Lipoprotein and Cholesterol Metabolism

• Unlike starch, dietary fat comes in many different forms
• Fat needs to be made into an emulsion for digestion
• Fat needs to be carried around the bloodstream within lipoproteins
• Emulsions are formed using amphiphilic/amphipathic molecules
• Amphiphilic molecules act as detergents to emulsify fats into small particles and form micelles
• Bile salts are made from cholesterol in the liver through addition of polar groups
• Bile salts are stored in the gall bladder, which contracts after a meal to secrete bile salts into the small intestine
• After digestion of fats, 90% of bile salts are reabsorbed and taken back to the liver via the hepatic portal vein while the remainder is disposed through faeces
• The production of bile salts is the only way that cholesterol is metabolised and disposed
• In the small intestine, dietary fats are churned with bile salts, causing fat to become contained within the core of micelles
• Pancreatic lipase hydrolyses fat into FAs and glycerol which can be absorbed by cells
• The bile duct can become blocked by gall stones, meaning that fat isn't digested as bile salts cannot be secreted
• Some inhibitors of fat digestion have been developed as weight-loss drugs
• Orlistat inhibits pancreatic lipase
• Olestra is a fat substitute consisting of FA attached to sucrose which cannot be digested by lipase
• After absorption into the intestinal mucosa, fats are packaged in lipoproteins for transport around the body
• Lipoproteins:

  • Phospholipid monolayer
  • Hydrophobic centre
  • Studded with apoproteins
• Apoproteins have a role as enzymes and allow cells to recognise the micelle and its contents
• • There are different types of lipoproteins
  • Size
  • Internal composition
  • Types of apoproteins
• Cholesterol isn't completely hydrophobic due to having one slightly polar end
• Cholesterol must become esterified to make it completely hydrophobic to be transported in the core of lipoproteins
• How is cholesterol esterified for transport in lipoproteins?

  esterifying a FA to the hydrophilic end of cholesterol
• Chylomicrons are the first lipoproteins made by intestinal cells
• Chylomicrons are large and low density
• Chylomicrons contain fat and dietary cholesterol
• Chylomicrons enter the lymphatic system
• What has the last exposure to chylomicrons?

  The liver
• In the blood, chylomicrons interact with lipoprotein lipase (LPL) on the surface of cells
• Expression of LPLs is stimulated by insulin
• The fat from the chylomicron is hydrolysed by LPLs
• After fat has been removed from chylomicrons, cholesterol rich remnants are left behind
• Chylomicron remnants are endocytosed by the liver
• The liver assembles Very Low Density Lipoproteins (VLDL) from:

  1. fat and cholesterol esters returned from remnants
  2. fat produced from lipogenesis
• VLDL is excreted into the bloodstream
• LPL in the peripheral tissues removes fats from VLDL
• When fat is removed from VLDL, it forms IDL
• When more fat is removed from IDLs, it makes LDLs
• Both IDL and LDL can be endocytosed by the liver
• Tissues take up LDL through LDL receptors in an endocytotic process
• How is dietary cholesterol delivered to tissues?

  LDL