🎯Diagnostic: Test Your Starting Level18 questions (2 per section). No prior reading required - see what you already know.
Aim to answer every question before checking. Missed questions point you to the sections you need most.
1. (10.1) The pyruvate dehydrogenase (PDH) complex converts:
C. PDH bridges glycolysis (cytoplasm) to the TCA cycle (mitochondrial matrix). Irreversible and tightly regulated. Uses 5 cofactors: TPP (B1), lipoamide, CoA (B5), FAD (B2), NAD+ (B3). Thiamine deficiency (beriberi) impairs PDH.
2. (10.1) PDH is allosterically inhibited by:
A. Product inhibition: when acetyl-CoA and NADH pile up (or energy is abundant = high ATP), PDH slows. PDH kinase (which phosphorylates and inactivates PDH) is stimulated by these same signals. PDH phosphatase reverses it when calcium/insulin demand more fuel.
3. (10.2) Per acetyl-CoA, one turn of the TCA cycle produces:
B. Per acetyl-CoA: 3 NADH (at isocitrate DH, α-KG DH, malate DH), 1 FADH2 (at succinate DH), 1 GTP (at succinyl-CoA synthetase), 2 CO2 released (at isocitrate DH and α-KG DH). The 2 carbons of acetyl-CoA are fully oxidized.
4. (10.2) Which TCA cycle enzyme is also part of the electron transport chain (Complex II)?
D. Succinate DH is embedded in the inner mitochondrial membrane. It oxidizes succinate to fumarate (TCA step) while reducing FAD to FADH2, then directly passes electrons to ubiquinone (Q). The only TCA enzyme not in the matrix.
5. (10.3) The TCA cycle's major control point is:
A. Isocitrate DH is the rate-limiting TCA enzyme. Three major regulators: Ca2+ (exercising muscle) activates; ADP activates; ATP/NADH inhibit. α-KG DH and citrate synthase also respond to energy charge but to a lesser degree.
6. (10.3) Why does the TCA cycle accelerate during exercise?
C. Muscle contraction releases Ca2+ from sarcoplasmic reticulum; some leaks into mitochondria where it activates three key dehydrogenases. Combined with high ADP (signal of ATP consumption), this ramps up the cycle to meet demand.
7. (10.4) Which ETC complex transfers electrons from FADH2 (not NADH) to ubiquinone?
B. Complex I takes electrons from NADH. Complex II takes them from FADH2 (via succinate DH). Because Complex II does not pump protons, FADH2 yields less ATP than NADH (~1.5 vs. 2.5 ATP per electron pair in modern estimates).
8. (10.4) The final electron acceptor of the ETC is:
D. Complex IV (cytochrome c oxidase) transfers 4 electrons to O2, making 2 H2O. This is why we breathe oxygen - it pulls electrons through the whole chain. Without O2, the ETC backs up and ATP production crashes.
9. (10.5) ATP synthase is powered by:
A. The proton gradient built by Complexes I/III/IV is tapped by ATP synthase. Protons flow through the rotor, causing rotation that mechanically activates the F1 catalytic sites (binding-change mechanism). ~3-4 H+ per ATP synthesized.
10. (10.5) The chemiosmotic theory (Peter Mitchell) states that:
C. Mitchell's 1961 hypothesis - electron-transport energy is converted to a proton-motive force (pH gradient + membrane potential), not a direct chemical intermediate. He won the 1978 Nobel Prize for this counterintuitive but correct idea.
11. (10.6) Cyanide is lethal because it:
B. With Complex IV blocked, electrons back up through the chain, NADH/FADH2 accumulate, and ATP production crashes. Cells starve even though O2 is plentiful (cells can't use it). Tissues with highest ATP demand (brain, heart) die first.
12. (10.6) Rotenone inhibits:
D. Used as a fish poison and pesticide. Blocks Complex I, preventing NADH from feeding into the chain (but FADH2 can still enter at Complex II). Linked to Parkinson's in chronic exposure studies.
13. (10.7) An "uncoupler" like 2,4-dinitrophenol (DNP) or thermogenin (UCP1):
A. Uncouplers allow H+ to bypass ATP synthase. Electron transport revs up (no back-pressure from the gradient) but ATP production crashes. Energy dissipates as heat - the physiological role of UCP1 in brown fat (nonshivering thermogenesis in newborns and hibernators).
14. (10.7) DNP was briefly marketed as a weight-loss drug because it:
C. DNP massively raises metabolic rate by dissipating the proton gradient. Use causes lethal hyperthermia - body temp rises uncontrollably. Banned, but sometimes abused illicitly with fatal results.
15. (10.8) Total aerobic ATP yield per glucose is approximately:
B. Older textbooks say "38 ATP"; modern stoichiometry (NADH → ~2.5 ATP; FADH2 → ~1.5 ATP; shuttle costs in neurons/muscle) gives 30-32. You may see either - the MCAT accepts both ranges.
16. (10.8) Of the total ATP yield from glucose, glycolysis contributes:
D. Glycolysis: net 2 ATP + 2 NADH. In glycerol-3-phosphate shuttle tissues (muscle/brain), the 2 cytoplasmic NADH effectively enter as FADH2 (1.5 each ≈ 3), so glycolysis ≈ 5 ATP total. In heart/liver (malate-aspartate shuttle) they enter as NADH (2.5 each ≈ 5), so glycolysis ≈ 7 ATP.
17. (10.9) During the fed state, which pathways dominate?
C. Fed state = insulin high. Glucose is consumed (glycolysis), stored (glycogen), or converted to fat (fatty acid synthesis in liver). Catabolic pathways like β-oxidation, gluconeogenesis, and ketogenesis are suppressed.
18. (10.9) During prolonged fasting, which tissues can continue to use glucose?
A. RBCs have no mitochondria - glucose is their only fuel. Renal medulla is hypoxic. Brain needs ~120 g glucose/day initially but adapts to use ketone bodies, reducing glucose demand to ~40 g/day. Liver runs gluconeogenesis to supply glucose.
Previous Attempts
Aerobic respiration is what happens to pyruvate when oxygen is available. Pyruvate is fully oxidized to CO2 through the TCA cycle, and the electrons harvested there (as NADH and FADH2) are passed to the electron transport chain, which pumps protons to build a gradient that ATP synthase uses to make ATP. The net result: ~30-32 ATP per glucose, vastly more than glycolysis alone produces.
This Chapter Continues Where Chapter 9 Left Off
Chapter 9 ended at pyruvate. This chapter picks up there. The flow you should keep in your head:
Pyruvate → PDH → Acetyl-CoA → TCA cycle (a.k.a. citric acid cycle, Krebs cycle) → NADH and FADH2 → electron transport chain → proton gradient → ATP synthase → ATP.
Each step hands off a product that is the next step’s substrate. The main purpose of the TCA cycle is not to make ATP directly (it makes only 1 GTP per turn) but to harvest electrons as NADH and FADH2. Those electron carriers then deliver their electrons to the electron transport chain, which does the real ATP-making work via oxidative phosphorylation. Every pathway in this chapter exists to feed electrons to the ETC.
Waterfall with Turbines
Think of the ETC as a waterfall with turbines. Electrons fall from high energy (NADH) to low energy (O2) through four complexes. Each drop pumps protons across the inner mitochondrial membrane. Protons flowing back through ATP synthase spin the enzyme like a waterwheel, synthesizing ATP.
