Lipoproteins Flashcards
(36 cards)
What are Lipoproteins?
Chylomicrons, VLDL, LDL, HDL
- they carry lipid in blood in a way that does not impact oncotic pressure
What is Albumin?
Most abundant protein in the blood
How are Lipoproteins made?
- exogenous fat (diet lipids) from intestines to other tissues by chylomicrons
- endogenously synthesized lipid from liver to other tissues by VLDL, LDL
What is the composition of Lipoproteins?
- they are spherical particles made up of lipids and proteins (apolipoproteins)
Order the lipoproteins from smallest/heaviest to largest/lightest
- high density lipoproteins (HDL)
- Low density lipoproteins (LDL)
- intermediate density lipoproteins (IDL)
- Very low density lipoproteins (VLDL)
- Chylomicrons
- Density is proportional to the protein content and inversely proportional to the lipid content
Name the chromosome number for each of these Lipoproteins:
- AI
- CII
- B100
- B48
- E
- (a)
- chromosome 11
- chromosome 19
- chromosome 2
- chromosome 2
- chromosome 19
- chromosome 6
What are functions of Apolipoproteins?
- essential structural component of lipoproteins
- provide recognition sites for cell-surface receptors
- facilitate the transfer of lipids between lipoprotein classes
- enzyme activators (LPL)
- determine direction of transport (to periphery or to liver)
What is the exogenous and endogenous pathway of lipid transport?
Your body uses lipoproteins (protein + lipid complexes) to transport lipids (like triglycerides and cholesterol) through the aqueous bloodstream. There are two main pathways:
🥗 Exogenous Pathway – Dietary Lipid Transport
“Exogenous” = coming from outside (your diet)
🔄 Steps:
1. Dietary fat intake (TG, cholesterol)
Lipids are ingested and emulsified by bile salts in the small intestine.
2. Absorption & chylomicron formation
Inside enterocytes (intestinal cells), lipids are repackaged into chylomicrons, which are rich in triglycerides and contain Apo B-48.
3. Chylomicrons enter lymphatics
Via lacteals, they bypass the liver initially and enter the bloodstream via the thoracic duct into the left subclavian vein.
4. Peripheral tissue delivery
In the bloodstream, chylomicrons receive Apo C-II and Apo E from HDL.
Apo C-II activates lipoprotein lipase (LPL) on capillary endothelial cells (mainly in adipose, heart, and muscle), breaking down TG → FFA + glycerol.
5. Chylomicron remnants
After delivering triglycerides, remnants (still containing cholesterol) are taken up by the liver via Apo E binding to hepatic receptors.
🏭 Endogenous Pathway – Liver-made Lipid Transport
“Endogenous” = produced inside (by the liver)
🔄 Steps:
1. Liver synthesis of VLDL
Liver packages triglycerides and cholesterol into VLDL (very-low-density lipoproteins), containing Apo B-100.
2. VLDL in bloodstream
VLDL receives Apo C-II and Apo E from HDL.
3. Triglyceride delivery
Like chylomicrons, VLDL uses LPL (activated by Apo C-II) to offload triglycerides to tissues → becomes IDL (intermediate-density lipoprotein).
4. IDL fate:
* Some IDL is taken up by the liver via Apo E.
* Some is converted into LDL after further TG loss.
5. LDL delivers cholesterol
LDL (rich in cholesterol, with Apo B-100 only) binds to LDL receptors on peripheral cells and the liver to deliver cholesterol.
What is the role of HDL?
🧼 Cleanup – Role of HDL
* HDL participates in reverse cholesterol transport:
* Picks up excess cholesterol from tissues.
* Returns it to the liver for disposal or recycling.
* Donates Apo C-II and Apo E to chylomicrons and VLDL.
Chart describing different Lipids
Why does the body need Triglycerides?
🔋 1. Energy Storage and Supply
* Triglycerides (TGs) are the main form of stored energy in the body.
* When delivered to:
* Muscle → TGs are broken down into fatty acids for ATP production, especially during fasting or exercise.
* Adipose tissue → TGs are stored for future energy use.
✅ TGs are more energy-dense than carbohydrates or proteins (9 kcal/g vs. 4 kcal/g), making them an ideal long-term energy store.
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🛠️ 2. Fuel for Specific Tissues
* Heart muscle prefers fatty acids over glucose for energy.
