Beta-oxidation of saturated fatty acids
Fatty acids are broken down in the mitochondria, two carbons at a time, as acetyl-CoA, giving FADH2 and NADH for a large ATP yield.
The steps
Steps A and B happen once. Steps 1–4 repeat, each round cutting 2 carbons off as acetyl-CoA. Palmitate (16 C) needs 7 rounds, because the last round splits a 4-carbon piece into 2 acetyl-CoA. The starred step sets the rate.
- AFatty acid + CoA + ATP → Acyl-CoA + AMP + PPiAcyl-CoA synthetase (thiokinase) · activation, in the cytoplasm at the outer mitochondrial membrane · costs 2 ATP-equivalents
- B★Acyl-CoA → Acyl-carnitine → Acyl-CoA inside the matrixCPT-I, translocase, CPT-II · carnitine shuttle · CPT-I is blocked by malonyl-CoA
- 1Acyl-CoA → trans-Δ2-Enoyl-CoAAcyl-CoA dehydrogenase · oxidation · makes FADH2
- 2Enoyl-CoA → β-Hydroxyacyl-CoAEnoyl-CoA hydratase · hydration · adds water
- 3β-Hydroxyacyl-CoA → β-Ketoacyl-CoAβ-Hydroxyacyl-CoA dehydrogenase · oxidation · makes NADH
- 4β-Ketoacyl-CoA + CoA → Acetyl-CoA + Acyl-CoA (2 C shorter)Thiolase · thiolysis · the shorter acyl-CoA goes back to step 1
★ one-way, controls the pace
Energy count, older books (NADH = 3, FADH2 = 2 ATP)
Energy count, newer books (NADH = 2.5, FADH2 = 1.5 ATP)
Why it matters
- Main fuel for the heart and resting skeletal muscle, and for most tissues during fasting.
- In the liver, surplus acetyl-CoA is turned into ketone bodies.
- The brain and red blood cells do not use fatty acids as fuel (red cells have no mitochondria).
- Short- and medium-chain fatty acids enter the mitochondria without carnitine.
Carnitine is made in the body from lysine and methionine and is also found in meat and milk. FAD comes from riboflavin (B2), NAD+ from niacin (B3), and CoA from pantothenic acid (B5). The medium-chain fats of coconut oil enter mitochondria without carnitine.
10 marks: “Describe the beta-oxidation of palmitic acid with its energetics.” Activation, carnitine shuttle, the 4 repeating steps, 7 cycles, then the ATP count (129 older or 106 newer; say which you use).
5 marks: “Calculate the ATP yield from complete oxidation of palmitate.” 8 acetyl-CoA + 7 FADH2 + 7 NADH = 131 (or 108) ATP, minus 2 for activation = 129 (or 106).
2 marks: “What is the role of carnitine?” It carries long-chain fatty acids across the inner mitochondrial membrane (via CPT-I and CPT-II) for beta-oxidation.
The 4 repeating steps in order: Oxidation, Hydration, Oxidation, Thiolysis. For palmitate: 7 cycles give 8 acetyl-CoA, because the last cycle leaves two.