Week 4

Microbial Metabolism

10 sub-topics · Pages 169–209

📄 Lecture Slides – Microbial Metabolism Page of ⬇ Download
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1. Introduction

📖 Lecturer's Note

Metabolism is the sum of all chemical reactions in a living cell. The first law of thermodynamics governs energy conservation; the second sets limits on efficiency. Catabolic reactions break down organic molecules, releasing energy stored as ATP and reducing equivalents (NADH, FADH₂). Anabolic reactions consume this energy to build biomolecules. The coupling of catabolism to anabolism is mediated by ATP — the universal cellular energy currency.

✏️ Fill in the Blank

1. The change in free energy of a reaction at standard biological conditions (pH 7, 25°C) is represented by the symbol _______.

Show Answer ΔG°'

🔘 Multiple Choice

1. Which of the following best describes a coenzyme?

  • A) A protein component of an enzyme that provides structural support
  • B) A small, non-protein organic molecule that carries chemical groups or electrons between enzymes
  • C) An inorganic metal ion required for enzyme function
  • D) A molecule that permanently binds to the enzyme active site
Show Answer Correct: B) A small, non-protein organic molecule that carries chemical groups or electrons between enzymes

2. Which metabolic pathway do many bacteria use instead of glycolysis to produce pentose sugars for nucleotide synthesis?

  • A) Krebs cycle
  • B) Entner-Doudoroff pathway
  • C) Pentose phosphate pathway
  • D) Glyoxylate cycle
Show Answer Correct: C) Pentose phosphate pathway

💬 Open-Ended Questions

1. What is the proton motive force (PMF) and how is it generated in bacteria? Explain its role beyond ATP synthesis.

Hint / Guidance PMF = electrochemical gradient across plasma membrane consisting of a chemical gradient (ΔpH) and an electrical gradient (Δψ). Generated by: electron transport chain pumping protons (H⁺) from cytoplasm to periplasm; also by bacteriorhodopsin (light-driven proton pump in halophilic Archaea). Beyond ATP synthesis: (1) Active transport: secondary transporters use PMF to drive nutrient uptake (symporters, antiporters) — e.g., lactose permease; (2) Flagellar rotation: MotA/B stator uses proton flow to rotate flagellum; (3) Reverse electron transport: PMF drives electrons to NAD⁺ in chemolithotrophs with low-potential electron donors.

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📖 Lecturer's Note

Endergonic reactions (ΔG > 0) consume energy and cannot proceed spontaneously. In cells, they are driven by coupling to exergonic reactions (ΔG < 0) such as ATP hydrolysis (ΔG = −30.5 kJ/mol) or pyrophosphate hydrolysis. This thermodynamic coupling principle underlies all biosynthesis — from peptide bond formation to DNA replication to active transport against concentration gradients.

✏️ Fill in the Blank

1. Metabolic reactions that release free energy (negative ΔG) and can proceed spontaneously are called _______ reactions.

Show Answer Exergonic

🔘 Multiple Choice

1. A reaction has ΔG°' = −45 kJ/mol. Which statement is correct?

  • A) The reaction is endergonic and requires energy input
  • B) The reaction is exergonic and proceeds spontaneously under standard conditions
  • C) The reaction produces no net change in free energy
  • D) The reaction can only occur if coupled to ATP hydrolysis
Show Answer Correct: B) The reaction is exergonic and proceeds spontaneously under standard conditions

2. The enzyme that catalyses the fixation of CO₂ in the Calvin cycle is:

  • A) Hexokinase
  • B) Pyruvate carboxylase
  • C) RuBisCO
  • D) Isocitrate lyase
Show Answer Correct: C) RuBisCO

💬 Open-Ended Questions

1. A researcher adds a proton ionophore (e.g., CCCP) to a bacterial culture. This molecule collapses the proton gradient across the membrane. Predict the metabolic consequences for aerobic and fermentative bacteria separately.

