Lipid metabolism
Introducido| English | Significado |
|---|---|
| β-oxidation | Each cycle gives acetyl-CoA + FADH₂ + NADH. |
| lipoprotein | lipoprotein |
| chylomicron | chylomicron |
| ketone bodies | ketone bodies |
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.
Dificultad 3/5 · 200 monedas + un pequeño bono en el primer intento de hoy
Oxidation, hydration, oxidation, cleavage; the chain comes out 2 carbons shorter and the cycle repeats.
How many β-oxidation cycles does stearate (C18) need?
Dificultad 2/5 · 140 monedas + un pequeño bono en el primer intento de hoy
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?
Dificultad 2/5 · 140 monedas + un pequeño bono en el primer intento de hoy
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.
Dificultad 2/5 · 140 monedas + un pequeño bono en el primer intento de hoy
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?
Dificultad 1/5 · 100 monedas + un pequeño bono en el primer intento de hoy
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?
Dificultad 1/5 · 100 monedas + un pequeño bono en el primer intento de hoy
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.
Dificultad 1/5 · 100 monedas + un pequeño bono en el primer intento de hoy
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.