Lipid Metabolism: Beta-Oxidation, Ketogenesis, Cholesterol and Lipoproteins
What this domain tests
Lipid metabolism questions test fatty acid activation and beta-oxidation, ketone body formation, cholesterol synthesis, and lipoprotein transport.
Core rules
- Fatty acid activation to fatty acyl-CoA costs 2 ATP equivalents. Long-chain acyl-CoA enters mitochondria via the carnitine shuttle; CPT1 is rate-limiting.
- Each beta-oxidation cycle removes two carbons as acetyl-CoA and yields 1 FADH2 and 1 NADH. Even-chain saturated fatty acids are simplest; odd-chain acids give propionyl-CoA, and unsaturated acids need extra isomerase or reductase steps.
- Ketogenesis occurs in liver mitochondria from acetyl-CoA. HMG-CoA synthase and HMG-CoA lyase form acetoacetate, which is reduced to beta-hydroxybutyrate or decarboxylated to acetone. The liver makes ketones but cannot use them because it lacks CoA transferase.
- Cholesterol synthesis starts from acetyl-CoA; HMG-CoA reductase is the rate-limiting enzyme and the statin target.
- Lipoproteins: chylomicrons carry dietary triacylglycerol; VLDL carries endogenous triacylglycerol; LDL delivers cholesterol; HDL performs reverse cholesterol transport.
Worked example
Palmitate (C16) undergoes 7 beta-oxidation cycles, giving 8 acetyl-CoA, 7 FADH2, and 7 NADH. Activation costs 2 ATP. Using older school values (acetyl-CoA 12, FADH2 2, NADH 3), ATP = 8(12) + 7(2) + 7(3) - 2 = 129. Using modern values (10, 1.5, 2.5), ATP = 80 + 10.5 + 17.5 - 2 = 106. State the convention you use.
Traps
Beta-oxidation does not produce ATP directly; it produces reduced coenzymes and acetyl-CoA. The liver cannot use ketone bodies. LDL is not 'good cholesterol'; HDL is associated with reverse transport. Cholesterol is not a dietary essential in the strict sense because it can be synthesized.