Hint / Guidance Aerobic bacteria: ETC continues to pump protons but gradient is immediately dissipated — ATP synthase cannot generate ATP; all energy from electron transport is lost as heat; only substrate-level phosphorylation (glycolysis) remains; growth halts; cell depletes ATP reserves; eventually dies. Fermentative bacteria: less affected initially — do not rely on PMF for ATP synthesis (substrate-level only); however, active transport driven by PMF fails — nutrient uptake impaired; flagellar motility ceases; secondary metabolite secretion affected; long-term growth severely impaired.

3. Activation Energy and Catalysis

📖 Lecturer's Note

Enzymes are biological catalysts that accelerate reaction rates by lowering the activation energy barrier without being consumed in the reaction. They achieve this by binding substrates in a specific orientation, stabilising the transition state, and providing microenvironments that facilitate bond rearrangements. A single enzyme molecule can catalyse up to 10⁶ reactions per second — a rate enhancement of many orders of magnitude over the uncatalysed reaction.

✏️ Fill in the Blank

1. The energy required to initiate a chemical reaction, even if the overall reaction is exergonic, is called the _______ energy.

Show Answer Activation

🔘 Multiple Choice

1. Feedback inhibition in a biosynthetic pathway means that:

  • A) The first substrate activates the last enzyme in the pathway
  • B) The end-product of the pathway inhibits the first enzyme (committed step), preventing overproduction
  • C) All enzymes in the pathway are inhibited simultaneously by the substrate
  • D) The pathway is activated when the cell has excess energy
Show Answer Correct: B) The end-product of the pathway inhibits the first enzyme (committed step), preventing overproduction

2. Anabolism differs from catabolism in that anabolism:

  • A) Releases energy and breaks down molecules
  • B) Uses energy to synthesise complex molecules from simpler ones
  • C) Only occurs under aerobic conditions
  • D) Produces CO₂ and H₂O as end products
Show Answer Correct: B) Uses energy to synthesise complex molecules from simpler ones

💬 Open-Ended Questions

1. Explain how autotrophic microorganisms fix CO₂ using the Calvin-Benson-Bassham cycle. What is the role of RuBisCO, and what are the energy costs per molecule of CO₂ fixed?

Hint / Guidance CBB cycle: CO₂ + ribulose-1,5-bisphosphate (RuBP) → 2 molecules of 3-phosphoglycerate (3-PGA) — catalysed by RuBisCO (ribulose-1,5-bisphosphate carboxylase/oxygenase). 3-PGA reduced using ATP and NADPH → glyceraldehyde-3-phosphate (G3P) → regeneration of RuBP. Net: 3 CO₂ + 9 ATP + 6 NADPH → 1 G3P (can be used for biosynthesis). Energy cost: very high; 3 ATP and 2 NADPH per CO₂; explains why heterotrophy is more efficient. RuBisCO limitation: also catalyses wasteful oxygenase reaction (photorespiration) at high O₂.

4. Enzymes

📖 Lecturer's Note

Enzyme specificity arises from the precise complementarity between the enzyme's active site and its substrate — the 'lock-and-key' (Fischer) or 'induced fit' (Koshland) model. Enzyme activity is sensitive to temperature (optimum ~37°C for mesophiles, >80°C for hyperthermophile enzymes), pH (each enzyme has a characteristic pH optimum), substrate concentration, and the presence of inhibitors or activators.

✏️ Fill in the Blank

1. Biochemical reactions in which electrons are transferred from a donor (which is oxidised) to an acceptor (which is reduced) are called _______ reactions.

Show Answer Redox (oxidation-reduction)

🔘 Multiple Choice

1. Which type of phosphorylation generates ATP by directly transferring a phosphate group from a phosphorylated substrate to ADP, without requiring the electron transport chain?

