Chapter 2 Notes: Cell Chemistry and Bioenergetics
Chapter 2 Notes: Cell Chemistry and Bioenergetics
Focus: Chemical components of cells, noncovalent interactions, macromolecule structure, and how cells obtain and use energy (glycolysis, citric acid cycle, fermentation, and activated carriers).
Emphasis on how thermodynamics governs which reactions occur, how enzymes catalyze, and how energy is stored and transferred in the cell.
Equations are provided in LaTeX format where relevant.
The Chemical Components of a Cell
Water and its properties
Water is held together by hydrogen bonds between H and O; hydrogen bonds are relatively weak (~1/20 the strength of a covalent bond).
Hydrogen bonds are strongest when the donor, hydrogen, and acceptor atoms are collinear.
Water structure: transient hydrogen-bonded lattice; at 37°C, ~15% of water molecules are in flickering four-way hydrogen-bonded clusters, contributing to water’s unusual properties (high surface tension, high specific heat, high heat of vaporization).
Water as solvent: polar water dissolves ionic and polar substances (hydration shells around ions/polar molecules).
Noncovalent attractions in cells
Four major types of noncovalent attractions:
Ionic (electrostatic) attractions between fully charged groups.
Hydrogen bonds between electronegative atoms (O/N) and hydrogen.
van der Waals attractions between close-fitting surfaces.
Hydrophobic interactions driven by water exclusion; contributes to protein folding and membrane formation.
Noncovalent bonds specify macromolecular shape and binding to other molecules; many are required in concert for tight binding and precise recognition.
Relative strengths (typical values; in water or vacuum vary):
Covalent bonds: length ~0.10 nm; strength ~377 kJ/mol in vacuum; ~90 kcal/mol; much stronger than noncovalent bonds.
Ionic bonds: length ~0.25 nm; ~335 kJ/mol in vacuum; ~12.6 kcal/mol in water.
Hydrogen bonds: length ~0.17 nm; ~16.7 kJ/mol in vacuum; ~4.2 kJ/mol in water.
van der Waals attractions: length ~0.35 nm; ~0.4 kJ/mol (per atom) in vacuum and similar in water (weak, but collectively important when many contacts occur).
Tabulated comparison (Table 2-1): covalent, ionic, hydrogen, van der Waals with their characteristic strengths and lengths.
Polar molecules and acids/bases in water
Acids donate H+ in water; for example, carboxyl groups (-COOH) dissociate to give H+ (weak acids).
Bases accept H+; ammonia (NH3) + H+ ↔ NH4+. Water itself participates in hydronium H3O+ and hydroxide OH− equilibrium.
pH is defined as pH = −log10[H+], with pure water at pH ~7 at room temperature; pH describes acidity/basicity of solutions.
Hydrogen ion exchange: H+ can shuttle between water molecules (H2O ⇌ H+ + OH−) forming hydronium and hydroxyl ions; the process is rapid and reversible.
Carbon skeletons and organic building blocks
Carbon forms stable covalent bonds with itself, enabling chains, branched trees, and rings (skeletons essential for biomolecules).
Four major families of small organic molecules make up cells: sugars, amino acids, fatty acids (lipids), and nucleotides.
Macromolecules (proteins, nucleic acids, polysaccharides, lipids) have remarkable properties; their functions depend on precise three-dimensional structures held by covalent and noncovalent interactions.
Noncovalent bonds help specify macromolecular shape and binding specificity.
Carbon, Covalent Bonding, and Molecular Shape
Covalent bonds
Form when atoms share outer-shell electrons; each atom has a fixed number of covalent bonds in a defined arrangement.
Single bonds: two electrons shared; Double bonds: four electrons shared.
Covalent bonds fix geometry; rotation about a covalent bond can be restricted when multiple bonds or rigid structures are present.
The spatial arrangement of covalent bonds determines the three-dimensional shape and chemistry of molecules.
C–H (hydrocarbon) chemistry
Hydrocarbons (H–C chains) are nonpolar, hydrophobic, and generally insoluble in water.
Examples: methane, methyl groups, hydrocarbon tails of fatty acids.
Alternating double bonds and resonance
Carbon chains with alternating double bonds exhibit resonance stabilization; in aromatic rings like benzene, resonance contributes to stability.
