules (Box 1–1 on molecular weights).
• Macromolecular architecture and structure:
  • Macromolecules (proteins, nucleic acids) are informational polymers with sequence-defined structures; three-dimensional structure is stabilized by noncovalent interactions; folding processes aided by molecular chaperones; folding yields native conformation essential for function; proteins can assemble into larger supramolecular complexes.
• Structural representation and stereochemistry (Figs. 1–11, 1–18, 1–19, 1–20):
  • Configurational isomers (R/S) are fixed by the arrangement around chiral centers or double bonds; D/L convention used for sugars/amino acids; RS system more general for complex biomolecules.
  • Conformation: spatial arrangement around single bonds; conformers can interconvert by rotation; energy differences determine relative populations (e.g., ethane rotation with staggered vs eclipsed forms;Fig. 1–21).
  • Pasteur’s optical activity and the concept of enantiomers (mirror images) and racemic mixtures; biological systems typically contain one enantiomer (e.g., L-amino acids in proteins; D-glucose).
• Box 1–1 Working in Biochemistry: Molecular mass, molecular weight, and units
  • Two equivalent ways to describe molecular mass: molecular weight (Mr), a dimensionless ratio; and molecular mass (m) in daltons (Da) or kilodaltons (kDa): 1 Da = 1/12 the mass of carbon-12; 1 kDa = 1000 Da; 1 u (atomic mass unit) = 1/12 the mass of C-12 ≈ 1.6606 × 10^{-24} g.
  • Distinctions between Mr and m; use of Da and u for single molecules; practical reasons for choosing units in biochemistry.
• Summary 1.2 (chemical foundations): carbon’s versatility; universal small-molecule metabolome; macromolecules as polymers; three-dimensional structure determined by configuration and conformation; stereospecific interactions underpin biology; experimental in vitro studies can miss vital cellular interactions.

1.3 Physical Foundations

• Living systems are dynamic steady states, not at equilibrium: open systems exchange matter and energy with surroundings; continuous synthesis and degradation of biomolecules occur to maintain steady state; energy investment is required to maintain order and function.
• Energy concepts and thermodynamics:
  • First Law (conservation of energy): energy cannot be created or destroyed, only transformed.
  • G = H − T S; free-energy change: ΔG = ΔH − T ΔS. A negative ΔG indicates a spontaneous (exergonic) process; positive ΔG indicates non-spontaneous (endergonic) processes.
  • For a reaction aA + bB ⇌ cC + dD, the reaction quotient Q = ([C]^c [D]^d)/([A]^a [B]^b); at constant temperature, ΔG = ΔG° + RT ln Q; when ΔG = 0, Q = Keq; and ΔG° = RT ln Keq.
  • When a reaction is at equilibrium (ΔG = 0), no net work can be done; ΔG° is a constant for the reaction that describes the position of equilibrium.
• Energy transduction in biology (Fig. 1–24 and 1–25, 1–28):
  • Photosynthesis captures light energy to drive electron flow from water to CO2, producing carbohydrates and releasing O2: 6 CO2 + 6 H2O → (light) C6H12O6 + 6 O2 (overall simplified representation).
  • Nonphotosynthetic organisms derive energy by oxidizing fuels; ATP is the primary energy currency, linking catabolic and anabolic processes.
  • ATP hydrolysis is highly exergonic: ATP → ADP + Pi; hydrolysis is a major energy source for endergonic cellular reactions. The hydrolysis of phosphoanhydride bonds releases free energy that is harnessed to drive unfavorable processes.
  • Coupling strategy: exergonic reactions can drive endergonic reactions by sharing intermediates (e.g., Pi), so that the sum ΔG3 = ΔG1 + ΔG2 is negative, enabling otherwise unfavorable syntheses (Fig. 1–26).
• Metabolic regulation and pathways:
  • Metabolism comprises many interconnected enzyme-catalyzed pathways; precursors and end products are balanced via regulation (e.g., feedback inhibition; isoleucine synthesis in E. coli).
  • Pathways are not isolated; they form a metabolic meshwork where changes in one metabolite ripple through others.
  • ATP-Acceptor coupling forms the metabolic backbone; ATP is central to both energy production and energy consumption in anabolic processes.
• Enzymes and catalysis:
  • Most biochemical reactions in cells require enzymes; enzymes accelerate rates by lowering activation energy (ΔG‡).
  • Enzymes stabilize the transition state; binding energy to the transition state lowers ΔG‡, increasing rate dramatically (often > 10^12-fold).
  • Enzyme activity is highly specific and regulated, enabling control over cellular metabolism.
• Summary 1.3 (physical foundations): organisms are open systems in a dynamic steady state; energy transduction from light or fuels powers cellular work; ΔG governs spontaneity and coupling; ATP is the central energy currency; metabolism is a regulated network of interdependent pathways.

