Bioenergetics and glycolysis
แนะนำใหม่| English | ความหมาย |
|---|---|
| glycolysis/ɡlaɪˈkɒləsɪs/ | The oldest way to make ATP, used by almost every living cell, and the anchor of everything later in this course. |
| coupled reactions/ˈkʌpld rɪˈækʃnz/ | coupled reactions |
| phosphofructokinase-1 | phosphofructokinase-1 |
| lactate dehydrogenase | lactate dehydrogenase |
Paying in ATP
- Cells pay for everything in ATP, and the exchange rate is exact: a reaction runs only if the total free-energy change is downhill.
- Glycolysis is the oldest way to make ATP, used by almost every living cell, and the anchor of everything later in this course.
Coupled reactions
- An uphill reaction can run if it is joined to a downhill one: the $\Delta G$ values add. These are coupled reactions 偶联反应.
- ATP → ADP + Pi gives $\Delta G^{\circ\prime} = -30.5$ kJ per mol, enough to drive many uphill steps.
A reaction has ΔG°′ = +14.2 kJ per mol. It is coupled to ATP hydrolysis (−30.5 kJ per mol). What is the overall ΔG°′, in kJ per mol?
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+14.2 + (−30.5) = −16.3 kJ per mol: negative, so the coupled pair runs.
Glycolysis in one line
- Glycolysis 糖酵解 splits one glucose (6 C) into two pyruvate (3 C). The investment phase spends 2 ATP; the payoff phase makes 4 ATP and 2 NADH.
- Net: 2 ATP and 2 NADH per glucose, with or without oxygen.
What is the net yield of glycolysis per glucose?
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Invest 2, earn 4: net 2 ATP, plus 2 NADH. The same with or without oxygen.
Three one-way gates
- Three steps are strongly downhill ($\Delta G^{\circ\prime}$ in kJ per mol): hexokinase (−16.7), phosphofructokinase-1 磷酸果糖激酶-1 (PFK-1, −14.2) and pyruvate kinase (−31.4).
- Only these three are effectively one-way, so only they can be control points. The other seven steps run both ways.
Put these glycolysis enzymes in pathway order.
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Hexokinase traps glucose, PFK-1 commits it, aldolase splits the 6-carbon sugar in two, and pyruvate kinase makes the last ATP.
Why PFK-1 is the gate
- Hexokinase is too early (other pathways use its product) and pyruvate kinase is too late (the investment is spent). PFK-1 is the first step that belongs only to glycolysis.
- AMP and ADP switch it on; ATP and citrate switch it off; fructose-2,6-bisphosphate (an insulin signal) switches it on strongly. One enzyme reads the cell's whole energy state.
Which signal switches PFK-1 off?
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Plenty of ATP and citrate means energy is plentiful, so the gate closes; AMP, ADP and fructose-2,6-bisphosphate open it.
Without oxygen
- Glycolysis needs NAD⁺. Without O₂, lactate dehydrogenase 乳酸脱氢酶 turns pyruvate + NADH into lactate + NAD⁺.
- Lactate is not waste: making it keeps NAD⁺ available so glycolysis, and its 2 ATP, can continue.
Without oxygen, glycolysis would stop if pyruvate were not turned into lactate.
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Glycolysis needs NAD⁺ at one step. Lactate dehydrogenase makes NAD⁺ from NADH; without it the NAD⁺ runs out and glycolysis stops.
Worked example: the ATP ledger
- Per glucose: −2 (investment) + 4 (payoff) = net 2 ATP, plus 2 NADH. With O₂, those NADH are worth about 5 ATP (malate shuttle) or 3 (glycerol phosphate shuttle).
- Without O₂ the 2 NADH are spent turning pyruvate into lactate, so the yield is exactly 2 ATP.
Glucose from glycogen enters glycolysis as glucose-1-phosphate, so the hexokinase step is skipped. What is the net anaerobic ATP yield per glucose unit?
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The phosphate comes from the bond broken in glycogen, not from ATP, so only 1 ATP is invested: 4 − 1 = 3.
Worked example: the gate that will not open
- (Fictional patient) Muscle cramps within seconds of sprinting, and blood lactate does not rise. Glycogen breaks down normally, but muscle PFK-1 is missing.
- Sugar phosphates pile up before the gate, the payoff never comes, ATP falls and myoglobin leaks into the urine. One gate, one exercise syndrome.
Why does blood lactate fail to rise when a patient lacking muscle PFK-1 sprints?
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Lactate comes from pyruvate, which lies past the gate. A block at PFK-1 means no pyruvate and no lactate.
Three common slips
- Gross for net. Glycolysis makes 4 ATP but spends 2: the net is 2.
- Control at reversible steps. Regulation sits at the three one-way gates.
- "Lactate is waste." It is how the cell gets NAD⁺ back without oxygen.
Match each gate enzyme to its ΔG°′ (kJ per mol).
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All three are strongly downhill and effectively one-way, which is why they are the control points.
Recap
- Glucose → 2 pyruvate: net 2 ATP + 2 NADH.
- Three one-way gates; PFK-1 is the committed step: AMP and ADP on, ATP and citrate off.
- Without O₂, lactate regenerates NAD⁺ and the yield is 2 ATP.