C–O, C–N, and related functional groups
Alcohols (C–OH), carbonyls (C=O in aldehydes/ketones), carboxyl groups (-COOH) which can lose H+ to form -COO− in water.
Esters form from acids and alcohols; high-energy bonds can be present in acyl phosphates and phosphoanhydride linkages.
Amines (–NH2) can accept H+ to form –NH3+. Amides (C=O–NH) are uncharged in water (peptide bonds in proteins).
Sulfhydryl groups (-C–SH) in cysteine can form disulfide bonds (-S–S-), contributing to cross-links in proteins.
Phosphates and high-energy bonds
Inorganic phosphate (P) forms phosphate esters with hydroxyls and can be attached to proteins.
Phosphoanhydride bonds (e.g., in ATP) store high energy; hydrolysis releases energy used to drive biosynthetic processes.
Adenosine triphosphate (ATP) is a central activated carrier; hydrolysis to ADP and Pi releases energy to power cellular work.
Nucleophilic and base–sugar chemistry (nucleotides)
Nucleotides consist of a nitrogenous base, a five-carbon sugar (ribose or deoxyribose), and one or more phosphate groups.
N-glycosidic bonds link bases to the sugar at C1′; 5′ to 3′ phosphodiester bonds join nucleotides in nucleic acids.
Nucleotides act as activated carriers (ATP, NADH/NADPH, FADH2, acetyl-CoA, CoA derivatives) and as building blocks for nucleic acids.
Sugar chemistry
Monosaccharides general formula: $(CH2O)n$, where n = 3–8.
Aldoses (aldehyde group) vs ketoses (keto group).
Ring formation via intramolecular reaction between aldehyde/ketone and a hydroxyl group; forms α or β anomers depending on the orientation of the anomeric hydroxyl group.
Isomerism among monosaccharides (glucose, galactose, mannose) leads to different biological interactions.
Sugar derivatives: sugar molecules can be modified (e.g., glucosamine, N-acetylglucosamine, uridine diphosphate glucose).
Disaccharides and polysaccharides
Disaccharides form from two monosaccharides via dehydration (condensation) reactions (e.g., maltose = glucose + glucose; lactose = galactose + glucose; sucrose = glucose + fructose).
Complex oligosaccharides and polysaccharides (e.g., glycogen, starch) arise from repeating sugar units; glycogen is highly branched and serves as an energy store.
Lipids and fatty acids
Fatty acids have a carboxyl group at one end and a long hydrocarbon tail; can be saturated (no double bonds) or unsaturated (one or more double bonds). The presence of a double bond introduces a kink and affects packing and fluidity.
Triacylglycerols (triglycerides) store energy by esterifying three fatty acids to glycerol.
Phospholipids: glycerol with two fatty acid tails and a phosphate-containing head group; the phosphate is negatively charged and linked to a small polar group (e.g., choline). Major component of membranes; form lipid bilayers.
Steroids (e.g., cholesterol, testosterone): multi-ring structures with diverse biological roles, including membrane fluidity and hormone signaling.
Glycolipids: lipids with carbohydrate groups; important in membranes and cell recognition.
Polyisoprenoids and dolichol phosphate participate in glycoprotein and polysaccharide synthesis.
Other lipids
Lipids defined by water-insolubility and solubility in organic solvents; steroids and polyisoprenoids are common types beyond phospholipids.
Nucleotides, Nucleic Acids, and Their Derivatives
Nucleotides structure and naming
Base + sugar + phosphate groups; nucleotide names reflect their base (e.g., ATP, GTP, CTP, UTP; also NADH, FADH2, etc.).
Nucleotide nucleosides: base + sugar (adenosine, guanosine, cytidine, thymidine, uridine).
Abbreviations: single-letter bases A, G, C, T, U; nucleosides (adenosine, guanosine, cytidine, thymidine, uridine); nucleotides (AMP, ADP, ATP, etc.).
Phosphodiester backbone in nucleic acids
Nucleotides connect via phosphodiester bonds between 5′ and 3′ carbons of adjacent sugars.
The chain has a direction: 5′ end and 3′ end.
The phosphate group imparts negative charge to nucleic acids.
Nucleotide function and derivatives
Activated carriers store and transfer energy (ATP; NADH/NADPH; FADH2; acetyl CoA; SAM; UDP-glucose).
Coenzymes and signaling molecules (e.g., cyclic AMP, CAMP) participate in intracellular signaling and metabolism.
