Fatty Acids and Triacylglycerols
High-Yield Summary
- Fatty acids: named by carbon count:double-bond count (e.g., 18:0). Saturated (no double bonds) pack tightly, solid at room temp; unsaturated (has double bonds) are liquid. Linoleic acid (omega-6) and alpha-linolenic acid (omega-3) are essential — diet-only.
- Triacylglycerols (3 fatty acids + glycerol, condensation reaction) store energy efficiently: fatty acid carbons are more reduced than sugar carbons (more energy per carbon), and they're hydrophobic (no water weight).
- Fatty acid synthesis (cytoplasm, high insulin/energy): citrate shuttle moves acetyl-CoA out of mitochondria → acetyl-CoA carboxylase makes malonyl-CoA (rate-limiting, needs biotin) → fatty acid synthase builds palmitate 2 carbons at a time (condensation-reduction-dehydration-reduction, using NADPH).
- Beta-oxidation (mitochondria, low insulin/fasting): fatty acyl-CoA synthetase activates the fatty acid → carnitine shuttle moves it into the matrix → repeating oxidation-hydration-oxidation-cleavage cycle releases acetyl-CoA + NADH + FADH₂ each round.
- Malonyl-CoA links the two pathways — it inhibits carnitine acyltransferase I, preventing simultaneous synthesis and oxidation.
- Odd-chain fatty acids end beta-oxidation with propionyl-CoA → methylmalonyl-CoA (biotin) → succinyl-CoA (vitamin B12-dependent mutase), entering the TCA cycle. Unsaturated fatty acids need extra enzymes (enoyl-CoA isomerase; 2,4-dienoyl-CoA reductase for polyunsaturated) to fix cis double bonds.
Key Terms
- Citrate shuttle
- Moves acetyl-CoA from mitochondria to cytoplasm as citrate, for fatty acid synthesis.
- Acetyl-CoA carboxylase
- Rate-limiting enzyme of fatty acid synthesis; makes malonyl-CoA using biotin, ATP, CO2.
- Fatty acid synthase
- Multi-enzyme complex building fatty acid chains 2 carbons at a time on ACP, using NADPH.
- Carnitine shuttle
- Moves fatty acyl groups into the mitochondrial matrix for beta-oxidation.
- Propionyl-CoA
- 3-carbon product of the last cycle of odd-chain fatty acid beta-oxidation; converted to succinyl-CoA.
Fatty Acid Synthase Cycle (repeats to build the chain)
- 1Condensation: acetyl + malonyl groups join to a 4-carbon molecule, CO2 released
- 2Reduction: NADPH reduces the molecule
- 3Dehydration: water removed, double bond forms
- 4Reduction: second NADPH saturates the segment
Beta-Oxidation Cycle (repeats, removes 2 carbons each round)
- 1Oxidation: forms a double bond
- 2Hydration: water added across the double bond
- 3Oxidation: hydroxyl → carbonyl (beta-ketoacid)
- 4Cleavage: splits into shorter acyl-CoA + acetyl-CoA (also yields 1 NADH + 1 FADH₂ per round)
Synthesis vs. Beta-Oxidation
| Feature | Synthesis vs. Beta-Oxidation |
|---|---|
| Location | Cytoplasm / Mitochondrial matrix |
| Trigger | High insulin, energy abundant / Low insulin, fasting |
| Rate-limiting enzyme | Acetyl-CoA carboxylase (malonyl-CoA) / Carnitine acyltransferase I (shuttle entry) |
| Key cofactor | NADPH (reducing power) / NAD⁺, FAD (oxidizing) |
| Linked by | Malonyl-CoA inhibits the other pathway's carnitine shuttle |
Common MCAT Trap
- Fatty acid synthesis uses NADPH; beta-oxidation produces NADH/FADH₂ — opposite electron-carrier directions, easy to mix up.
- Even-chain fatty acids yield only acetyl-CoA (dead end for gluconeogenesis); odd-chain fatty acids' last round yields propionyl-CoA, which CAN enter gluconeogenesis via succinyl-CoA.
- Malonyl-CoA inhibiting carnitine acyltransferase I is the key coordination point — high malonyl-CoA (active synthesis) shuts off oxidation, and vice versa.
Quick Recall
What is the rate-limiting, committed step of fatty acid synthesis?
What three products does each beta-oxidation cycle release?
How does malonyl-CoA prevent synthesis and oxidation from running simultaneously?
What vitamin does methylmalonyl-CoA mutase require?