  • A) Oxidative phosphorylation
  • B) Photophosphorylation
  • C) Substrate-level phosphorylation
  • D) Chemiosmotic phosphorylation
Show Answer Correct: C) Substrate-level phosphorylation

2. Which statement about the proton-motive force is correct?

  • A) It is created by the flow of electrons through the Calvin cycle
  • B) It consists of a chemical gradient (ΔpH) and an electrical gradient (Δψ) across the membrane
  • C) It drives substrate-level phosphorylation in glycolysis
  • D) It is only found in eukaryotic mitochondria
Show Answer Correct: B) It consists of a chemical gradient (ΔpH) and an electrical gradient (Δψ) across the membrane

💬 Open-Ended Questions

1. Describe how temperature affects enzyme-catalysed reaction rates in microorganisms. How do thermophilic bacteria maintain enzyme function at high temperatures?

Hint / Guidance At low T: reaction rate increases with T (Arrhenius — more molecules have sufficient activation energy); Q₁₀ ≈ 2 for biological reactions. Above optimum T: denaturation of enzyme outweighs rate increase; active site geometry disrupted; rapid loss of activity. Thermophilic adaptations: (1) More thermostable bonds: salt bridges, disulfide bonds, hydrophobic packing, proline substitutions reduce conformational flexibility; (2) Chaperone proteins re-fold denatured enzymes; (3) Membrane adapted with higher proportion of saturated lipids; (4) Thermostable DNA polymerases (e.g., Taq from Thermus aquaticus) maintain function at 95°C — exploited in PCR.

5. Michaelis-Menten Curve

📖 Lecturer's Note

The Michaelis-Menten curve — a hyperbolic plot of reaction velocity (v) against substrate concentration ([S]) — is the graphical signature of enzyme kinetics. At low [S], v increases nearly linearly (first order kinetics); at high [S], v plateaus at Vmax (zero order kinetics) as all active sites are saturated. The half-maximum velocity occurs at [S] = Km, the Michaelis constant.

✏️ Fill in the Blank

1. The overall set of all chemical reactions in a living cell — including both energy-releasing and energy-consuming reactions — is called _______.

Show Answer Metabolism

🔘 Multiple Choice

1. Enzyme activity is typically highest at the optimum temperature and pH for that organism. Above the optimum temperature, enzyme activity rapidly decreases because:

  • A) The substrate concentration becomes rate-limiting
  • B) Thermal energy disrupts non-covalent bonds maintaining the enzyme's three-dimensional shape, causing denaturation
  • C) ATP production increases and inhibits enzyme function
  • D) The cell membrane becomes impermeable to substrates
Show Answer Correct: B) Thermal energy disrupts non-covalent bonds maintaining the enzyme's three-dimensional shape, causing denaturation

💬 Open-Ended Questions

1. Two bacteria grow on the same carbon source but one uses aerobic respiration and the other uses fermentation. Compare their growth yields (biomass per gram of substrate) and explain the metabolic basis for the difference.

Hint / Guidance Aerobic respiration: ~30–32 ATP per glucose → high growth yield (~0.5 g cell dry weight per g glucose); complete oxidation of substrate to CO₂ and H₂O. Fermentation: only 2 ATP per glucose (substrate-level phosphorylation only) → low growth yield (~0.05–0.1 g per g glucose); substrate partially oxidised (ethanol, lactic acid as end-products — still contain energy). Metabolic basis: ETC in aerobic respiration harvests energy from NADH/FADH₂ via PMF; fermentation must re-oxidise NADH using organic electron acceptors (no additional ATP gained). Environmental implication: aerobic organisms grow faster and produce more biomass from same substrate.

2. A bacterium is growing anaerobically in a glucose medium and produces ethanol and CO₂. Identify the fermentation pathway and explain why NAD⁺ regeneration is essential.

Hint / Guidance Alcoholic fermentation (e.g., Zymomonas mobilis, yeasts): pyruvate → acetaldehyde (pyruvate decarboxylase) → ethanol (alcohol dehydrogenase). NAD⁺ regeneration: glycolysis reduces NAD⁺ to NADH; without an electron acceptor (O₂ absent) NADH accumulates and glycolysis stops. Fermentation oxidises NADH back to NAD⁺ using organic compounds (acetaldehyde), allowing glycolysis to continue. Only 2 ATP net per glucose via substrate-level phosphorylation.