Monomer derivatives (e.g., GDP/GTP) participate in energy transfer and protein synthesis signaling networks.
Sugars in nucleotides
RNA uses ribose; DNA uses 2′-deoxyribose; numbered carbons are often marked with primes (5′, 3′).
Macromolecules and Their Assembly
Subunits and macromolecules
Subunits include sugars, amino acids, nucleotides, fatty acids; macromolecules are formed by linking these subunits covalently.
Condensation (dehydration) reactions form covalent bonds and water is released; hydrolysis breaks bonds and consumes water.
Noncovalent bonds in macromolecules
Noncovalent interactions influence folding and specificity; disruption of these bonds can unfold or misfold macromolecules.
Macromolecular assemblies (e.g., ribosome) rely on multiple noncovalent contacts for proper assembly.
The chemical landscape of the cell
The cell is dominated by macromolecules with remarkable properties; water, ions, small molecules, and inorganic components make up a minority fraction but are essential for function.
Energy, Thermodynamics, and Free Energy in Cells
Thermodynamics basics
First law: energy is conserved; energy can be transferred as heat or work.
Enthalpy: H = E + PV; heat transfer at constant pressure relates to change in enthalpy: AH is heat exchanged; exothermic if AH < 0, endothermic if AH > 0.
Entropy: S measures disorder; the second law states that systems spontaneously move toward states of higher probability (higher entropy) overall.
The Gibbs free energy: G = H − T S. ΔG predicts spontaneity at constant T and P. For a reaction in a closed system, ΔG < 0 favors spontaneity.
The universe’s entropy and free energy
The change in universal entropy for a reaction equals ΔSuniverse = ΔSsystem + ΔS_surroundings.
In cells, reactions are often driven by coupling an unfavorable reaction to a favorable one so that ΔG_total < 0.
Standard free-energy change and equilibrium
The standard free-energy change ΔG° relates to the equilibrium constant K: ΔG° = −RT ln K.
The actual free energy change under cellular conditions is ΔG = ΔG° + RT ln([products]/[reactants]).
At equilibrium, ΔG = 0 and K = [X]/[Y] when X and Y are interconvertible.
A table (Table 2-2) shows the relationship between ΔG° and K across several ranges of [X]/[Y] (e.g., K = 10^5 to 10^−5) to illustrate how large or small K values reflect very large or very small driving forces.
Coupled reactions and additive free energy
The free-energy changes of coupled reactions are additive: ΔGtotal = Σ ΔGi.
Activated carrier molecules are essential for biosynthesis because they provide the energy or reactive groups needed to push unfavorable reactions forward.
ATP and activated carriers
ATP is the most widely used activated carrier; hydrolysis of ATP (to ADP + Pi) provides energy to drive work and to form high-energy bonds in biosynthesis.
NADH and NADPH transfer electrons and hydrogens; FADH2 also serves as an electron carrier.
Other activated carriers include acetyl-CoA (acetyl group), carboxylated biotin (carboxylation), S-adenosylmethionine (methyl transfer), and UDP-glucose (glucose activation).
Enzymes and activation energy
Enzymes lower activation-energy barriers that block chemical reactions, enabling biological rates compatible with life.
Enzymes can steer substrates along specific reaction pathways and can be highly specific for substrates.
The enormous rapidity of molecular motions helps enzymes locate substrates efficiently.
How Cells Obtain Energy from Food
Glycolysis: central ATP-producing pathway
Overview: Converts one molecule of glucose into two molecules of pyruvate with energy capture in the form of ATP and NADH.
Phases: energy-investment phase (consumes ATP) followed by energy-generation phase (produces ATP and NADH).
Net yield per glucose: 2 ATP (substrate-level phosphorylation) and 2 NADH; 2 pyruvate produced.
Key steps and regulation:
Step 1: Glucose → glucose-6-phosphate (G6P) by hexokinase; trapped inside the cell by phosphorylation.
Step 2: G6P ⇌ fructose-6-phosphate (F6P) by phosphoglucose isomerase (isomerization).
Step 3: F6P → fructose-1,6-bisphosphate by phosphofructokinase (regulated; rate-limiting).
Step 4: Cleavage of fructose-1,6-bisphosphate into two triose phosphates (glyceraldehyde-3-phosphate, DHAP).
