Syllabus Revisions

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Syllabus Revisions

• No Quiz March 7
• Paper summary- 10 pt
• 2 quizzes 10 pt each
• Abstract (include at least 2 references) 20 pt
• Midterm moved to March 3 (Monday)
• Dr. Allred move to March 5
• Dr. Martha Belury to March 10 (not 12)

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Website

• http//class.fst.ohio-state.edu/fst761/761home.htm
  l
• Lectures
• Some papers
• Syllabus

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Structure and Properties of Lipids

• Stipanuk Chapter 3!

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Lipids and Their Functions

• Barriers
• Receptors
• Antigens
• Sensors
• Electrical insulators
• Biological detergents
• Membrane anchors
• ENERGY

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Plasma Membrane
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(No Transcript)
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Tay-Sachs Disease

• Lysosomes are acidified cytoplasmic organelles
• Contain degradative enzymes (orderly destruction
  of cellular componets)
• intralysosomal build up of GM2 gangliosides due
  to defect in hexosaminidase A

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Electrical Insulators
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Lorenzos Oil

• Adrenoleukodystrophy (ALD)
• Solubilization and removal of myelin sheath
• Build up of very long chain saturated fatty acids
  (24-26 carbons!)
• Poor b-oxidation in peroxisomes
• Feed unsaturated short fatty acids (Lorenzos
  oil) and compete with uptake
• Oil may help but does not cure

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Biological Detergents

• Bile salts aid in the emulsification of lipids in
  the small intestine.
• Bile is synthesized from cholesterol in the liver
• Stored in the gall bladder and release after a
  lipid-containing meal
• Emulsification allows lipases to digest
  triglyceride

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Energy

• Average western diet contains 100 to 150 grams of
  dietary fat
• Providing 900-1350 kcal or 40 of total caloric
  requirements / day
• 9 kcal/gram

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Why is fat a good energy source?

• More highly reduced than carbohydrates
• No water more energy / gram
• More energy and less weight
• 70 kg man (11 body fat)
• 100,000 kcal stored as fat
• 600 kcal as glycogen

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Lipid Structures
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Fatty Acids
Myristic 140
Linoleic 182w6 (18.2 9c12c)
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Naming Fatty Acids Fun and Easy

• w Formula system
• Number of carbon atoms starts from the methyl end
• Location of first double bond is indicated by
  single number (preceded by w)
• Double bonds occur every 3 carbons
• (182w6) 18 carbons, 2 DB, Start at C6 from
  methyl end
• - Delta system D 18.2 9c12c

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Linolenic Acid (183w3)
1 2 3 4 5 6
7 8 9 10 11-17
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Answer 1

• 20 carbons, 5 double bonds, First double bond at
  3 carbon from methyl end
• 205w3
• Omega 3 polyunsaturated fatty acid

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Answer 2
EPA or Eicosapentaenoic acid Omega 3 fatty acid,
fish oil Antiinflammatory Important for
neonates breastfed children have higher
IQs Supplemented in infant formulas benefit?
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Dietary linolenic/linoleic acid
(essential)
Dietary EPA
(-)
()
Arachidonic acid
Prostaglandins / Eicosanoids
Macrophage
Proinflammatory Cytokines (IL-1, TNF)
AA
After Babcock et al. Nutrition 161116-1118, 2000
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Answer 3
204w6
1
3
5
8
11
14
17
19
2
4
6
7
9
10
12
13
15
16
18
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Omega 6 double bond
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Glycerol and glycerophospholipids
Glycerol-3-phosphate
Glycerol
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Triacylglycerols (fats and oils)
Palmitic (c160)
Stearic (c180)
Oleic (181w9)
a-Palmito-b-stearo-aolein
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Sphingolipids
ceramide
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galactocerebroside
sphingomyelin
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Steroids
cholesterol
estradiol
testosterone
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Fat Soluble Vitamins and Coenzymes
Coenzyme Q
Vitamin E
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Digestion and Absorption of Lipids
Dietary Lipids
Triglycerides
Phospholipids
Cholesterol esters
digestion
Free fatty acids monoglycerides
Free fatty acids lysophospholipids
Cholesterol
absorption and restoration
Triglycerides
Phospholipids
Cholesterol esters
Free fatty acids
Cell membranes
Bile acids
Steroid hormones
Energy (muscle)
Energy storage
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Digestion and Absorption of Dietary
Lipids Triglycerides
Emulsification
Begins in the stomach gastric lipase (low
pH) 15-20 FA are cleaved Upper small
intestine pancreatic lipase Formation of mixed
micelles Absorbed by enterocytes
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Gastric Lipase

• Optimal pH is 4. Still active in small intestine
• Cleaves fatty acids at the sn-3 position
• 1,2 Diglycerides and FA help in emulsification

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Emulsification
Bile salts
physical disruption
lipid
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Lipase Activity
Bile salts/phospholipids/fatty acids
Pancreatic Triglyceride lipase (PTL)
Triglycerides cholesterol
Emulsified particle
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Enzymatic Action of Pancreatic Lipase
PTL
PTL
H20 H20
2-monoglyceride
2 FFA
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Colipase

• Heat stable protein required for lipase activity
• Secreted as procolipase
• Trypsin activates
• In vivo data are limited

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Colipase knockouts

• Clps -/- appear normal at birth
• 60 die within the first 2 weeks of life
• Fat malabsorption on high fat diets
• Reduced body weight / After weaningnormal
• Conclusion
• Role in postnatal development
• -Regulation of body weight set point

DAgostino D., et al. J Biol Chem 27771707177,
2002
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(No Transcript)
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(No Transcript)
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Olestra Side Effects

• Fecal urgency
• Lower absorption of vitamin E and carotenoids

Warning Label
This product contains Olestra. Olestra may
cause abdominal cramping loose stools. Olestra
inhibits the absorptionof some vitamins and
other nutrients. Vitamins A,D, E and K have been
added.
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Xenical (Orlistat)
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• 120 mg three times / day
• 1 yr period

A. Ballinger, SR Perkins/European Journal of
Pharmacology 440 (2002) 109-117
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brush border
FFA Monoglyceride
Mixed Micelle
Free fatty acids
Free Fatty acids
enterocyte
Lumen of small intestine
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micelle
FA
FA
PL
Triglyceride
micelle
monoglyceride
MG
FA
Phospholipid
micelle
lysoPL
lysoPL
Cholesterol ester
Cholesterol ester
Free cholesterol
SCFA
Short chain FA
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activated
Fatty Acyl CoA
FA
Triglyceride
Diglyceride
MG
Chylomicron
Phospholipid
lysoPL
Cholesterol
Cholesterol ester
How do FA get from brush border to ER where TG
synthesis occurs?
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FABP
TG
Chylomicron
Free fatty acids
ER
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Resynthesis of Trigylcerides in Enterocytes
SH
Fatty acid
High Energy Thioester bond
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(No Transcript)
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Monacylglycerol acyltransferase
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Diacylglycerol Acyl transferase
triglyceride
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Chylomicrons
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Readings

• Pay attention to methods and results
• Look at the figures along with results
• Bring questions
• Paper summary
• Summarize hypothesis, methods, results and
  conclusions (2 pages double spaced?)
• In your own words
• Dont worry about last figure in 1st paper