Makindo Medical Notes

Related Subjects: |Fat Metabolism |Glucose Metabolism |Protein metabolism |Glycolysis Krebs Electron Transport Chain |Alcohol Metabolism |Protein metabolism |Protein Synthesis |Amino acids |Human Metabolism |Carbohydrates |Hydrogen and other Bonds

🥓 Overview of Fat Metabolism

Fat metabolism = digestion, transport, storage, breakdown, and synthesis of lipids. It underpins energy homeostasis, allowing the body to switch from carbohydrates to triglycerides during fasting or exercise. Fats are the most energy-dense macronutrient (~9 kcal/g vs 4 kcal/g for carbohydrate or protein).

🍽️ Digestion & Absorption

• 🔪 Pancreatic lipase breaks triglycerides → free fatty acids + monoglycerides.
• 🫧 Bile salts emulsify fats into micelles for absorption by enterocytes.
• 🚚 Re-esterified triglycerides packaged into chylomicrons → lymphatics → blood.

🚚 Transport of Lipids

• Chylomicrons – dietary triglycerides & cholesterol → tissues.
• VLDL – hepatic triglycerides → tissues.
• LDL – delivers cholesterol to cells (atherogenic).
• HDL – reverse cholesterol transport → liver.
• 💡 Lipoprotein lipase hydrolyses TG in chylomicrons/VLDL → free fatty acids for storage or oxidation.

🔥 Mobilisation of Stored Fat

• Fasting/exercise → ↓ insulin, ↑ glucagon & adrenaline.
• ➡️ Activates hormone-sensitive lipase in adipocytes.
• Releases free fatty acids (bound to albumin) + glycerol (to liver for gluconeogenesis).

⚙️ β-Oxidation of Fatty Acids

• Fatty acids activated → acyl-CoA.
• 🚪 Carnitine shuttle (CPT-I, translocase, CPT-II) moves long-chain FA into mitochondria.
• Cycle: dehydrogenation (FADH₂), hydration, dehydrogenation (NADH), thiolysis → acetyl-CoA.
• ⚡ Acetyl-CoA → TCA cycle; NADH/FADH₂ → ETC. One palmitate (16C) yields ~106 ATP!

🍐 Ketogenesis

• Occurs in liver during prolonged fasting, uncontrolled diabetes, or low-carb diet.
• Excess acetyl-CoA → ketone bodies (acetoacetate, β-hydroxybutyrate, acetone).
• 🧠 Brain & muscle use ketones when glucose is scarce. Excess → ketoacidosis.

🏭 Fatty Acid Synthesis (Lipogenesis)

• Fed state, excess acetyl-CoA exported (via citrate shuttle) to cytoplasm.
• Acetyl-CoA carboxylase → malonyl-CoA (committed step).
• Fatty acid synthase → palmitate (16C). Can be elongated/desaturated.
• Stored as triglycerides in adipose tissue.

⚖️ Regulation

• 🧪 Insulin → ↑ lipogenesis, ↓ lipolysis.
• ⚡ Glucagon & adrenaline → ↑ lipolysis & β-oxidation.
• 🔋 AMPK → energy sensor: promotes catabolism, suppresses synthesis.

⚠️ Clinical Relevance

• 🩸 Diabetes Mellitus – uncontrolled lipolysis & ketogenesis → diabetic ketoacidosis (DKA).
• ⚖️ Obesity – chronic energy surplus → ↑ triglyceride storage, insulin resistance, NAFLD.
• 💉 Hyperlipidaemia – ↑ LDL/VLDL → atherosclerosis & CVD risk.
• 🧬 Carnitine deficiency – impaired β-oxidation → hypoketotic hypoglycaemia.

📌 Summary

Fat metabolism balances storage 🥓 and use 🔥. Key processes: digestion, transport, β-oxidation, ketogenesis, and fatty acid synthesis. Hormones (insulin, glucagon, adrenaline) orchestrate this. Dysregulation contributes to obesity, diabetes, fatty liver, and cardiovascular disease.