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ACC regulation
Covalent
Allosteric
Transcriptional
FAS pathway
Dietary/Hormonal
Learn chemical reactions
Stipanuk 351-364
Overview
Transport dietary lipids from intestine to liver (exogenous)
Transport lipids from liver to peripheral tissues
(endogenous)
Lipoproteins
Core of TG and CE
Surface of phospholipids and some cholesterol
Apolipoproteins (regulators of LP metabolism)
CM, VLDL, IDL, LDL, HDL
Chylomicron Assembly
-assembled in enterocyte golgi/ER
-Apolipoprotein (Apo) B organizes assembly
-B48
- Requires phospholipids
-2 forms of apo B
-B100, large- liver
-B48, smaller intestine
- Picks up apo A,C and E in plasma
- TG composition closely resembles dietary intake
Abetalipoproteinemia
Rare genetic disease
No apo-B containing lipoproteins in
plasma
Cholesterol is ~25% of normal
Mutation in MTP
Liver
Dietary TG
CE
Apo B48
cholesterol
FFA
FFA-FABP
Apo B48
TG
micelle
CII
TG/CE
A
CIII
chylomicron
ER/golgi
enterocyte
Plasma
Type
Association
Function
B48
Chylomicron
B100
VLDL,IDL,LDL
C-II
Activates LPL
C-III
Inhibits LPL
A-1
HDL/Chylomicron
LCAT activator
(lecithin:cholesterol
acyltransferase)
Plasma
FFA
B48
CIII
CII
TG
Oxidation
muscle
Lipoprotein
Lipase
TG/CE
chylomicron
FFA
Lipoprotein
Lipase
B48
CIII
CII
TG/CE
E
FFA
Chylomicron remnant
G3P
Triglyceride
storage
adipose
liver
B48
insulin
CII
LPL
CIII
TG/CE
chylomicron
FFA
glut4
Glucose
(+)
CoA
G3P
Fatty acyl CoA
adipose
Triglycerides
Insulin
regulated
glucose
transport
B48
insulin
CII
LPL
CIII
TG/CE
chylomicron
FFA-albumin (oxidation)
Glucose
FFA
(-)
glut4
CoA
G3P
Fatty acyl CoA
adipose
Triglycerides
Insulin
regulated
glucose
transport
Ob mice
Fasted/ exercise
state
Lactating Mammary
gland
LPL activity
Plasma
Dietary Carbohydrate
glucose
B48
LDL receptor
TG/CE
LIVER
pyruvate
Acetyl CoA
Acetyl CoA
mitochondria
E
TG
CMr
cholesterol
(exogenous)
FFA
FFA
B100
TG
CE/TG
Cholesterol
(endogenous)
VLDL
VLDL
Plasma
Dietary Carbohydrate
glucose
LIVER
pyruvate
Acetyl CoA
Acetyl CoA
mitochondria
cholesterol
(exogenous)
TG
B100
FFA
FFA
TG
CE/TG
Cholesterol
(endogenous)
VLDL
VLDL
Cholesterol.
In bile
From liver
LIVER
Endogenous cholesterol
B100 E
CE/TG
CII
VLDL
B100 E
LDL receptor
CE/TG
IDL
LPL
FA
B100
CE
LDL
FFA
muscle
adipose
Extrahepatic tissue
LDL receptor
Michael S. Brown
Joseph Goldstein
Regulated by SREBP
monitors free cholesterol
Free cholesterol =
HDL Formation
Steroidogenic
cells
2. Cholesterol
for steroid
synthesis
Liver
Cholesterol
to other
lipoproteins
3. Cholesterol-ester
transfer protein
(CETP)
1. Cholesterol
to liver
HDL
A
ApoA
Lecithin-cholesterol acyl
transferase (LCAT)
A
Pre--HDL
Discoidal/lipid poor
Cholesterol from
Liver and intestinal
Cells via ABCA1
A
Pre--HDL
Unesterified cholesterol-rich
VLDL
CE
FFA
CETP
LPL
Liver
(LDL receptor)
TG
IDL
TG
HDL
CETP
CE
LPL
TG
FFA
CETP
Liver
(LDL receptor)
CE
LDL
Extrahepatic tissues
Liver
Cholesterol esters
Cholesterol is reused
or excreted in bile
hydrolysis
Direct
Free cholesterol
ABCA1
A
Pre--HDL
LCAT
HDL
CETP
Cholesterol to
VLDL, IDL,LDL
1. LCAT deficiency?
2. CETP deficiency?
3. apo AI deficiency?
Chylomicron
VLDL
High CARB
Insulin
(+)
FA/TG
(+)
Acetyl CoA
Dietary Fat
Intestinal Epithelium
(+)
Glucose
LDL
Liver
Dietary fat
Bile salts
small
intestine
Endogenous
cholesterol
extrahepatic
tissue
Exogenous
cholesterol
HDL
chylomicrons
chylomicrons
reminants
VLDL
IDL
capillaries
Lipoprotein Lipase
Lipoprotein Lipase
FFA
Adipose, muscle
FFA
Atherogenic Particles
MEASUREMENTS:
VLDL
VLDLR
Apolipoprotein B
Non-HDL-C
IDL
TG-rich lipoproteins
Thanks to Lipids Online: http://www.lipidsonline.org/
LDL
Small,
dense
LDL
Cholesterol to liver
LDL
vascular endothelium
(+)
differentiate
Oxidized LDL
Macrophage
LDL (+)
(-) HDL
Arterial intima
Next Week
Feb 23 Dr. Neile Edens Ross Labs
Feb 25 Beta oxidation/Cholesterol
Feb 27 Exam Review/Rough Draft
revisions