6. Michaelis-MentenEquation

📖 Lecturer's Note

Km (the Michaelis constant) quantifies the affinity between enzyme and substrate: a low Km means the enzyme is half-saturated at very low [S] — high affinity. Vmax reflects the maximum catalytic capacity and depends on enzyme concentration and the catalytic rate constant (kcat). The ratio kcat/Km ('catalytic efficiency') is the key measure of enzyme performance in the cell.

✏️ Fill in the Blank

1. The metabolic pathway that converts glucose to two pyruvate molecules, producing 2 ATP and 2 NADH, is called _______.

Show Answer Glycolysis (Embden-Meyerhof-Parnas pathway)

🔘 Multiple Choice

1. Enzymes accelerate metabolic reactions by:

  • A) Increasing the free energy of products
  • B) Shifting the equilibrium toward products
  • C) Lowering the activation energy without being consumed
  • D) Providing electrons for redox reactions
Show Answer Correct: C) Lowering the activation energy without being consumed

💬 Open-Ended Questions

1. Explain the role of ATP in microbial metabolism. How is it produced during catabolism and consumed during anabolism? Why is it described as the 'energy currency' of the cell?

Hint / Guidance ATP produced by: substrate-level phosphorylation (direct transfer from high-energy phosphorylated compound, e.g., PEP → pyruvate in glycolysis) and oxidative phosphorylation (chemiosmosis via ATP synthase). Consumed in: biosynthesis (peptide bond formation), active transport (ABC transporters), motility (flagellar rotation), signal transduction. 'Energy currency': ATP links exergonic (ΔG < 0) and endergonic (ΔG > 0) reactions — energy released by catabolism is conserved as ATP and spent in anabolism; like currency, can be produced and spent in different cellular locations.

2. Explain the concept of metabolic versatility in bacteria. Give two examples of bacteria that can switch between different energy sources depending on environmental conditions.

Hint / Guidance Metabolic versatility: ability to use multiple carbon/energy sources; regulated by catabolite repression and sensor-regulator two-component systems. Examples: (1) Paracoccus denitrificans — can respire aerobically on organic compounds, perform denitrification (NO₃⁻ → N₂) anaerobically, or grow lithoautotrophically on H₂; (2) Rhodobacter sphaeroides — photoheterotrophic (light + organic C), photoautotrophic (light + CO₂), or chemoorganoheterotrophic in dark depending on light and O₂ availability.

7. Lineweaver-Burk (double reciprocal plot)

📖 Lecturer's Note

The Lineweaver-Burk double reciprocal plot (1/v vs 1/[S]) linearises Michaelis-Menten kinetics, allowing graphical determination of Km (from x-intercept = −1/Km) and Vmax (from y-intercept = 1/Vmax). It also distinguishes inhibition types: competitive inhibition shifts the x-intercept; non-competitive shifts the y-intercept; uncompetitive inhibition shifts both intercepts equally (parallel lines).

✏️ Fill in the Blank

1. The final electron acceptor in aerobic respiration is _______.

Show Answer Oxygen (O₂)

🔘 Multiple Choice

1. Which statement correctly describes the relationship between catabolism and anabolism?

  • A) Both catabolism and anabolism release energy
  • B) Catabolism breaks down molecules releasing energy; anabolism builds molecules consuming energy
  • C) Anabolism occurs only in aerobic organisms
  • D) Catabolism requires ATP as a direct energy input
Show Answer Correct: B) Catabolism breaks down molecules releasing energy; anabolism builds molecules consuming energy

💬 Open-Ended Questions

1. A mutant bacterium produces a key glycolytic enzyme with 10× higher Km (lower substrate affinity) than wild type. Predict the metabolic consequences at low and high glucose concentrations. How might this affect the organism's survival in a competitive environment?

Hint / Guidance High Km = enzyme requires higher substrate concentration for half-maximal velocity. At low glucose: wild-type enzyme is nearly saturated (efficient); mutant enzyme is far below saturation — glycolytic flux severely reduced → less ATP → slower growth. At high glucose: mutant may approach normal rates if substrate concentration >> Km. Competitive disadvantage: in nutrient-limited environments (most natural environments), mutant cannot efficiently extract energy from scarce glucose; outcompeted by wild-type organisms with higher affinity enzymes.

