Section VI. Lipid Metabolism Section VI. Lipid metabolism overview: Major categories of lipids (not very water-soluble): Fatty acids and triagylclycerol.

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

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

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

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

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)

Chapt. 32

Ch. 32 Digestion and Transport of Dietary LipidsStudent 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

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

Fig. 1 fatty acids in triacylglycerolFig. 2, a bile salt

Digestion, absorption

Fig. 3:TG, triacylglycerol;BS, bile salt, FA, fatty acid2-MG, 2-monoacylglycerol

Digestion of dietary triacylglycerols:

• Lipases digest

• Bile salts emulsify, colipases aid lipases

• TG reform in epithelium

Enzymes degrade lipids

Enzymes degrade lipids:• Lipases cleave C1, C3 of TG• Cholesterol esterase removes FA• Phospholipase degrades phospholipid

Figs. 5,6

Absorption

Figs. 3,6

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

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

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

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. 8Fig. 33.10

Nascent Chylomicrons

Figs. 9,10

Nascent chylomicrons from dietary TG:• SER enzymes reform the TG• Least dense lipoproteins (lot of TG)• Proteins made on RER• Apoprotein B-48

Fig. 11

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

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

Fate of chylomicrons

Fig. 13

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-receptorRecycled 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

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.An absence of chylomicrons after eating

b.Above-normal levels of VLDL after eating

c.Normal triglyceride levels

d.Elevated triglyceride levels

e.Below-normal triglyceride levels