Lecture 4.2: Lipid Transport

Question 1

Chylomicron Metabolism

Answer 1

• ApoB-48 is added to chylomicrons (nascent ch.)
  in enterocytes
• Chylomicrons are exocytosed to the lymphatic
  system where they travel to thoracic duct that
  empties into left subclavian vein
• In the blood they acquirea apoCII and apoE
  from HDL (mature ch.)
• ApoCII activates lipoprotein lipase (LPL)
  anchored to the capillary wall of peripheral
  tissues- adipocytes and muscle
• FAs from the break down of TGs enter cells
  depleting chylomicron of its TG content
• ApoCII is returned to HDL and chylomicron
  remnants are removed from blood by liver

Question 2

What happens to Chylomicrons in the Liver?

Answer 2

• apoE binds to its hepatocyte receptors and the
  chylomicron remnants are taken up by
  receptor mediated endocytosis
• In liver, chylomicron remnants fuse with
  lysosomes and their content is degraded
  releasing amino acids, free cholesterol and FAs

Question 3

Main Carriers of TGs (2)

Answer 3

• Chylomicron
• VLDL

Question 4

Main Carriers of Cholesterol Esters (3)

Answer 4

• IDL
• LDL
• HDL

Question 5

VLDL Metabolism

Answer 5

• VLDL is formed in liver for transporting TGs to
  other tissues
• ApoB100 is added during VLDL formation
• Released directly to blood (nascentVLDL)
• ApoCII and apoE are added to VLDL from HDL
  in blood (mature VLDL)
• VLDL binds LPL on muscle and adipose
  releasing FAs andglycerol (leading to formation
  of VLDL remnants)
• Some TGs are transferred to HDL
• Some cholesterol esters are transferred to VLDL

Question 6

Transition of VLDL to IDL

Answer 6

• When VLDL content depletes to ~30%, the
  particle becomes a short-lived IDL particle

Question 7

What 2 things can happen to IDL?

Answer 7

• Taken up by the liver via apoE and processed by
  hepatic triglyceride lipase (HTGL)
• Upon depletion to ~ 10%, IDL loses apoCII and
  apoE and becomes an LDL particle

Question 8

LDL Metabolism

Answer 8

• LDL transports cholesterol to peripheral
  tissues or returns it to liver
• LDL binds to cells expressing LDL receptor
  through apoB-100 and is endocytosed
• High cellular concentration of cholesterol
  decreases de novo synthesis of cholesterol and
  LDL receptor expression

Question 9

What is the effect of defects in the LDL receptor? (2)

Answer 9

• Elevated Blood Cholesterol
• CVD

Question 10

LDL and Clinical Relevance

Answer 10

• Half life of LDL in blood is much longer than that
  of VLDL or IDL
• Making LDL more susceptible to oxidative
  damage
• Oxidised LDL is taken up by macrophages that
  can transform to foam cells
• This contributes to formation of atherosclerotic
  plaques

Question 11

HDL Role

Answer 11

• HDL transports excess cholesterol from
  peripheral tissues to the liver (reverse
  cholesterol transport) for disposal as bile
• Protects from development of atherosclerosis
• HDL is synthesised in liver and intestine

Question 12

HDL Metabolism

Answer 12

• Nascent HDL is disc-shaped and has initially
  only ApoAI, then also apoCII and apoE are
  added
• HDL can also “bud off” from chylomicrons and
  VLDL as they are digested by LPL
• HDL matures by progressively taking up
  cholesterol from peripheral tissues via ABCA1
• Cholesterol is then esterified by LCAT (activated
  by ApoAI) to cholesterol ester which is
  sequestered to the core of HDL causing this
  particle to assume a spherical shape
• CETP transfers some esters to VLDL by
  exchanging TG
• Cholesterol is taken up from tissues and
  returned to liver as esters which are then
  converted to free cholesterol
• SR-B1 in liver uptakes esters from HDL