2. Compare the ATP yields of aerobic respiration, anaerobic respiration (using nitrate), and lactic acid fermentation per mole of glucose, and explain the biochemical reasons for the differences.

Hint / Guidance Aerobic: ~30–32 ATP; full ETC with O₂ (high reduction potential +0.82V) maximises ΔG and H⁺ pumping; 10 NADH + 2 FADH₂ → ~26 ATP via oxidative phosphorylation + 4 ATP substrate-level. Anaerobic (NO₃⁻): ~19 ATP; nitrate reductase complex pumps fewer H⁺; lower reduction potential of NO₃⁻/N₂ (+0.74V) than O₂ gives less ΔG. Lactic acid fermentation: 2 ATP; no ETC; substrate-level only; all NADH oxidised by lactate dehydrogenase.

8. Competitive Inhibition

📖 Lecturer's Note

Competitive inhibitors are molecules that structurally resemble the substrate and compete for the same active site. They increase the apparent Km (the enzyme appears to have lower affinity) but do not change Vmax — because sufficient substrate can outcompete the inhibitor. This is clinically exploited: methotrexate competitively inhibits dihydrofolate reductase; sulphonamides competitively inhibit bacterial dihydropteroate synthase.

✏️ Fill in the Blank

1. The cyclic metabolic pathway in which acetyl-CoA is oxidised to CO₂ and high-energy electron carriers are produced is the _______.

Show Answer Krebs cycle (TCA cycle / citric acid cycle)

🔘 Multiple Choice

1. An enzyme's active site is blocked by a molecule structurally similar to the substrate. This is an example of:

  • A) Allosteric inhibition
  • B) Competitive inhibition
  • C) Non-competitive inhibition
  • D) Feedback activation
Show Answer Correct: B) Competitive inhibition

💬 Open-Ended Questions

1. Describe the concept of metabolic regulation through feedback inhibition using isoleucine biosynthesis as a specific example. Why is this important for microbial economy?

Hint / Guidance Isoleucine pathway: threonine → α-ketobutyrate → ... → isoleucine (5 steps). End-product isoleucine inhibits threonine deaminase (first committed step) allosterically — isoleucine binds regulatory site, changes conformation, reduces activity. When isoleucine is abundant: pathway shuts down (saves carbon/energy); when depleted: inhibition released, pathway active. Economy: prevents overaccumulation of amino acids (osmotic stress); conserves precursor carbon skeletons for other uses; allows rapid response to changing nutrient availability without gene regulation delay.

2. What is the glyoxylate cycle and in which organisms/conditions is it found? Why can it not operate in humans?

Hint / Guidance Glyoxylate cycle: modified TCA cycle using isocitrate lyase and malate synthase to bypass CO₂-releasing steps; converts 2 acetyl-CoA → succinate (net); allows growth on C2 compounds (acetate, fatty acids) as sole carbon source. Found in: bacteria, fungi, plants, nematodes. Absent in vertebrates — no isocitrate lyase gene; therefore mammals cannot synthesise glucose from fat (net), explaining why fatty acids cannot replenish oxaloacetate for gluconeogenesis beyond negligible amounts.

9. No substrate inhibitionSubstrateinhibitionSv

📖 Lecturer's Note

At supraoptimal substrate concentrations, some enzymes show substrate inhibition — a second substrate molecule binds to a non-productive site, reducing activity. This is seen in ammonia monooxygenase (nitrifying bacteria) at high ammonia concentrations and has practical implications for bioreactor design in wastewater nitrification, where ammonia loading must be carefully controlled.

