Lipid metabolism – I: Lipid Digestion, Mobilization and Beta- oxidation Flashcards
(31 cards)
What are the main dietary lipids?
Fatty acids, triacylglycerols (TAGs), phospholipids, cholesterol esters, and glycolipids.
What is the structure of a triacylglycerol?
A glycerol backbone with three fatty acid chains attached at the sn-1, sn-2, and sn-3 positions.
How are triacylglycerols digested in the small intestine?
Bile salts emulsify TAGs into micelles.
Pancreatic lipase removes fatty acids at C1 and C3, producing 2-monoacylglycerol and free fatty acids.
These are absorbed by intestinal epithelial cells and repackaged into chylomicrons.
What is the role of bile salts in lipid digestion?
Synthesized from cholesterol in the liver.
Emulsify dietary lipids into micelles for better enzyme action.
Facilitate absorption of fat-soluble vitamins (A, D, E, K).
What are chylomicrons, and what do they contain?
Lipoprotein particles that transport dietary lipids. They contain:
Apolipoproteins (B-48, C-II, C-III).
Triacylglycerols, cholesteryl esters, and phospholipids.
How are stored fatty acids mobilized from adipose tissue?
Hormones (e.g., glucagon) activate PKA.
PKA phosphorylates perilipin and hormone-sensitive lipase (HSL).
ATGL and HSL sequentially hydrolyze TAG to release fatty acids and glycerol.
What is the role of perilipin in lipolysis?
Blocks lipase access to TAGs under basal conditions.
When phosphorylated by PKA, it releases CGI-58 to activate ATGL, initiating lipolysis.
What are the possible fates of glycerol released during lipolysis?
Released into circulation for transport to other tissues.
Re-esterified into new TAGs.
Converted to glycerol-3-phosphate for glycolysis or gluconeogenesis (liver only).
How are long-chain fatty acids transported into mitochondria for β oxidation?
Via the carnitine shuttle:
Fatty acyl-CoA is converted to fatty acylcarnitine by CPT-I.
Transported across the inner mitochondrial membrane by carnitine translocase.
Converted back to fatty acyl-CoA by CPT-II.
Summarize the four steps of β oxidation for one cycle.
Oxidation: Acyl-CoA dehydrogenase produces FADH₂ and trans-Δ²-enoyl-CoA.
Hydration: Enoyl-CoA hydratase adds H₂O to form L-β-hydroxyacyl-CoA.
Oxidation: β-hydroxyacyl-CoA dehydrogenase produces NADH and β-ketoacyl-CoA.
Cleavage: Thiolase releases acetyl-CoA and a shortened acyl-CoA
What is the net yield of β oxidation for palmitate (C16)?
8 acetyl-CoA.
7 FADH₂.
7 NADH.
How might dysregulation of perilipin contribute to metabolic disorders?
Obesity: Reduced lipolysis leads to excessive fat storage.
Fatty liver disease: Impaired fat mobilization causes lipid accumulation.
Insulin resistance: Altered lipid metabolism disrupts glucose homeostasis.
What enzyme initiates TAG digestion in the small intestine, and what are its products?
Pancreatic lipase (activated by bile salts).
Products: 2-monoacylglycerol + 2 free fatty acids (cleaves C1/C3).
Exam trick: Gastric lipase plays a minor role (10% digestion).
Why are bile salts essential for lipid absorption?
Emulsify large lipid droplets → micelles (↑ surface area for lipases).
Derived from cholesterol (clinical link: gallstones form if bile salts are deficient).
Easy to miss: Also absorb fat-soluble vitamins (A, D, E, K).
What is the fate of chylomicrons after intestinal absorption?
Enter lymphatic system (not portal blood!) → thoracic duct → systemic circulation.
Deliver dietary lipids to adipose tissue, muscle, liver.
Clinical link: ApoC-II on chylomicrons activates lipoprotein lipase (LPL) in capillaries.
A patient with cystic fibrosis has steatorrhea. Why?
Pancreatic duct obstruction → deficient pancreatic lipase/bile salt delivery → undigested TAGs in stool.
Key detail: Treat with pancreatic enzyme replacement (e.g., pancrelipase).
Why does fasting or glucagon release activate HSL in adipocytes?
Glucagon → ↑ cAMP → PKA phosphorylates perilipin/HSL → releases fatty acids for energy.
Clinical link: In diabetes, unopposed HSL activation → ↑ plasma FFA → ketoacidosis.
A patient has muscle weakness and hypoglycemia during fasting. Carnitine deficiency is suspected. Why?
Carnitine shuttle defect → long-chain FAs can’t enter mitochondria → no β-oxidation → energy crisis.
Easy to miss: Medium-chain FAs (C6-C12) bypass this shuttle (treatment: MCT oil).
Why can’t glycerol from lipolysis be used in adipose tissue?
Adipocytes lack glycerol kinase (only liver/kidneys have it).
Exam trick: Glycerol is shipped to the liver for gluconeogenesis/glycolysis.
What’s the rate-limiting step of β-oxidation, and how is it regulated?
Carnitine palmitoyltransferase I (CPT-I) on the outer mitochondrial membrane.
Inhibited by malonyl-CoA (from FA synthesis → prevents futile cycling).
How many ATP are produced from palmitate (C16) β-oxidation?
106 ATP total:
7 FADH₂ → 10.5 ATP (×1.5).
7 NADH → 17.5 ATP (×2.5).
8 acetyl-CoA → 80 ATP (×10 via TCA/ETC).
Subtract 2 ATP for activation (acyl-CoA synthetase).
What happens if HSL is chronically activated (e.g., in obesity)?
↑ FFAs → ectopic fat deposition in liver/muscle → insulin resistance.
Easy to miss: Perilipin dysfunction exacerbates this (reduced lipolysis control).
Mnemonic for β-oxidation enzymes (in order).
Oxidation (acyl-CoA dehydrogenase).
Hydration (enoyl-CoA hydratase).
Oxidation (β-hydroxyacyl-CoA dehydrogenase).
Ketolysis (thiolase).
