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6. Looking forward to connect all & have a fruitful interaction
3. FLOW OF THE MODULES
Module
PDF (Post
Module)
Bites (Short
Videos)
Quizizz
Time: 8.30 to 10.15am
4. OBJECTIVES
ā¢ To Understand Lipids & their Role in Body
ā¢ To Understand & recall Lipoprotein, Apolipoprotein Types & roles.
ā¢ To Understand & remember Lipid Metabolism pathways.
ā¢ To understand & reproduce Cholesterol synthesis in Liver
ā¢ To Understand LDL receptor Role in Recycling LDL
5. MEET OUR FRIENDā¦ā¦
JAYESH 5 Months old
JAYESH 10 Yr old ā
Love for Fast Food
JAYESH 30 Yr old ā
Love for Fast Food
Continued
<70
mg/dl
6. MEET OUR FRIENDā¦ā¦
Dr Hiren Cardio.. Explaining
Jayesh about Lipids
What kind of report is this
whats this Triglyceride,
LDL ā¦ I guess Dr Hiren can
help meā¦
7. 0
1
0
2
0
3
0
4
1815
1854
1964
1985
isolated and purified
sterol from gallstones.
And he named it as
ācholesterol.ā
MICHEL EUGENE
CHEVREUL Nobel Prize for
explaining the
cholesterol synthesis.
(HMG-CoA reductase)
DR. KONRAD
BLOCH
Nobel Prize for LDL
pathway discovery.
MICHAEL BROWN & JOSEPH
GOLDSTEIN
Atherosclerosis Defined
ATHEROSCLEROSIS
HISTORY
8. LIPID DEFINITION
ā¢ Lipids are a broad group of organic compounds which include fats,
waxes, sterols, fat-soluble vitamins (Vit A, D, E and K), Mono, Di-
glycerides, phospholipids, and others.
ā¢ Lipids may be broadly defined as hydrophobic or amphiphilic small
molecules.
10. LIPIDS
ā¢ Cholesterol ā Source ā Animal derived Foods & Liver Synthesis
Function - Vit D & hormones Synthesis.
ā¢ Triglycerides ā Source ā Meat, Plant oils & Liver Synthesis
Function ā Energy Production, Insulation, Stored in Adipose Tissue.
ā¢ Phospholipids ā Synthesized within body
Function ā Cell membrane Synthesis.
Body Synthesized Food Source
Cholesterol Cholesterol
Triglycerides Triglycerides
Phospholipids
11. LIPOPROTEIN
ā¢ Lipoproteins - made of lipids (Cholesterol & Triglycerides ) and proteins
circulating through bloodstream to cells throughout body.
ā¢ Lipid part : Core (Interior) of hydrophobic lipids (triglycerides and cholesterol
esters) surrounded by amphiphilic lipids (like phospholipids) .
ā¢ Protein part : Proteins which bind to lipids are known as Apolipoproteins.
Apolipoprotein
12. LIPOPROTEIN TYPES
ā¢ Chylomicrons (CM)
ā¢ Chylomicrons Remnant (CM Remnant),
ā¢ Very Low Density Lipoprotein (VLDL),
ā¢ Intermediate Density Lipoprotein (IDL),
ā¢ Low Density Lipoprotein (LDL),
ā¢ High Density Lipoprotein (HDL),
ā¢ Lipoprotein (a)
HDL
A-1, A-2. E
liver
15. LIPOPROTEIN(a) - Lp(a)
ā¢ Lipoprotein(a) or LP(a) is a type of LDL (ābad cholesterolā).
ā¢ A second protein called Apolipoprotein or apo(a) loops around it in segments
called kringles.
ā¢ Apolipoprotein makes the LDL particles stickier. As a result, LP(a) builds up in
blood vessels, increasing the risk of cardiovascular problems.
