Biochemistry
Chemistry and Metabolism of Lipids
Lipid metabolism for MBBS: beta-oxidation, fatty acid and cholesterol synthesis, ketone bodies, lipoproteins and dyslipidaemia, mapped to NMC codes BI4.2 to BI4.7.
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Chemistry and Metabolism of Lipids
Lipid metabolism for MBBS: beta-oxidation, fatty acid and cholesterol synthesis, ketone bodies, lipoproteins and dyslipidaemia, mapped to NMC codes BI4.2 to BI4.7.
The lipid chapter explains how fats are digested, transported, stored and burned. It covers beta-oxidation and fatty acid synthesis, cholesterol and ketone body metabolism, the lipoproteins and their disorders, and the eicosanoids that link lipids to inflammation and platelet function.
High-yield: Chemistry and Metabolism of Lipids
- Fatty acid beta-oxidation occurs in mitochondria and yields one FADH2, one NADH and one acetyl-CoA per cycle.
- Carnitine palmitoyltransferase-1 shuttles long-chain fatty acids into mitochondria and is the rate-limiting step of beta-oxidation, inhibited by malonyl-CoA.
- Fatty acid synthesis occurs in the cytosol, uses NADPH and requires acetyl-CoA carboxylase, the rate-limiting enzyme, which needs biotin.
- HMG-CoA reductase is the rate-limiting enzyme of cholesterol synthesis and the target of statins.
- Ketone bodies, acetoacetate and beta-hydroxybutyrate, are made in the liver during fasting and used by brain and muscle; the liver cannot use them itself.
- Chylomicrons carry dietary triglyceride, VLDL carries endogenous triglyceride, LDL carries cholesterol to tissues, and HDL brings cholesterol back to the liver.
- Lipoprotein lipase, activated by apolipoprotein C-II, hydrolyses triglyceride in chylomicrons and VLDL at the capillary wall.
- LDL is taken up by the LDL receptor recognising apolipoprotein B-100; its deficiency causes familial hypercholesterolaemia.
- Familial hypercholesterolaemia raises LDL and causes tendon xanthomas, corneal arcus and premature coronary disease.
- Lecithin-cholesterol acyltransferase esterifies cholesterol on HDL for reverse cholesterol transport.
- Essential fatty acids, linoleic and alpha-linolenic acid, cannot be synthesised and must come from the diet.
- Arachidonic acid is the precursor of prostaglandins and thromboxanes via cyclooxygenase and of leukotrienes via lipoxygenase.
- Aspirin irreversibly acetylates cyclooxygenase, reducing thromboxane-driven platelet aggregation.
- A desirable fasting lipid profile keeps LDL below 100 mg/dL, HDL above 40 mg/dL and triglycerides below 150 mg/dL.
- Uncontrolled diabetes drives excess ketogenesis, producing diabetic ketoacidosis with a raised anion gap.
Lipoproteins at a glance
- **Chylomicron:** Carries dietary triglyceride from the gut. Cleared by lipoprotein lipase.
- **VLDL:** Carries endogenous triglyceride from the liver.
- **LDL:** Delivers cholesterol to tissues. Taken up via apolipoprotein B-100.
- **HDL:** Reverse cholesterol transport back to the liver. Protective.
NMC competencies in this chapter
- **BI4.2:** Digestion, absorption and metabolism of dietary lipids
- **BI4.3:** Regulation of lipoprotein metabolism and associated disorders
- **BI4.4:** Structure and functions of lipoproteins and their link with atherosclerosis
- **BI4.5:** Interpretation of laboratory results of lipid analytes
- **BI4.6:** Therapeutic uses of prostaglandins and inhibitors of eicosanoid synthesis
- **BI4.7:** Interpretation of laboratory results of analytes in lipid metabolism
Frequently Asked Questions
What is the rate-limiting step of cholesterol synthesis?
HMG-CoA reductase, which converts HMG-CoA to mevalonate. It is the enzyme that statins competitively inhibit to lower blood cholesterol.
Why can the liver make ketone bodies but not use them?
The liver lacks the enzyme thiophorase (succinyl-CoA acetoacetyl-CoA transferase), so it exports ketone bodies for use by the brain, heart and skeletal muscle during fasting.
What causes familial hypercholesterolaemia?
A defect in the LDL receptor that recognises apolipoprotein B-100, so LDL is not cleared from blood. It leads to very high cholesterol, tendon xanthomas and premature coronary disease.
How does malonyl-CoA link fat synthesis and breakdown?
Malonyl-CoA, the building block of fatty acid synthesis, inhibits carnitine palmitoyltransferase-1. This prevents the cell from making and burning fatty acids at the same time.
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