Llipid Metabolism Lecture For 2nd Year MBBS by DR Sadia Haroon
Llipid Metabolism Lecture For 2nd Year MBBS by DR Sadia Haroon
Llipid Metabolism Lecture For 2nd Year MBBS by DR Sadia Haroon
Tsao
Lecture 31 – March 29, 2006
LIPIDS:
BIOCHEMISTRY OF LIPIDOSES
AND ATHEROSCLEROSIS
Clinical Defect in Clinical Defects in
(Normal digestion)
Lipid Digestion Lipid Absorption
Short/medium
chain FFA
LDL receptor Wolman’s disease
LDL NPC disease
synthesis
receptor Tangier
(hypolipidemia)
lysosome/ NPC-1 FHC (type II)
Golgi
late endosome mediated
transfer free pool of
ACEH
CE cholesterol
cholesterol ACAT
endocytosis
CE stored
Cholesterol
Cholesterol release in droplets
Esterase
for transport to liver CE CE
LDL CERP induced
CE by cholesterol Cholesterol
metabolism to bile
acids or steroids
Membrane
Apo A1 receptor
Cholesterol
C
A
L
20 80
stone
normal
0 100
100 80 60 40 20 0
Table 1. Human gallbladder bile
% Bile Salt
composition
Bile Lecithin Cholesterol
Salt
Normal 80% 15% 5%
Gallstone 68% 22% 10%
(typical)
Low bile salts lower ability to dissolve cholesterol gallstones
VLDL cholesterol Dietary
Cholesterol synthesis via liver synthesis Cholesterol
Acetyl CoA via Circulation
LDL cholesterol
HMG-CoA A
HMG-CoA X Uptake via LDL receptor
reductase Mevalonate Intracellular Fates: esterification by
ACAT and storage;
Cellular Cholesterol
steroid hormone/ vitamin D synthesis
Esterification/removal by LCAT/HDL
N
T
E
E
S
I
X X XX
CE CE
CEC C
EC
E CEEC E CE
CE C
C E C E C E C E
CE CEE C EC E C E CECE
C EC E
CE
Chylomicrons are not CECE
ApoB48 helps processed by non-hepatic
with chylomicron tissues and therefore
assembly accumulate in the blood.
8 8 88 8 8 8
A1 Mature
B4B4BB44B4B4 B4
Remnant A1
A1
A1
A1 HDL
A1
A1 CII
CII
E E EE E E E
CII
CII
CII
E EEEEEE
CII
CII
X
X
E
E Receptor
Receptor
Lack of liver clearance of cholesterol in
type III hyperlipidemia
Diabetes:
cannot shutdown hormone sensitive lipase mobilize FFA
FFA liver TAGs VLDL circulation
VLDL pathologically excessive LDL
Oxidation of LDL
Pathogenesis
Oxidized LDL
1. Uptake by "scavenger receptors" on
macrophages that invade artery walls;
become foam cells
2. Elicits CE deposition in artery walls
3. Atherosclerosis/CAD can develop
TXA3
PGI2/ PGI3
HEALTHY
PGI3
Dietary 3 fatty acid favors platelet
intervention (cold water fish) disaggregation
PGI3 activity >> TXA3
HEALTHY
PGI2
Reendothelialization
Injury
PGI2
TXA2
Injury
Aggregated
Platelets
Blood Vessel Wall Endothelial Cell
Platelet Figure 9. Control of platelet aggregation:
Smooth
Factors leading to platelet aggregation
Muscle Cell
in atherosclerotic plaques
TXA2
Athero-
DAMAGED
sclerosis
PGI2
TXA2
CE laden
macrophages
("foam cells") Aggregated
Platelets
PGI2/3 & sat fat) and drug therapy (low dose aspirin,
antiox vitamins, chol lowering drugs)
Macrophage invasion
Athero-
DAMAGED
sclerosis
PGI2
TXA2
CE laden
macrophages
("foam cells") Aggregated
Platelets