Download Section VI. Lipid metabolism overview:

Section VI. Lipid Metabolism
Overview Fatty acid metabolism
Section VI. Lipid metabolism overview:
Fatty acid metabolism: (Chapts. 32, 33)
Major categories of lipids (not very water-soluble):
• Fatty acids can be dietary or synthesized in liver
• Fatty acids and triagylclycerol (TG)
• Can be oxidized for energy → CO2 and H2O
• Glycerophospholipids and sphingolipids
• Eicosanoids (prostaglandins, thromboxanes)
• Cholesterol, bile salts, steroid hormones
• Can be stored as triacylglycerol in adipose tissue
• Can be used to make phospholipids and
sphingolipids for membrane components
• Fat-soluble vitamins (A, D, E, K)
Triacylglycerol
Overview of cholesterol metabolism
Overview lipoprotein particles in blood
Cholesterol metabolism (chapt. 34):
Lipoprotein particles transport lipids in blood:
• Is incorporated into membranes for stability
Triacylglycerol is major dietary lipid:
• Digested in intestinal lumen: free FA and 2-monoacylglycerol 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
• Is a precursor for bile salts (gall bladder secretes)
• Is a precursor for steroid hormones
1
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)
I. Digestion of dietary triacylglycerols
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
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
Digestion, absorption
Digestion of dietary
triacylglycerols:
• Lipases digest
• Bile salts emulsify,
colipases aid lipases
• TG reform in epithelium
Fig. 1 fatty acids in triacylglycerol
Fig. 2, a bile salt
Fig. 3:TG, triacylglycerol;
BS, bile salt, FA, fatty acid
2-MG, 2-monoacylglycerol
2
Enzymes degrade lipids
Absorption
Enzymes degrade lipids:
• Lipases cleave C1, C3 of TG
• Cholesterol esterase removes FA
• Phospholipase degrades phospholipid
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. 5,6
Figs. 3,6
III. Chylomicrons
Blood lipoproteins
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
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
3
Transport of lipids in blood
Nascent Chylomicrons
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. 33.10
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
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
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
4
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
Olestra
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
Fig. 13
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
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?
a.
b.
c.
d.
e.
An absence of chylomicrons after eating
Above-normal levels of VLDL after eating
Normal triglyceride levels
Elevated triglyceride levels
Below-normal triglyceride levels
5