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LIPID TRANSPORT. DR. TISCHLER. OBJECTIVES. List the lipid components of the diet. Describe the five steps of digestion and absorption of lipids including the important enzymes and location where each step occurs. Describe the general structure of a lipoprotein

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LIPID TRANSPORT

DR. TISCHLER


OBJECTIVES

  • List the lipid components of the diet.

  • Describe the five steps of digestion and absorption of lipids including the important enzymes and location where each step occurs.

  • Describe the general structure of a lipoprotein

  • Name the 4 main classes of lipoproteins and

  • a) indicate whether each is in the exogenous or the endogenous system.

  • b) identify the major lipid component in each.

  • c) describe their lipid-transport functions.

  • d) list their key apoproteins and the functions of these apoproteins


OBJECTIVES

  • Discuss the function of lipoprotein lipase.

  • Outline the steps in the processing of:

  • a) chylomicrons from their synthesis in the intestinal cell to the delivery of cholesterol in chylomicron remnants to the liver.

  • b) VLDL from its synthesis in the liver to the delivery of cholesterol to cells via the low-density-lipoprotein (LDL)receptor including the cellular uptake and processing of cholesterol via LDL.

  • Describe how defects in the LDL receptor are associated with familial hypercholesterolemia and atherosclerosis


  • Fat (lipid) makes up 37% of the calories in the American diet

  • Fat is energy rich and provides 9 kcal/gm

  • Dietary lipids are 90% triacylglycerols, but also include cholesterol esters, phospholipids, essential unsaturated fatty acids and fat soluble vitamins

  • Normally essentially all (98%) of the fat consumed is absorbed, and most is transported to adipose for storage.


Lingual Lipase diet

STEP 1

Gastric Lipase

Figure 1 Five steps of lipid digestion and absorption

Lipids:

Triacylglycerol

Cholesterol esters

Phospholipids

stomach

STEP 2

Pancreas releases:

Lipase (+colipase)

cholesterol esterase

phospholipase A2

small intestine

pancreas

STEP 4

Lipids absorbed from micelles into epithelial cells

STEP 3

Liver releases bile acids to solubilize lipid products in mixed micelles

liver

STEP 5

Chylomicrons form and travel through lymphatics



Figure 2. Model of low density lipoprotein. Other lipoproteins have a similar structure differing in the core content of lipid and the type of apoproteins on the surface of the molecule


Table 2. The major classes of lipoproteins and their relative content of triacylglycerol, cholesterol and protein


chylomicrons acquire apo CII (C) and E (E) from HDL relative content of triacylglycerol, cholesterol and protein

CE

CE

CE

CE

CE

E

CE

CE

E

CE

CE

C

E

C

chylomicron remnants travel to liver

E

C

E

E

E

Liver: apo E on remnants bind receptor

Cholesterol deposited in liver

chylomicron interacts with lipoprotein lipase removing FFA

Lymph system:

INTEST

INE

non-hepatic tissues

ApoB48

helps with chylomicron

LIVER

Figure 3. Exogenous pathway of lipid transport. Chylomicrons carry dietary fatty acids to tissues and remnants take cholesterol to the liver


VLDL acquires apo CII (C) and E (E) from HDL relative content of triacylglycerol, cholesterol and protein

B100 (B) helps assemble and export nascent VLDL

CE

CE

CE

CE

CE

CE

C E

C E

CE

C E

C E

bile acids

LDL travels to tissues

B100 binds to receptors

Apo E binds to receptor

B

B

B

B

B

B

B

B

B

B

B

VLDL interacts with LPL

Produce LDL

non-hepatic tissues

LIVER

LDL into cell delivers cholesterol

HDL scavenges cholesterol

Figure4. Endogenous pathway of lipid transport.


LDL receptor relative content of triacylglycerol, cholesterol and protein

Recycling of clathrin and receptor

Recycling of clathrin

Ligand/receptor dissociate in sorting endosome

transport vesicle- lysosome fuse forming late endosome

lysosome

clathrin-

coated pit

ooo

Golgi

late endosome

NPC-1 mediated transfer

ooo

free pool of

cholesterol

ACAT

CEcholesterol

B100  a. acids

endocytosis

CE stored in droplets

vesicle

CE

CE

LDL

CE

Figure 5. Steps in the cellular uptake of cholesterol via the LDL receptor.


Table 3. Summary of lipoprotein functions relative content of triacylglycerol, cholesterol and protein


Table 4. Summary of apoproteins and their characteristics relative content of triacylglycerol, cholesterol and protein