lipid metabolism

• What are the major steps of lipid digestion and absorption after a meal?

  The major steps include emulsification of fats by bile salts, enzymatic breakdown by lipase, formation of micelles, diffusion of lipids into absorptive cells, reassembly of triglycerides, and transport of chylomicrons to the lymphatic system and liver.
• What are the functions of the enzymes and hormones involved in lipid digestion and absorption?

  • Lipases: Enzymes that break down lipids
  • Secretin: A hormone that stimulates the pancreas to secrete pancreatic juice
  • Cholecystokinin (CCK): A hormone that stimulates the gallbladder to release bile and the pancreas to secrete pancreatic juice
  • Pancreatic juice: Contains digestive enzymes (including pancreatic lipase) and bicarbonates (HCO₃)
• What is the function of bile salts?

  Bile salts emulsify lipids to aid in lipid digestion.
• What is the function of pancreatic lipase?

  Pancreatic lipase removes two fatty acids from each triglyceride molecule during digestion.
• In which digestive organ does the majority of lipid absorption occur?

  The small intestine.
• What are micelles and how are they involved in lipid absorption?

  • Micelles: Water-soluble spherical lipid clusters
  • Contents: Long-chain fatty acids, cholesterol, monoglycerides, phospholipids, and fat-soluble vitamins
  • Function: Allow lipids to be suspended in digestive juices and facilitate diffusion into absorptive cells
• What are chylomicrons and what is their function?

  Chylomicrons are lipoproteins that transport lipids through the bloodstream after lipids are reassembled into triglycerides, along with cholesterol and phospholipid fragments coated with protein.
• How are short-chain and medium-chain fatty acids absorbed?

  They diffuse into the absorptive cells of the villi and enter the bloodstream through the portal vein.
• How are long-chain fatty acids absorbed?

  They are packed into chylomicrons and enter the lymphatic system.
• What is fat malabsorption and what are its symptoms?

  Fat malabsorption is impaired fat absorption due to conditions such as lack of lipase, causing steatorrhea and rapid weight loss.
• How are chylomicrons transported to the bloodstream?

  • Chylomicrons pass through the lymphatic system
  • Transported to the thoracic duct
  • Enter the bloodstream via the left subclavian vein
• What happens to chylomicrons after they enter the bloodstream?

  • Circulate to target tissues
  • Broken down by lipoprotein lipase (LPL) into monoglycerides and free fatty acids
  • Components picked up by nearby cells for energy
  • Chylomicron remnants rich in cholesterol travel to the liver
  • Cholesterol processed and utilized in the liver
• What are the functions of Very-low-density lipoprotein (VLDL) and Low-density lipoprotein (LDL) during fasting?

  VLDL carries triglycerides in the bloodstream, and LDL carries cholesterol into tissues; elevated LDL is linked to increased CVD risk.
• What are the functions of High-density lipoprotein (HDL) and how is low HDL related to CVD?

  HDL transports cholesterol away from tissues to the liver for elimination; low HDL is linked to increased CVD risk.
• What is enterohepatic circulation of bile and how does it influence blood cholesterol levels?

  • Enterohepatic circulation: Recyles bile salts by incorporating them into new bile
  • Impact: Interfering with cholesterol and bile absorption, reducing blood cholesterol levels
• What are gallstones and what are some strategies to reduce their formation?

  • Gallstones: Hard particles accumulating in the gallbladder or bile ducts
  • Cholecystectomy: Surgical removal of a diseased gallbladder
  • Prevention strategies:
  • Eat smaller, more frequent meals
  • Avoid high-fat meals
• What do gallstones usually consist of?

  Cholesterol.
• How are fats stored and broken down for energy production?

  • Fats stored in adipocytes as triglycerides
  • Hormone sensitive lipase (HSL): Removes three fatty acids from a triglyceride
  • Lipolysis: Breakdown of fats facilitated by HSL
  • Fatty acids taken up by cells when ATP is needed
  • Undergo catabolism in the mitochondria
  • Only cells with mitochondria can utilize fatty acids
• How are fatty acids activated to enter beta-oxidation?

  Fatty acids are activated by binding to $coenzyme A$ in the cytoplasm.
• What molecule helps fatty acids pass through the mitochondrial membranes?

  Carnitine.
• What is beta-oxidation and what are its major products?

  • Beta-oxidation: Chemical pathway involved in the catabolism of activated fatty acids
  • Process: Cleaves fatty acids into two-carbon segments converted into $acetyl CoA$
  • $acetyl CoA$ enters the citric acid cycle
• What is ketogenesis and what are the main ketone bodies produced?

  • Ketogenesis: Formation of ketone bodies
  • Main ketone bodies:
  • Acetoacetate
  • β-hydroxybutyrate
  • Acetone
  • Produced in the liver when there is excess $acetyl CoA$
• What is a ketogenic diet and what are its effects?

