Download Document

LIPID
METABOLISM
December 2007
5/3/2017 4:11 PM
1
Monogastric Digestion
Challenges
1.Lipids are not water soluble
2.Triglycerides too large to be absorbed
Digestive solution
1.Triglycerides mix with bile and pancreatic secretions
2.Emulsification and digestion
Bile
 Produced in liver, stored in gallbladder
 Except horse
 Alkaline solution composed of:
 Bile salts
 Cholesterol
 Lecithin
 Bilirubin
 Responsible for fat emulsification
 Detergent action
Mixed micelle formed by bile salts, triacylglycerols and pancreatic lipase.
Digestion of Lipid
 Bile salts emulsify lipids
 Pancreatic lipase acts on triglycerides
 Triglycerides
sn-2
monoglyceride + 2 fatty acids
 Pancreatic colipase
 Activated by trypsin
 Interacts with triglyceride and pancreatic lipase
 Displaces bile to allow recycling
 Improves activity of pancreatic lipase
Pancreatic Colipase
Secreted from pancreas as 
procolipase
Activated (cleaved) by trypsin

Anchors lipase to the micelle 
One colipase to one lipase
(i.e., 1:1 ratio)

Emulsification
 Produces small lipid spheres
 Greater surface area
 Lipases attack TG at 1 and 3 positions
G Fatty Acid1
l
y
c
e Fatty Acid2
r
o
l Fatty Acid3
Triglyceride
Lipase
2 H20
G
l
y
c Fatty Acid2
e
r
o
l
2-Monoglyceride
+
Fatty Acid1
Fatty Acid3
2 Free Fatty Acids
Digestion of Lipid
 Phospholipase A1 and A2
 Hydrolyzes fatty acids from phospholipids
 Cholesterol esterase
 Hydrolyzes fatty acids from cholesterol esters
Micelle Formation
 Complex of lipid materials soluble in water
 Contains bile salts, phospholipids & cholesterol
 Combines with 2-monoglycerides, free fatty acids
and fat-soluble vitamins to form mixed micelles
Micelle Formation
Lipid Absorption
simple diffusion
exocytosis
Short and
medium
chain fatty
acids
Overview of Fatty Acid Uptake
 Short- and medium-chain fatty acids
 Enter portal blood directly from enterocytes
 Bound to albumin in blood
 Albumin–FFA complex
 Oxidized in liver or elongated and used for triglyceride
formation
 Long-chain fatty acids
 Form chylomicrons
 Drain into the lymphatics via the lacteal in mammals (no
lacteal in avian small intestinal villi)
 Enter bloodstream at the thoracic duct


Upstream from liver
Slow entry into the blood
Overview of
Lipid
Digestion in
Mammals
Fatty Acids
β-Oxidation
5/3/2017 4:11 PM
15
Fatty Acids Beta Oxidation
5/3/2017 4:11 PM
16
5/3/2017 4:11 PM
17
Fatty Acid Translocation into Mitochondrion
5/3/2017 4:11 PM
18
Stages of Fatty Acids Beta Oxidation
5/3/2017 4:11 PM
19
5/3/2017 4:11 PM
20
5/3/2017 4:11 PM
21
5/3/2017 4:11 PM
22
5/3/2017 4:11 PM
23
5/3/2017 4:11 PM
24
5/3/2017 4:11 PM
25
 β - Oxidation Fatty Acids (with odd carbon number)
 β - Oxidation Fatty Acids (Peroxisomes)
 α - Oxidation Fatty Acids
 ω - Oxidation Fatty Acids
5/3/2017 4:11 PM
26
Odd Chain Fatty Acids
Beta Oxidation
5/3/2017 4:11 PM
27
5/3/2017 4:11 PM
28
Unsaturated Fatty Acids
Beta Oxidation
5/3/2017 4:11 PM
29
Biohydrogenation of Linoleic Acid
Linoleic acid (18:2)
isomerase
cis-9, trans-11 CLA
reductase
trans-11 18:1
reductase
Stearic acid (18:0)
Intermediate fatty acids are conjugated linoleic acids
Regulation of Beta
Oxidation
5/3/2017 4:11 PM
31
5/3/2017 4:11 PM
32
 Carnitine Deficiency
 CPT-I and CPT-II Deficiency
 Sulfonylurea Drug Consumption
 Jamacaican Vomitting Sickness
 Dicarboxylic Aciduria
 Refsum's Disease
 Zellweger‘s Disease
5/3/2017 4:11 PM
33
Ketogenesis
(Synthesis of Ketone Bodies)
5/3/2017 4:11 PM
34
5/3/2017 4:11 PM
35
5/3/2017 4:11 PM
36
5/3/2017 4:11 PM
37
5/3/2017 4:11 PM
38
Regulation of
Ketogenesis
5/3/2017 4:11 PM
39
5/3/2017 4:11 PM
40
CLINICAL ASPECTS
 Impaired Oxidation of Fatty Acids
Gives Rise to Diseases Often
Associated With Hypoglycemia
5/3/2017 4:11 PM
41
Fatty Acid Synthesis
(Lipogenesis)
5/3/2017 4:11 PM
42
Fatty acid synthase complex
5/3/2017 4:11 PM
43
Methyl malonyl-CoA Biosynthesis
5/3/2017 4:11 PM
44
Fatty acid synthesis: stage-1
5/3/2017 4:11 PM
45
Fatty acid synthesis: stage-2
5/3/2017 4:11 PM
46
Fatty acid synthesis: stage-3
5/3/2017 4:11 PM
47
Fatty acid synthesis: stage-4
5/3/2017 4:11 PM
48
Fatty acid synthesis: stage-5
5/3/2017 4:11 PM
49
5/3/2017 4:11 PM
50
FA Elongation System
 ER ( microzomes) is the local of EFA
 Elangase Enzyme System
5/3/2017 4:11 PM
51
Acety CoA transportion
and NADPH production
Pathways
5/3/2017 4:11 PM
52
5/3/2017 4:11 PM
53
Regulation of Lipogenesis
 Nutritional State
 Carbohydrate or Lipid Intake
 Regulation of Acetyl-CoA Carboxylase
 Regulation of Pyruvate Dehydrogenase
 Effect of Hormone
5/3/2017 4:11 PM
54
Unsaturated fatty acid Biosynthesis
 One unsaturated FA;
 Liver is the position synthesis
 The first local is the position Δ9
 Δ9 Desaturase enzyme system in ER ( O2 + NADPH+ Cytochrome b5)
 Poly unsaturated FA;
5/3/2017 4:11 PM
55
5/3/2017 4:11 PM
56
5/3/2017 4:11 PM
57