Lipid metabolism
Introduced| English | Meaning |
|---|---|
| β-oxidation | The mitochondrial pathway that cuts fatty acids two carbons at a time into acetyl-CoA, making NADH and FADH2 each round. |
| lipoprotein | A particle of lipid wrapped in protein and phospholipid that carries fats in the blood. |
| chylomicron | A large lipoprotein made by gut cells that carries dietary fat through the lymph into the blood. |
| ketone bodies | Acetoacetate and β-hydroxybutyrate, made by the liver from fat in fasting as brain fuel. |
A warehouse with a traffic problem
- Fat is the body's long-term energy store: about 9 kcal per g, against 4 for sugar or protein.
- But lipids do not dissolve in water, so they need a transport fleet, and failures of that fleet underlie the world's commonest killer, heart disease.
β-oxidation
- In mitochondria, β-oxidation β氧化 trims a fatty acyl-CoA 2 carbons at a time. Each cycle gives 1 acetyl-CoA + 1 FADH₂ + 1 NADH.
- Four steps repeat: oxidation (makes FADH₂), adding water, a second oxidation (makes NADH), then cutting off acetyl-CoA. Activating the fatty acid first costs 2 ATP-equivalents.
Put one cycle of β-oxidation in order.
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Oxidation, hydration, oxidation, cleavage; the chain comes out 2 carbons shorter and the cycle repeats.
How many β-oxidation cycles does stearate (C18) need?
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18/2 − 1 = 8 cycles, giving 9 acetyl-CoA: the last cycle splits a 4-carbon piece into two acetyl-CoA.
Worked example: the palmitate count
- Palmitate (C16) needs $16/2 - 1 = 7$ cycles: 8 acetyl-CoA + 7 FADH₂ + 7 NADH.
- $8\times10 + 7\times1.5 + 7\times2.5 - 2 = 80 + 10.5 + 17.5 - 2 = 106$ ATP. Glucose gives 32: per carbon, fat pays more because it is almost fully reduced.
Using 10 ATP per acetyl-CoA, 1.5 per FADH₂, 2.5 per NADH and 2 for activation, how many ATP does stearate (C18) give?
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9 × 10 + 8 × 1.5 + 8 × 2.5 − 2 = 90 + 12 + 20 − 2 = 120 ATP.
The lipoprotein fleet
- Lipoproteins 脂蛋白 carry fat in blood. Chylomicrons 乳糜微粒 bring dietary fat from the gut; VLDL carries fat made in the liver to tissues.
- LDL delivers cholesterol to tissues (the "bad" carrier when high); HDL brings cholesterol back to the liver (the "good" one).
Match each lipoprotein to its route.
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Chylomicrons and VLDL deliver fat; as they lose it, VLDL becomes LDL; HDL runs the return trip.
Worked example: ketones, the brain's backup fuel
- In a long fast, acetyl-CoA from β-oxidation outruns the TCA cycle, because oxaloacetate is being used for gluconeogenesis. The liver turns it into ketone bodies 酮体: acetoacetate and β-hydroxybutyrate.
- They dissolve in blood and reach the brain, each β-hydroxybutyrate worth about 21.5 ATP. By day 3 they give about a third of the brain's energy, after weeks up to two-thirds, sparing muscle protein.
Why does the liver make ketone bodies in a long fast?
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With oxaloacetate used to make glucose, acetyl-CoA cannot all enter the TCA cycle, so the liver packages it as ketones for export.
Worked example: the engine without a spark
- (Fictional infant) Low blood glucose after fasting, with no ketones. An acyl-CoA dehydrogenase (MCAD) is missing, so β-oxidation stalls.
- No acetyl-CoA means no ketones, and too little ATP and acetyl-CoA to drive gluconeogenesis. Low glucose with low ketones points straight to a fat-burning defect.
An infant has low glucose and low ketones after fasting. Which defect fits best?
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Stalled β-oxidation gives no ketones and weak gluconeogenesis: both findings from one break. Type 1 diabetes and excess glucagon raise glucose and ketones.
Three common slips
- Forgetting activation. Subtract 2 ATP-equivalents for each fatty acid.
- "The brain runs on fatty acids in a fast." It oxidises very little fatty acid; ketones are its substitute.
- "LDL is cholesterol." LDL is the carrier particle; cholesterol is part of its cargo.
In a long fast, the brain gets most of its energy by burning long-chain fatty acids directly.
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The brain oxidises very little fatty acid. It uses glucose and, as the fast goes on, ketone bodies made by the liver.
Recap
- β-oxidation: each cycle gives acetyl-CoA + FADH₂ + NADH; palmitate gives 106 ATP.
- Chylomicrons and VLDL deliver fat; LDL delivers cholesterol; HDL returns it.
- In a fast, the liver exports ketones for the brain.