दोषेण तीव्रो विषयः कृष्ण सर्प विषादवर्
विषं विहन्ति भोक्तारं द्रष्टारं चक्षुषाप्ययं
దోషేణ తీవ్రో విషయః కృష ణ సర్ప వి
షాదపి
ని ి భోkrishna
క్తిర్ంsarpa
విషంteevro
నిహvishayah
వ్రదష్టషా
ర ర్ం
Doshaena
vishaadapi
visham nihanti bhoktaaram
drashtaaram
చక్షుషాప్య
యంchakshushaapyayam
The sensual pleasures are even more virulent and poisonous in their evil
effects than the deadly poison of a King Cobra. The poison can kill only if
it is absorbed but the very sight of these is enough for destruction.
website: www.drsarma.in
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
What are the important
components (two) of
lipids in the plasma ?
1. Ester. Cholesterol (EC)
2. Triglycerides (TG)

What are the other two
components in lipids in
their outer layer ?
1. Free Cholesterol (FC)
2. Phospholipids (PL)
What are Apoproteins ?
 Why are they needed in
the lipid molecules ?

1. The outer protein coat is
made of Apoproteins
2. To make lipids soluble and
thus help transport
Lipids or Fats
(Hydrophobic)
Size < RBC
TG, EC
Phospholipids
Free Cholesterol
(Hydrophilic)
Apolipoproteins
A, B, C, E, (a)
(Amphiphatic)
• Free fatty acids (FFA) to Triglyceride (TG)
– Source of energy to the tissues
– Stored as TG; Metabolized to CO2 and H2O
– Exogenous (diet) and De novo synthesis
• Free Cholesterol (FC) to Esterified (EC)
–
–
–
–
–
Cell membrane integrity
Bile acids synthesis
Steroid hormones synthesis; Vitamin D in skin
Can not be broken down
Exogenous (diet) and De novo synthesis
TG
EC
Apoprotein boat
1.
2.
3.
4.
Make the lipids soluble and transportable
Structural Integrity of the lipoprotein
Act as ligands for cell receptors
Activate enzymes such as LPL, LCAT as cofactors
Measurements
Chylo M
VLDL VLDLR
TG-rich lipoproteins
Apolipoprotein B
Non-HDL-C
IDL
LDL Lp(a) SLDL
The smaller the particle
The greater is the danger
Chylomicrons
VLDL
IDL
<< 1.006
< 1.006
< 1.019
LDL
Small LDL
HDL
< 1.063
< 1.085
< 1.210
Atherogenicity increases as density increases
A-I
A-I
CE
TG
A-II
A-I, A-II = Apo lipoprotein A-I, A-II;
CE = cholesterol ester; TG = triglycerides
A-I
CE
A-I
CE
CE
A-II
HDL 1
HDL 2
APO A I Protective
A-II
HDL 3
Alcohol increases
Synthesized
Generated
•HDL
•VLDL
•Lp(a)
•Chylomicrons
•LDL
•IDL (VLDL R)
•Chylomicron R
Through
lymphatic
system to
the liver
Intestinal
epithelial cell
Biliary
cholesterol
MTP
CM
Cholesteryl esters
ACAT
(esterification)
Free
cholesterol
excretion
ABCG5
ABCG8
Dietary
cholesterol
Luminal
cholesterol
Bile
acid
Micellar
cholesterol
uptake
Bays H et al. Expert Opin Pharmacother 2003;4:779-790.
Lymph
Enterocyte
Intestinal
Lumen
Ezetimibe
Free Cholesterol
NPC1L1
ACAT
Avasimibe
Cholesterol
Ester ABCG5/G8
14
Pancreatic Esterase
Lymph
Enterocyte
Intestinal
Lumen
2 Fatty Acids
+
Mono glyceride
Chylomicrons
DGAT
APO B48
Triglyceride
16
Intestinal Lipase
MF in Vascular
Endothelium
Free Cholesterol
LIVER
EC
UEC
HDL
L CAT
Enzyme
Bile
A-I
F
C
CE
LCAT
SR-BI
Liver
A-I
CE
FC
CE
FC ABC1
Nascent
Macrophage
HDL
Mature HDL
ABC1 = ATP-binding cassette protein 1; A-I = apolipoprotein A-I;
CE = cholesteryl ester; FC = free cholesterol;
LCAT = lecithin:cholesterol acyltransferase;
SR-BI = scavenger receptor class BI
Bile
Nascent HDL
A-I
Mature HDL
FC
CE
SR-BI
Liver
LDLR
A-I
CE
Macrophage
FC
CE
LCAT
FC
CETP
CE
X
ABC1
SRA
B
VLDL/LDL
Torcitrapib
CETP = cholesteryl ester transfer protein
LDL = low-density lipoprotein
LDLR = low-density lipoprotein receptor
VLDL = very-low-density lipoprotein
Apoprotein Primary Source Association
Function
Apo A-I
Intestine, Liver
HDL, Chylomicron
ABCA1, LCAT
Apo A-II
Liver
HDL, Chylomicron
LCAT, Strut. Pro
Apo A-V
Liver
VLDL, IDL, Chylomicr
LPL activity
Apo B 48
Intestine
Chylomicrons
St. Pr. Chylo M
Apo B 100
Liver
LDL, IDL, VLDL, Lp (a) Structural Prot.
Apo (a)
Liver
Lp (a) - plasminogen
Unknown
Apo C-II
Liver
Chylo, VLDL, HDL
LPL Cofactor
Apo C-III
Liver
Chylo, VLDL, HDL
Inhibits binding
Apo E
Liver
CMR, IDL, HDL
Ligand LDL-R
Receptor
Primary Site
Binds / Transports
Function
LDL-R
Liver, Tissues
LDL, CMR, IDL
Trap, Excretion
LRP
Liver, Tissues
Apo E – CMR, VLDLR
Trap, Excretion
SR-B1
Liver, M Phages Apo AI – binds HDL
Reverse Ch. Tr.
ABCA1
Transporter
Cholesterol to HDL
Clears MP Chol.
ABCG1
Transporter
Cholesterol to HDL
Clears MP Chol.
ABCA5/8
Intestine, Liver
Efflux of Cholesterol
Excre. Stanols
NPC1L1
Intestine
Cholesterol/Stanols
Lumen to Cells
• Lipoprotein Lipase : LPL
– Capillary endothelium – muscle, heart,
adipose tissue, TG hydrolysis to FFA & Glycerol
– Converts CM and VLDL to their remnants
– Apo CII is the cofactor, Insulin stimulates LPL
• Hepatic Lipase : HL
–
–
–
–
Present in hepatic sinusoids
Hydrolysis of TG to FFA and glycerol
IDL – converted to LDL
HDL – converted to small lipid poor HDL
• Endothelial Lipase : EL
– Member of LPL family
– Made by endothelial cells
– Hydrolyses the phospholipid in HDL
• Lecithin Cholesterol Acyl Transferase : LCAT
– Produced in the liver
– In the plasma catalyzes FC to EC in HDL
• Cholesterol Ester Transfer Protein : CETP
– Plasma protein bound to HDL, from the liver
– Transfers EC to CM, VLDL, IDL, LDL from HDL
– Transfers TG from CM, VLDL, IDL , LDL to HDL