Step 5: DHAP isomerized to another glyceraldehyde-3-phosphate.
Step 6: Glyceraldehyde-3-phosphate is oxidized; NAD+ is reduced to NADH; a high-energy phosphate is formed (1,3-bisphosphoglycerate) – substrate-level phosphorylation forms ATP later.
Step 7: 1,3-bisphosphoglycerate transfers a phosphate to ADP to form ATP; enzyme: phosphoglycerate kinase.
Step 8: 3-phosphoglycerate is rearranged to 2-phosphoglycerate.
Step 9: Dehydration to phosphoenolpyruvate (high-energy phosphate bond).
Step 10: Phosphoenolpyruvate donates a phosphate to ADP to form ATP (pyruvate kinase).
Net energy, per glucose: 2 ATP (net) + 2 NADH + 2 pyruvate.
Regulation and energetics: glycolysis couples oxidation of glucose to production of ATP and NADH; Step 3 (phosphofructokinase) is highly regulated.
Fermentations in absence of oxygen
When oxygen is limited, cells regenerate NAD+ by reducing pyruvate to lactate (lactate fermentation) or by converting pyruvate to ethanol and CO2 (ethanol fermentation, e.g., in yeast).
Purpose: regenerate NAD+ to sustain glycolysis and ATP production under anaerobic conditions.
Energy stores and reservoirs
Organisms store energy as glycogen (polysaccharide) in animals and as starch (plants).
Fat storage occurs as triacylglycerols in adipocytes; fatty acids are released by hydrolysis and re-esterified.
Fatty acid catabolism and acetyl-CoA production
Sugars and fats are degraded to acetyl-CoA in mitochondria.
Fatty acids undergo beta-oxidation to yield acetyl-CoA, NADH, and FADH2 per cycle; the cycle shortens the fatty acyl chain by two carbons each turn.
The Citric Acid Cycle (TCA, Krebs cycle)
Oxidizes acetyl groups to CO2 and generates energy-rich carriers: NADH, FADH2, and GTP (or ATP).
Per turn: 3 NADH, 1 FADH2, 1 GTP (which can be converted to ATP), and 2 CO2 are released.
Key steps (with simplified terminology):
Step 1: Acetyl-CoA condenses with oxaloacetate to form citrate; citrate synthase catalyzes the reaction.
Step 2: Citrate is isomerized to isocitrate via aconitase.
Step 3: Isocitrate is oxidized and decarboxylated to α-ketoglutarate by isocitrate dehydrogenase, producing NADH and CO2.
Step 4: α-Ketoglutarate is oxidized and decarboxylated to succinyl-CoA by α-ketoglutarate dehydrogenase, producing NADH and CO2.
Step 5: Succinyl-CoA is converted to succinate with the formation of GTP (or ATP) via succinyl-CoA synthetase; CoA is released.
Step 6: Succinate is oxidized to fumarate by succinate dehydrogenase; FADH2 is generated.
Step 7: Fumarate is hydrated to malate by fumarase.
Step 8: Malate is oxidized to oxaloacetate by malate dehydrogenase, producing NADH.
Link to energy production: NADH and FADH2 feed into the electron transport chain to generate the majority of cellular ATP.
Electron transport and oxidative phosphorylation
The bulk of cellular ATP is produced by electron transport driving ATP synthase, powered by the proton-motive force generated across the mitochondrial membrane.
NADH and FADH2 donate electrons; the electron transport chain creates a proton gradient used to synthesize ATP from ADP and Pi.
Activated carriers beyond ATP
NADH and NADPH: Electron carriers used in catabolic (NADH) and anabolic (NADPH) pathways.
FADH2: Another electron carrier from the TCA and other dehydrogenases.
Acetyl-CoA: Donates an acetyl group in biosynthetic reactions and is a key entry point to the TCA cycle.
S-adenosylmethionine (SAM): Methyl group donor in many methylation reactions.
UDP-glucose: Activated sugar donor for polysaccharide and glycoprotein biosynthesis.
Coenzyme A (CoA) and CoA derivatives: Central in acyl-transfer reactions; acyl-CoA participates in beta-oxidation and lipid metabolism.
Energetics of polymer synthesis
Synthesis of biological polymers (proteins, nucleic acids, polysaccharides) is driven by ATP hydrolysis and energy-coupled reactions.
The overall process relies on the energy contained in activated carriers to form covalent bonds in polymers.
