1. Section VI. Lipid Metabolism
Section VI. Lipid metabolism overview:
Major categories of lipids (not very water-soluble):
Fatty acids and triagylclycerol (TG)
Glycerophospholipids and sphingolipids
Eicosanoids (prostaglandins, thromboxanes)
Cholesterol, bile salts, steroid hormones
Fat-soluble vitamins (A, D, E, K)
Triacylglycerol

2. Overview Fatty acid metabolism
Fatty acid metabolism: (Chapts. 32, 33)
Fatty acids can be dietary or synthesized in liver
Can be oxidized for energy → CO2 and H2O
Can be stored as triacylglycerol in adipose tissue
Can be used to make phospholipids and sphingolipids for membrane components

3. Overview of cholesterol metabolism
Cholesterol metabolism (chapt. 34):
Is incorporated into membranes for stability
Is a precursor for bile salts (gall bladder secretes)
Is a precursor for steroid hormones

4. Overview lipoprotein particles in blood
Lipoprotein particles transport lipids in blood:
Triacylglycerol is major dietary lipid:
Digested in intestinal lumen: free FA and 2-mono- acylglycerol are reconverted to TG in intestinal cells
TG are packaged as chylomicrons (apoB) and secreted into blood ; matured with additional proteins
VLDL (very-low-density-lipoproteins) produced in liver from dietary carbohydrates (insulin stimulated)
Lipoprotein lipase (LPL) on cells degrades the lipoproteins; FA into cells
HDL (high-density-lipoproteins) transport excess cholesterol to liver; exchange proteins

5. Lipid metabolism overview
Triacylglycerol metabolism:
Fed state:
TG digested to 2-MG and FA, into intestinal cells
TG reform (chylomicrons) with protein, into blood
Liver forms VLDL by lipogenesis from sugars
VLDL donates protein to chylomicron, which binds LPL on cells and is cleaved to release FA into muscle, adipose
Fasting state:
Fatty acids, glycerol released from adipose
Glycerol used for gluconeogenesis liver
FA used for ketone bodies, or oxidation (muscles, other)

6. Ch. 32 Digestion and Transport of Dietary Lipids
Chapt. 32
Ch. 32 Digestion and Transport
of Dietary Lipids
Student Learning Outcomes:
Explain digestion of triacylglycerols (TG) to free fatty acids (FA) and 2-monoacylglycerol (2-MG)
Describe the role of bile salts in this process
Describe how micelles enter epithelial cells, and are reconverted to TG
Explain how TG plus apoproteins and other lipids form nascent chylomicrons that exit cells
Describe role of HDL lipoproteins to mature the nascent chylomicrons, and breakdown of particles

7. I. Digestion of dietary triacylglycerols
Major fat in diet (storage of lipids plants, animals)
Lipases digest to 2-monoacylglycerol (2-MG)
Bile salts emulsify fat in small intestine
Bile salts derived from cholesterol
Fig. 1 fatty acids in triacylglycerol
Fig. 2, a bile salt

8. Digestion of dietary triacylglycerols: Lipases digest
Digestion, absorption
Digestion of dietary triacylglycerols:
Lipases digest
Bile salts emulsify, colipases aid lipases
TG reform in epithelium
Fig. 3:TG, triacylglycerol;
BS, bile salt, FA, fatty acid
2-MG, 2-monoacylglycerol

9. Enzymes degrade lipids
Lipases cleave C1, C3 of TG
Cholesterol esterase removes FA
Phospholipase degrades phospholipid
Figs. 5,6

10. Absorption into intestinal epithelial cells:
FA, 2-MG, cholesterol, other lipids, BS in micelles
Lipids absorbed through microvilli, not bile salts
Bile salts are recycled
Short, med-chain FA absorb directly epithelium, enter bloodstream bound to serum albumin
Figs. 3,6

11. TG are resynthesized in intestinal epithelia
III. Chylomicrons
III. Chylomicrons
TG are resynthesized in intestinal epithelia
ATP activates FA → FA-CoA (in Smooth ER)
Apoproteins and other lipids bind
[synthesis of TG in liver, adipose starts with phosphatidic acid]
Fig. 7

12. Blood lipoprotein particles transport lipids:
Blood lipoproteins
Blood lipoprotein particles transport lipids:
Chylomicrons – produced in intestinal cells from dietary fat; carry TG in blood
VLDL – produced from liver mainly from dietary carbohydrate; carries TG in blood
IDL - produced in blood (remnant of VLDL)
LDL – produced in blood (remnant of IDL after TG digestion; high concentration of cholesterol;
endocytosed by liver, other tissues (LDL receptor)
HDL – produced in liver, intestine; exchanges proteins and lipids with other lipoproteins; returns cholesterol to liver

13. Transport of lipids in blood
Transport of lipids uses lipoprotein complexes:
Lipids are not soluble in water; would coalesce
Phospholipids, protein on outside; hydrophobic inside
Cholesterol esters have fatty acid moiety
Ex. VLDL from liver (very-low density lipoprotein)
Fig. 8
Fig

14. Nascent chylomicrons from dietary TG: SER enzymes reform the TG
Least dense lipoproteins (lot of TG)
Proteins made on RER
Apoprotein B-48
Figs. 9,10

15. B-apoprotein gene encodes two polypeptides:
Apoprotein B gene
B-apoprotein gene encodes two polypeptides:
ApoB-100 in liver VLDL particles
ApoB-48 in intestinal cells is only 48% length
RNA editing changed codon in mRNA
Fig. 11

16. IV. Lipoprotein particles transport dietary lipids in blood
Additional proteins form mature chylomicrons:
‘Nascent chylomicrons’ exocytosed into blood
Acquire additional proteins from HDL particles
ApoCII binds enzyme LPL on cell surfaces
Lipoprotein lipases
ApoE binds receptor on liver
cell for recycling
Fig. 12

17. Chylomicrons from dietary lipids:
Fate of chylomicrons
Chylomicrons from dietary lipids:
matured in blood by HDL particle interaction
Are digested at capillary wall by LPL (CII activates)
Insulin stimulates more LPL on surface
FA binds albumin in blood
FA into muscle (energy)
FA into adipose (store)
Remnants bind liver
through ApoE-receptor
Recycled in lysosome
Fig. 13

18. Olestra is artificial fat substitute Tastes like fat, not metabolized
sucrose with fatty acyl groups esterified on OH
resistant to hydrolysis by lipases, passes through
carries lipid-soluble vitamins

19. Triacylglycerols are major fat source in diet
Key concepts:
Key concepts:
Triacylglycerols are major fat source in diet
Lipases perform digestion, bile salts emulsify
Free fatty acids and 2-monoacylglycerol form
Micelles transport components into intestinal cells
Nascent chylomicrons are reformed from TG, cholesterol and apoB-48 protein; pass into blood
HDL particles contribute additional proteins to form mature chlymicrons
LPL (lipoprotein lipase) on cell surface cleaves TG and cells gain FA; remnants recycled in liver

20. An absence of chylomicrons after eating
Review question
Type III hyperlipidemia is caused by a deficiency of apoprotein E. Analysis of the serum of patients with this disorder would exhibit which of the following?
An absence of chylomicrons after eating
Above-normal levels of VLDL after eating
Normal triglyceride levels
Elevated triglyceride levels
Below-normal triglyceride levels