  • Ketogenic diet: High-fat, high-protein, low-carbohydrate diet
  • Ketosis: Formation of excess ketone bodies as a result of the diet
  • Effects:
  • Loss of appetite
  • Used to treat epilepsy
• What is ketoacidosis and what are its symptoms?

  • Ketoacidosis: Condition where excess acetoacetate and β-hydroxybutyrate lower blood pH
  • Symptoms:
  • Potentially life-threatening
  • Excessive thirst
  • Frequent urination
  • Blood glucose > 250 mg/dL
  • “Fruity” odor to breath
  • Can lead to coma and death if untreated
• About how much of total daily energy intake do people in the UK obtain from fat?

  35%.
• What percentage of total daily energy intake in the UK population comes from saturated fat?

  14%.
• What percentage of total daily energy intake in the UK population comes from monounsaturated fat?

  12.5%.
• What percentage of total daily energy intake in the UK population comes from omega-3 polyunsaturated fats?

  1%.
• What are the dietary fat and cholesterol recommendations?

  • Total fat: No more than 35% of total calories
  • Saturated fat: Less than 11% of total calories
  • Trans fat: Keep intake as low as possible (< 2%)
  • Polyunsaturated fat (PUFA): Around 6.5% of total calories with emphasis on omega-3 FA
  • Emphasize foods rich in PUFA and MUFA (e.g., fish, nuts, vegetable oils)
  • Emphasize foods low in saturated fat (e.g., low-fat milk, lean meat cuts)
• What is cardiovascular disease (CVD) and what diseases does it include?

  • Cardiovascular disease (CVD): Group of diseases affecting the heart and blood vessels
  • Includes:
  • Coronary artery disease
  • Stroke
  • Disease of the blood vessels
• What is atherosclerosis?

  Atherosclerosis is a long-term disease process in which plague builds up inside arterial walls.
• What is arteriosclerosis?

  Arteriosclerosis is a condition resulting from atherosclerosis characterized by loss of arterial flexibility.
• How does atherosclerosis develop after arterial lining injury?

  • Arterial lining becomes inflamed
  • White blood cells become laden with oxidized $LDL$ particles
  • Arterial plaque forms, interfering with circulation
  • Clots become more likely to form
• What is a thrombus and how can it lead to myocardial infarction and stroke?

  • Thrombus: Fixed bunch of clots disrupting blood flow
  • Effects:
  • Partially closes off artery’s lumen
  • Bouts of chest pain if in the heart
  • Myocardial infarction (heart attack): Complete blockage of blood flow to heart muscle, causing muscle death
  • Stroke: Blockage of an artery in the brain, causing nourished brain cells to die
• How can atherosclerosis in the carotid arteries cause a stroke?

  Atherosclerosis in the carotid arteries can reduce blood flow, and clots forming there can travel to the brain, triggering a stroke.
• What is an embolus?

  An embolus is a thrombus or part of a plaque that breaks free and travels through the bloodstream.
• What are the major risk factors for developing atherosclerosis?

  • Non-modifiable risk factors:
  • Family history of CVD (especially before 60 years of age)
  • Increasing age
  • Male sex
  • Race/ethnic background
  • Modifiable risk factors:
  • Unhealthy diet
  • Physical inactivity
  • Smoking
  • Excess body fat
  • Elevated blood cholesterol (especially LDL cholesterol)
  • Hypertension
  • Diabetes mellitus
  • Untreated sleep apnea
• What is a lipoprotein profile?

  A lipoprotein profile is a series of blood tests evaluating total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride levels to determine atherosclerosis risk.
• How do lipoproteins contribute to atherosclerosis?

  • HDL (good cholesterol):
  • Conveys lipids away from tissues to the liver for elimination
  • Does not contribute to plaque formation
  • LDL (bad cholesterol):
  • Conveys lipids to tissue
  • Small, dense LDL contributes more to atherosclerosis
  • Oxidized LDL:
  • Damaged by free radicals
  • Contributes to atherosclerosis
• What are the classifications of fasting blood lipid levels?

  • Total Cholesterol (mg/dL):
  • < 200: Desirable
  • 200–239: Borderline high
  • ≥ 240: High
  • LDL Cholesterol (mg/dL):
  • < 100: Optimal
  • 100–129: Near optimal/Above optimal
  • 130–159: Borderline high
  • 160–189: High
  • ≥ 190: Very high
  • HDL Cholesterol (mg/dL):
  • < 40 (men); < 50 (women): Low
  • ≥ 40 (men); ≥ 50 (women): Desirable
  • Triglycerides (mg/dL):
  • < 150: Normal
  • 150–199: Borderline high
  • ≥ 200: High