1.4 Genetic Foundations

• The remarkable continuity of inheritance rests on DNA as the genetic material: DNA is a long polymer of nucleotides; sequence of nucleotides encodes information to build proteins and RNAs; DNA replication is semiconservative, producing two identical double helices, each serving as a template.
• DNA structure and replication (Fig. 1–30):
  • DNA is a double helix formed by two antiparallel strands; complementary base pairing: A with T, G with C; nucleotides linked by covalent bonds along each strand; hydrogen bonding between bases stabilizes the duplex.
  • When cells divide, strands separate; each strand serves as a template for synthesis of a new complementary strand; results in two identical double helices.
  • If one strand is damaged, the other strand provides a template for repair.
• DNA → RNA → Protein (Fig. 1–31): gene sequences in DNA are transcribed into RNA; RNA sequences are translated into proteins, which fold into functional three-dimensional structures; proteins may also form supramolecular complexes.
• RNA world and the origin of genetic material:
  • Early evolution may have featured RNA both as genome and catalyst; RNA could have catalyzed its own replication and the formation of peptides; later, DNA assumed the role of stable genetic repository and proteins emerged as major catalysts.
  • Ribosomes catalyze peptide bond formation using RNA as the catalytic core, consistent with an RNA-world scenario.
• Protein and nucleic acid self-assembly: macromolecules are highly organized; specific binding and noncovalent interactions drive formation of ribosomes, chromosomes, membranes, and other complexes.
• Box 1–2 Pasteur and optical activity: enantiomers rotate plane-polarized light in opposite directions; in biology, biomolecules are typically homochiral (proteins use L-amino acids; sugars are D-aldo-/keto-sugars).
• Box 1–3 Entropy and information: entropy measures randomness/disorder; information has a thermodynamic interpretation; living systems maintain low entropy (highly ordered) structures by exporting entropy to their surroundings via energy consumption; energy dissipation and information content are linked to molecular organization.
• Summary 1.4 (genetic foundations): DNA stores genetic information as a linear nucleotide sequence; replication is highly accurate; transcription and translation encode and implement genetic information; RNA may have preceded DNA in early life; macromolecules self-assemble into functional supramolecular complexes; Virchow’s dictum emphasizes cell lineage and reproduction.

1.5 Evolutionary Foundations

• Dobzhansky’s maxim: nothing in biology makes sense except in the light of evolution; metabolism, genetic code, and macromolecular structures reflect common ancestry and evolutionary conservation.
• Origin and early evolution:
  • Life arose >3.5 billion years ago; evidence of early life includes carbon isotope signatures from Greenland dating to ~3.85 billion years ago.
  • The earliest cells were likely chemoheterotrophs; energy initially obtained from environmental organic compounds.
  • Photosynthesis evolved, enabling CO2 reduction to organic matter; early electron donors included H2S, later water, producing O2 and shaping atmospheric oxygen levels.
  • Endosymbiosis: mitochondria originated from engulfed aerobic bacteria; plastids (chloroplasts) originated from engulfed cyanobacteria, enabling photosynthesis in plants/algae.
• Eukaryogenesis and diversification (Fig. 1–36):
  • Key changes in eukaryotes vs prokaryotes include: (i) more complex DNA packaging and chromosome segregation; (ii) development of intracellular membranes, separating transcription and translation; (iii) endosymbiotic events that introduced mitochondria and plastids.
• Linear vs. comprehensive evolution:
  • Cellular differentiation and multicellularity arose through specialization and cooperation among cells, leading to diverse tissues and organs.
• Molecular phylogeny:
  • Genome sequencing across organisms reveals deep evolutionary relationships; homologous genes share sequence similarity; orthologs have similar functions across species; paralogs arise from gene duplication within a species and may evolve new functions.
  • Phylogenetic trees derived from gene sequences complement and refine classical morphology-based trees (Fig. 1–4).
• Genomic scale and functional genomics:
  • Complete genomes exist for many organisms (Table 1–4); gene annotation reveals the proportion of the genome devoted to various cellular processes; many genes have unknown functions; transporters and protein synthesis components occupy significant fractions of genomes across species.
• Endpoints for medicine and biology:
  • Comparative genomics can identify genes underpinning major evolutionary innovations; differences among humans and primates inform disease susceptibility and developmental biology; genome sequencing informs diagnostics and therapy.
• Summary 1.5 (evolution): mutations and natural selection drive adaptation; life originated in a reducing, simple environment; RNA world possibly preceded DNA/protein world; endosymbiotic events gave rise to mitochondria and chloroplasts; molecular phylogeny and genomics reveal deep evolutionary relationships and medical insights; life is unified by shared molecular logic across domains.