16. QUIZ 1
a. Which of the following are lipid
Ans:-
1. Cholesterol
2. Kringles
3. Esters
4. Free Fatty Acids
5. Triglycerides
6. Phospholipids
b. Which of the following originates
form Liver
Ans:-
1. CM
2. LDL
3. VLDL
4. HDL
17. LETS SUMMARIZE
ā¢ Cholesterol, Phospholipids, Triglycerides & Free Fatty acids ā Lipid commonly found in
Body.
ā¢ Lipids are essential for various functions viz, Hormone, cell membrane synthesis, energy
production, insulation.
ā¢ CM, CM remnant, VLDL, IDL, LDL, Lp(a) & HDL are different lipoproteins.
ā¢ CM originating from Intestine, VLDL originates from Liver, HDL originates form Liver.
ā¢ Lipoprotein(a) or Lp(a) is a type of LDL (Bad), Apolipoprotein makes Lp(a) particles
stickier.
ā¢ Apo C-II is activator for lipoprotein lipase (LPL).
ā¢ Apo C-III raises plasma triglycerides through inhibition of LPL.
33. QUIZ 2
a. Which of the following Enzymes are
involved in Cholesterol Synthesis
Ans:-
1. HMG CoA
2. HMG CoA reductase
3. ATP Citrate Lyase
4. TCA
b. Which enzyme is responsible for
degradation of LDL receptor (LDLR)
Ans:-
1. PCSK9
2. NPC1L1
3. CETP
4. LPL
34. LETS SUMMARIZE
ā¢ CM & CM remnant are involved in Exogenous pathway, VLDL, IDL, LDL are involved
Endogenous pathway, HDL involved in Reverse Cholesterol pathway.
ā¢ Niemann-Pick C1- like 1 protein (NPC1L1) is responsible to uptake of Cholesterol form
intestinal lumen into intestinal cells.
ā¢ Cholesterol is synthesized in liver ā HMG CoA reductase & ATP Citrate Lyase are important
enzymes involved in the process.
ā¢ LDLR ā LDL receptor on Liver cells is responsible for plasma LDL reuptake & ā plasma LDL
levels.
ā¢ PCSK9 synthesized in Liver binds to LDLR on the liver cell surface and degrades the LDLR
via lysosomal degradation.
ā¢ Excess LDL in plasma tends to build up in arterial wall ā leading to Plaque formation &
narrowing the artery.
Meet our Small little friend Jayesh 5 months old.. Kid has low levels of cholesterolā¦.
As time move on our friend Jayesh has grown up and as we all love to have fast food ā he also started enjoying it and his love of fast food didnāt stop and continued even upto his adulthood.
His friends used to call him a fat guy and even his started feeling uneasy when he would walk long.
With that concern he mind he had visited a free lipid profile check up at nearby clinic yesterday.
Today while having his fav burger at nearby food plaza he got his lipid profile reports on mobile ā¦ seeing it he was confused & tensed
He decided to visit dr the next day and fixed appointment with Dr Hiren Cardiologist who has been his family dr since long.. Seeing Jayeshā¦ concern Dr. decided to spend some time in evening post his OPD to make him understand about lipids and there role in body first.. Lets Listen from Dr Hiren about Lipid and how they are metabolized in body.
Amphipathic refers to a molecule or structure that has both hydrophilic (water-attracting) and hydrophobic (water-repelling) regions.
The amphiphilic nature of some lipids allows them to form structures such as vesicles, multilamellar/unilamellar liposomes, or membranes in an aqueous environment.
Analogy ā 1. Truck / bus carrying LDL & TG in it, 2. Two Chocolates In wrapper. 3. Oil Tanker carrying crude oil.
To be transported in watery blood, such molecules must be made water soluble by combining them with proteins produced by liver and intestine. The lipid and protein combination thus formed is called lipoproteins.
Esterification is a chemical reaction in which an ester is formed through the combination of an alcohol and an organic acid (carboxylic acid). This reaction involves the removal of water (dehydration synthesis) and results in the formation of an ester linkage. The general reaction equation for esterification is:
CarboxylicĀ acid+AlcoholāEster+WaterCarboxylicĀ acid+AlcoholāEster+Water.