🔘 Multiple Choice

1. In allosteric regulation, an enzyme's activity is modulated by a molecule that binds at:

  • A) The active site, directly competing with the substrate
  • B) A site other than the active site, causing a conformational change
  • C) The substrate, preventing it from entering the active site
  • D) The cofactor binding region only
Show Answer Correct: B) A site other than the active site, causing a conformational change

2. In oxidative phosphorylation, ATP is synthesised by:

  • A) Substrate-level phosphorylation in glycolysis
  • B) ATP synthase driven by the proton-motive force
  • C) Direct reduction of NAD⁺
  • D) The phosphoketolase pathway
Show Answer Correct: B) ATP synthase driven by the proton-motive force

💬 Open-Ended Questions

1. Compare oxidative and substrate-level phosphorylation. Under what circumstances would a bacterium rely exclusively on substrate-level phosphorylation, and what are the implications for energy yield?

Hint / Guidance Substrate-level phosphorylation: direct transfer of phosphoryl group from metabolic intermediate to ADP (e.g., pyruvate kinase in glycolysis, succinyl-CoA synthetase in TCA); no membrane required; occurs during glycolysis and TCA. Oxidative phosphorylation: requires electron transport chain + ATP synthase + membrane; uses proton motive force (PMF). Relies exclusively on substrate-level phosphorylation when: no functional ETC, oxygen and alternative electron acceptors absent (strict fermentation). Energy yield: 2 ATP per glucose (fermentation) vs. 30–32 ATP (aerobic respiration) — severe limitation for growth rate and biomass yield.

2. Describe how bacteria regulate metabolic pathways to avoid wasting energy on synthesis of already-abundant metabolites. Use feedback inhibition and operon repression as examples.

Hint / Guidance Feedback inhibition: end product of pathway allosterically inhibits first enzyme (e.g., isoleucine inhibits threonine deaminase in Ile biosynthesis); fast, reversible, acts at protein level. Operon repression: repressor protein (aporepressor) binds corepressor (end product) → active repressor binds operator → blocks transcription of biosynthetic genes; e.g., trp operon repressed when tryptophan is abundant. Together: immediate (enzymatic) and long-term (transcriptional) control prevents overproduction.

10. GLIIXVLEOH

📖 Lecturer's Note

Membrane transport mechanisms determine which substrates enter the cell and how efficiently they are acquired. Simple diffusion is limited to small, lipid-soluble molecules. Facilitated diffusion (porins, permeases) speeds up hydrophilic solute entry down concentration gradients. Active transport (ABC transporters, proton symporters) moves solutes against gradients at the cost of ATP or PMF, enabling cells to concentrate nutrients from dilute environments.

🔘 Multiple Choice

1. Which of the following statements about NAD⁺ is correct?

  • A) NAD⁺ is the oxidised form and acts as an electron donor in catabolic reactions
  • B) NAD⁺ is the oxidised form; it accepts electrons from substrates during catabolism, becoming NADH
  • C) NADH is the oxidised form and donates protons to the electron transport chain
  • D) NAD⁺ is produced by the electron transport chain as an end-product
Show Answer Correct: B) NAD⁺ is the oxidised form; it accepts electrons from substrates during catabolism, becoming NADH

2. Fermentation differs from respiration in that fermentation:

  • A) Produces more ATP per glucose molecule
  • B) Requires oxygen as the final electron acceptor
  • C) Uses organic molecules as the final electron acceptor and regenerates NAD⁺
  • D) Always occurs in the mitochondria
Show Answer Correct: C) Uses organic molecules as the final electron acceptor and regenerates NAD⁺

💬 Open-Ended Questions

1. Explain the difference between a constitutive enzyme and an inducible enzyme in bacteria. Give an example of each and explain the advantage of having inducible enzymes from an energy conservation standpoint.

Hint / Guidance Constitutive enzyme: always expressed regardless of substrate presence (e.g., glycolytic enzymes — glucose metabolism always needed). Inducible enzyme: expressed only when its substrate (inducer) is present (e.g., β-galactosidase induced by lactose in E. coli; lac operon). Energy conservation: synthesising proteins is energetically expensive (ATP + GTP for translation); if substrate is absent, producing enzyme wasteful. Induction ensures enzyme is made only when needed — saves resources, allows rapid adaptation to new substrates, prevents diversion of precursors.
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