Lipoprotein Transport - Lecture 1

Lipoprotein Transport - Lecture 1

Abbreviations and Terms

  • C: Cholesterol
  • CE: Cholesterol Esters
  • FFA: Free Fatty Acids
  • FA: Fatty Acids
  • MTTP (or MTTA): Microsomal Triglyceride Transfer Protein
  • TAG: Triglycerides or Triacylglycerol
  • ACAT: Acyl-CoA Cholesterol Acyltransferase (catalyzes C+FA→CEC + FA \rightarrow CE)

Introduction to Lipoproteins

  • Lipoproteins are particles in the plasma containing lipid and protein components.
  • They transport fat-soluble substances in the blood (a polar environment).
  • They carry triglycerides (TAG), fat-soluble vitamins (A, D, E, K), cholesterol, and cholesterol esters.

Cholesterol

  • Cholesterol is amphipathic due to the presence of a polar hydroxyl (OH) group.
  • Cholesterol Esters are nonpolar because the OH group is replaced with a fatty acid.

Lipoprotein Particle Organization

  • Core: Lipophilic (nonpolar), containing TAG and cholesterol esters.
  • Outer Coat: Amphipathic molecules (free cholesterol, phospholipids, apolipoproteins) with nonpolar ends inward and polar ends outward.

Types of Lipoproteins

Chylomicrons
  • Largest lipoprotein particles.
  • Assembled in the gut from absorbed lipids (TAG, cholesterol, cholesterol esters, fat-soluble vitamins).
  • Primarily composed of triglycerides.
  • Function: Transport dietary triglycerides to tissues.
  • As they deliver triglycerides, they decrease in size and increase in density.
Very Low-Density Lipoproteins (VLDL)
  • Assembled in the liver.
  • Function: Transport triglycerides to tissues.
  • Smaller and denser than chylomicrons, with a higher proportion of protein, cholesterol esters, and phospholipids.
  • As VLDL delivers triglycerides, it becomes smaller and denser.
Intermediate-Density Lipoproteins (IDL)
  • VLDL remnants that have lost a significant amount of triglyceride.
  • Higher density than VLDL.
  • Represent an intermediate stage in VLDL metabolism.
Low-Density Lipoproteins (LDL)
  • Assembled in the liver.
  • Smaller and denser than IDL.
  • Primary function: Transport cholesterol to tissues.
  • Contain some triglycerides but primarily carry cholesterol.
High-Density Lipoproteins (HDL)
  • Smallest and densest lipoprotein particles.
  • High protein and phospholipid content, with very little triglyceride.
  • Function: Pick up cholesterol and cholesterol esters from tissues and transport them to the liver or other tissues.

Trends Among Lipoproteins

  • As you go from chylomicrons to VLDL to IDL to LDL to HDL:
    • Diameter decreases.
    • Density increases.
    • Protein, cholesterol ester, and phospholipid percentage increases.
    • Triglyceride percentage decreases.

Composition of Lipoproteins

  • Chylomicrons: Primarily triglycerides (83-84% on average, up to 90+% when freshly assembled).
  • The relative percentages of components change as lipoproteins deliver their contents.

Chylomicron Formation

  • In the intestinal lumen, triglycerides are broken down into fatty acids by lipase and co-lipase.
  • Fatty acids and cholesterol are absorbed into intestinal cells.
  • Cholesterol can be esterified to form cholesterol esters.
  • Plant sterols are removed via ABCG5/ABCG8 transporters.
  • Cholesterol esters, triglycerides, and ApoB48 are packaged into chylomicrons.
  • Chylomicrons are released into the lymphatic circulation.

Identifying Lipoproteins in Blood Samples

  • After a blood sample stands overnight at 4°C, chylomicrons form a white layer at the top due to their low density and large size (reflecting light).
  • Normal to have chylomicrons 3-4 hours after a meal (longer after a greasy meal).
  • If chylomicrons are present 12 hours after a meal, it may indicate lipoprotein lipase deficiency (1 in a million) or ApoC2 deficiency (1 in a million).

VLDL Metabolism

  • Chylomicrons are packaged in the gut and contain ApoB48.
  • VLDL is packaged in the liver and contains ApoB100.
  • Both transport TAG to tissues (adipose and muscle).
  • The liver obtains TAG from:
    • Chylomicron and VLDL remnants.
    • De novo synthesis from free fatty acids.
    • Excess carbohydrate or protein converted to TAG.
    • Alcohol metabolism (acetyl-CoA converted to TAG).

Identifying VLDL in Blood Samples

  • High levels of VLDL in a blood sample cause the serum to appear turbid or cloudy, as they are the same density as blood and remain in suspension.