Amphipathic refers to a molecule or structure that has both hydrophilic (water-attracting) and hydrophobic (water-repelling) regions. These molecules often have distinct polar and nonpolar parts within their structure. The term is frequently used in the context of biological molecules, such as lipids.
LCAT Ā¼ lecithin cholesterol acyltransferase
ApoC-IIIĀ raises plasma triglycerides through inhibition of LPL, stimulation of VLDL secretion, and is a novel factor in modulating intestinal triglyceride trafficking. ApoC-III also stimulates inflammatory processes in the vasculature and in the pancreas.
Apolipoprotein CII (apo CII)Ā plays an important role in plasma lipid metabolism as an activator for lipoprotein lipase (LPL). This fact is illustrated by the massive hypertriglyceridemia that is seen in individuals with inherited defects in the synthesis of apo CII.
OxPL: oxidized phospholipids, AVR ā Aortic Valve Replacement.
Lipoprotein (a)Ā or LP(a) is a type of LDL (ābad cholesterolā). A second protein called apolipoprotein or apo(a) loops around it in segments called kringles. Apolipoprotein makes the LDL particles stickier. As a result, LP(a) builds up in blood vessels, increasing the risk of cardiovascular problems. High levels of LP(a) are a risk factor for atherosclerosis.
While diet and certain lifestyle choices can affect HDL and LDL levels, your genes determine your LP(a) levels. Some people inherit gene changes (mutations) that make them more prone to high LP(a) levels. These people have a higher risk of heart disease at a young age.
microsomal triglyceride transfer proteinĀ (MTP),
Niemann-Pick C1- like 1 protein (NPC1L1)
acyl-CoA cholesterol acyl transferase (ACAT), Via Thoracic Duct Lymph vessel sends CM to Blood
The uptake of cholesterol and plant sterols from the intestinal lumen into intestinal cells is facilitated by a sterol transporter, Niemann-Pick C1- like 1 protein (NPC1L1) (Figure 6). Ezetimibe, a drug which inhibits intestinal cholesterol and plant sterol uptake, binds to NPC1L1 and inhibits its activity. Once in the intestinal cell the cholesterol and plant sterols may be transported back into the intestinal lumen, a process mediated by ABCG5 and ABCG8, or converted to sterol esters by which attaches a fatty acid to the sterol.
ABCG1Ā ATP binding cassetteĀ subfamily G member 1
TheĀ ATP-binding cassette transportersĀ ABCA1Ā and ABCG1 areĀ responsible for the major part of macrophage cholesterolĀ effluxĀ to serum or HDL in macrophageĀ foam cells,
Exogenous pathway of lipid metabolism:
This is the transport from of cholesterol and TG from food or intestine to the storage sites or adipose and other tissues. The remaining portion of the lipoprotein that remains after Lipoprotein lipase activity is called Chylomicron remnantā (rich in cholesterol), which re-enters circulation and is taken up by the liver. The remaining cholesterol is either stored for future use or excreted as bile from liver
Ā
Endogenous pathway of lipid metabolism:
This is the transport of cholesterol that is produced by liver. The process begins whenever body requires lipids. Whenever the cells require cholesterol, They increases the number of LDL receptors in the cell membrane The LDL particles circulating in the blood are engulfed inside the cell and free cholesterol is released for utilization. Once demand is met, cell decreases the number of receptors and intake of LDL particles is reduced to normal.
Ā
Reverse cholesterol transport:
The process starts with the formation of HDL. HDL carries excess cholesterol from peripheral tissues (Arteries)to deposit them in the liver. Thus the lipid transport pathway ensures that a constant balance is maintained between biosynthesis, utilization and transport of various lipids
Ā a Secreted PCSK9 binds to LDLR on the liver cell surface and mediates the lysosomal degradation of the complex formed by PCSK9, LDLR, and LDL