BOXES AND FIGURES (selected highlights)

• Box 1–1 Working in Biochemistry: Molecular Weight and Units

  • Two equivalent ways to express molecular mass: Mr (molecular weight; dimensionless) and m (molar mass in Da); 1 Da = 1/12 the mass of C-12; 1 kDa = 1000 Da; 1 u ≈ 1.6606×10^{-24} g.
  • Distinguishing units helps relate measured masses to molecular counts and concentrations.

• Box 1–2 Louis Pasteur on Optical Activity

  • Pasteur separated enantiomeric crystals of tartaric acid; enantiomers rotate plane-polarized light in opposite directions; biomolecules in living systems are typically chiral and exist predominantly in a single enantiomer form (e.g., L-amino acids in proteins).

• Box 1–3 Entropy: A Conceptual Tour

  • Entropy increases with spreading of energy/matter; examples include heat transfer (teakettle to surroundings), oxidation of glucose producing CO2 and H2O, and information content (order vs disorder). Information can be viewed as negative entropy in biological contexts; living systems maintain low entropy by consuming free energy and exporting disorder to surroundings.

Key Equations (selected):

• Gibbs free energy for a process:
  $G = H - T S$
• Change in free energy for a process:
  $\Delta G = \Delta H - T \Delta S$
• Reaction quotient and free energy:
  $\Delta G = \Delta G^\circ + RT \ln Q,$ where
  $Q = \frac{[A]^a [C]^c}{[D]^d [B]^b}$ for aA + bB ⇌ cC + dD.
• Equilibrium and Keq:
  $\Delta G = 0 \;\Rightarrow\; Keq = Q<em>{eq}$ and $\Delta G^\circ = RT \ln K</em>{eq}$
• Activation energy and transition state:
  $\Delta G^\ddagger$ (activation energy barrier; lowered by enzymatic catalysis).
• ATP hydrolysis and energy coupling (schematic):
  $\text{ATP} \rightarrow \text{ADP} + \text{Pi}$
• Coupled reactions: if Reaction 1 is endergonic with (\Delta G1 > 0) and Reaction 2 is exergonic with (\Delta G2 < 0), the coupled reaction 3 has
  \Delta G3 = \Delta G1 + \Delta G_2 < 0.
• Central metabolic link:
  $\text{ATP} \rightarrow \text{ADP} + \text{Pi}$ acts as energy currency bridging catabolism and anabolism (Fig. 1–28).
• Cell as open system and metabolism as a network: open exchange of matter and energy; regulation maintains balance and economy (feedback inhibition; example with isoleucine synthesis in E. coli).
• DNA structure and base pairing (Fig. 1–30): A pairs with T, G pairs with C; two strands are complementary; semi-conservative replication yields two identical double helices.
• RNA to protein flow (Fig. 1–31): DNA → RNA → protein → folding and assembly into complexes.
• Endosymbiosis (Fig. 1–36): mitochondria and plastids originated from engulfed bacteria, later becoming integrated organelles within eukaryotic cells.

Summary across sections:

• 1.1 Cellular Foundations: cells share universal structures and processes; life is organized by a cytoskeleton and membrane systems; cellular organization is essential for metabolism and molecular interactions.
• 1.2 Chemical Foundations: carbon-based chemistry yields a universal metabolome; macromolecules (proteins, nucleic acids, polysaccharides, lipids) form intricate structures via noncovalent interactions; stereochemistry and functional groups define biomolecular behavior.
• 1.3 Physical Foundations: energy flow and thermodynamics govern all cellular processes; enzymes lower activation energy; metabolism integrates catabolic energy production with anabolic biosynthesis; ATP is central to energy coupling.
• 1.4 Genetic Foundations: DNA stores information; replication is highly accurate; transcription/translation produce proteins; RNA may have preceded DNA in early life; self-assembly of macromolecular complexes underlies cellular architecture.
• 1.5 Evolutionary Foundations: life stems from evolution via mutations and selection; endosymbiotic events shaped eukaryotes; comparative genomics reveals evolutionary relationships; the unity of biochemistry across life is reflected in conserved pathways and shared molecular machinery.

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