Connections to Foundational Principles and Real-World Relevance
Thermodynamics in biology
Cells cannot perform reactions that are thermodynamically unfavorable unless coupled to favorable reactions; Gibbs free energy (ΔG) governs spontaneity.
The standard free-energy change ΔG° and the equilibrium constant K provide a way to compare different reactions and predict direction under standard conditions; in cells, actual ΔG depends on metabolite concentrations.
Structure–function relationships
The precise shape of macromolecules, governed by covalent bonds and noncovalent interactions, determines function, substrate recognition, and regulation.
Energy flow in metabolism
Energy captured in activated carriers (ATP, NADH/NADPH, FADH2, acetyl-CoA, etc.) powers biosynthesis and mechanical work (e.g., muscle contraction).
Glycolysis, the TCA cycle, and oxidative phosphorylation form a coordinated network that extracts energy from nutrients and distributes it to drive cellular processes.
Biological significance of noncovalent interactions
Noncovalent bonds enable reversible interactions, protein folding, enzyme–substrate binding, DNA base pairing, and membrane assembly; disruptions can alter function or cause disease.
Practical implications
Understanding energy coupling explains why starving cells slow down biosynthesis and rely on stored fats; metabolic regulation ensures resources are allocated efficiently.
Knowledge of activated carriers informs drug design (e.g., targeting glycolytic flux in cancer cells) and metabolic engineering strategies.
Key Formulas and Concepts (LaTeX)
Covalent vs noncovalent bonds (conceptual strength):
Covalent bond strength: typically large (e.g., ~377 kJ/mol in vacuum for a typical C–C/C–N/C–O single bond).
Noncovalent bonds: substantially weaker; individual bonds can be weak, but many together provide tight binding.
Water and hydrogen bonding
Hydrogen bond length: ~0.17 nm; covalent O–H length ~0.096 nm.
Polarity and pH
pH = −
10[H^+]
Gibbs free energy and equilibrium
G = H − T S
ΔG = ΔH − T ΔS (constant T and P)
ΔG° = −R T
Relationship between standard free energy and equilibrium constant
ΔG° = −RT \, ln K
K = [X]/[Y] at equilibrium for the reaction Y → X
Free energy change under cellular conditions
ΔG = ΔG° + RT \, ln([products]/[reactants])
Coupled reactions and universe entropy (conceptual)
ΔGuniverse = ΔSuniverse × T = ΔSbox × T + ΔSsea × T; in panel terms, a reaction proceeds if ΔG_universe < 0 (equivalently, ΔG < 0 under appropriate accounting).
Net energy yield from glycolysis (per glucose)
Net: 2 ATP (substrate-level phosphorylation) and 2 NADH; 2 pyruvate produced.
Citric acid cycle output per turn
3 NADH + 1 FADH2 + 1 GTP (or ATP) + 2 CO2
General scheme for glycolysis steps (overview)
Glucose → G6P (hexokinase); isomerization to F6P; phosphorylation to fructose-1,6-bisphosphate; cleavage to two triose phosphates; oxidation and substrate-level phosphorylation yielding ATP and NADH; net yield as above.
Quick Glossary (for rapid recall)
Hydroxyl group: –OH
Carboxyl group: –COOH (pKa ~ around physiological range; becomes –COO− in water)
Phosphate group: –PO3^2− (often forms high-energy bonds in phosphate esters and phosphoanhydrides)
Activated carrier: a molecule like ATP, NADH, or acetyl-CoA that stores and transfers energy or reactive groups
Anomer: α or β form of cyclic sugar (depends on the orientation of the ring-forming hydroxyl group)
Glycosidic bond: linkage between sugar units in carbohydrates
Fatty acid saturation: saturated (no double bonds) vs unsaturated (has one or more double bonds, causing kinks)
Ketone vs aldehyde: carbonyl group position defines the sugar class (ketose vs aldose)
Anaplerotic reactions: metabolic reactions that replenish TCA cycle intermediates (not explicitly named here, but related to cycle flux)
If you’d like, I can convert this into a printable PDF-style outline or extract specific sections (e.g., a detailed step-by-step glycolysis chart, or a labeled diagram guide) to match your study plan. Also, tell me which sections you want emphasized for the exam (thermodynamics, glycolysis specifics, or energy carriers) and I’ll tailor the notes accordingly.