* Skeletal muscle also uses fatty acids during rest and prolonged activity.
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🧱 3. Structural and Functional Roles
* Fatty acids from TGs are used to build:
* Phospholipids for cell membranes.
* Myelin sheaths for neurons.
* Signaling molecules like prostaglandins.
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🩺 Clinical Perspective:
* In starvation, stored triglycerides are mobilized to provide energy.
* In diabetes, TG metabolism can be impaired, leading to dyslipidemia.
* In obesity, excessive TG storage leads to metabolic problems.
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🧠 Summary:
Triglycerides are the body’s energy currency for storage and long-term use, especially vital for muscles, the heart, and during fasting states. Delivering them ensures that cells can store or burn fat as needed.
In diabetes, TG metabolism can be impaired, leading to dyslipidemia how?
🔑 First, Know the Players:
🧬 Insulin – the hormone that:
* Tells cells to store energy.
* Inhibits fat breakdown (lipolysis) in fat tissue.
🔓 Hormone-sensitive lipase (HSL) – the enzyme that:
* Breaks down stored triglycerides in adipose tissue into free fatty acids (FFAs) and glycerol.
* Releases FFAs into the blood for use as fuel.
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🔁 Normal Situation (with good insulin sensitivity):
1. After eating → insulin levels go up.
2. Insulin inhibits HSL → stops fat breakdown.
3. Triglycerides in fat stay stored.
4. Fewer FFAs are released into the blood.
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⚠️ In Insulin Resistance (like in type 2 diabetes):
1. Insulin is present, but doesn’t work well.
2. It fails to inhibit HSL properly.
3. So, HSL becomes overactive → starts breaking down triglycerides in adipose tissue.
4. More free fatty acids (FFAs) are released into the bloodstream.
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🧪 Why Does This Matter?
* Liver takes in those FFAs and turns them into triglycerides → then secretes more VLDL (a TG-rich lipoprotein).
* This contributes to:
* ↑ blood triglycerides
* Atherogenic dyslipidemia
* Fatty liver (hepatic steatosis)
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🧠 Summary:
In insulin resistance, insulin can’t suppress fat breakdown, so hormone-sensitive lipase stays active, leading to ↑ free fatty acids in blood → ↑ liver triglyceride production → ↑ VLDL → hypertriglyceridemia.
What is the steps of Microsomal Triglyceride Transfer Protein (MTTP) or abetalipoproteinemia?
🧬 What is MTTP?
MTTP = Microsomal Triglyceride Transfer Protein
A protein in enterocytes (intestine) and hepatocytes (liver) that helps assemble and transfer triglycerides onto apolipoproteins like Apo B to form:
* Chylomicrons (in the intestine) * VLDL (in the liver)
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🦠 What is MTTP Deficiency?
🧬 Inherited disorder → autosomal recessive
Known as abetalipoproteinemia (Bassen-Kornzweig syndrome)
🔧 What goes wrong?
* MTTP doesn’t work → triglycerides can’t be loaded onto Apo B-48 or B-100
* So:
* No chylomicrons made in enterocytes
* No VLDL made in the liver
* Leads to almost no Apo B-containing lipoproteins in plasma (chylomicrons, VLDL, LDL)
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🚫 Impaired Chylomicron Transfer (Exogenous Pathway)
Normally:
* Dietary TGs absorbed → reassembled in enterocytes → packed into chylomicrons with help of MTTP → secreted into lymph → blood
In MTTP deficiency:
* TGs and cholesterol are absorbed but can’t be assembled into chylomicrons
* They accumulate in enterocytes → lipid-laden intestinal cells (seen on biopsy)
* Severe fat malabsorption occurs
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🚫 Impaired VLDL Secretion (Endogenous Pathway)
* In hepatocytes, TGs can’t be assembled into VLDL
* ➡️ ↓ plasma triglycerides, cholesterol, and Apo B
* ➡️ Liver can’t export lipids → risk of fatty liver
What is difference between Chylomicrons and VLDL?
🔁 How They’re Similar:
✅ Both:
* Carry triglycerides through the bloodstream
* Are TG-rich lipoproteins
* Use Lipoprotein Lipase (LPL) to deliver fatty acids to tissues
* Shrink as they lose TGs and form remnants
📦 Clinical tie-in:
* In diabetes or obesity, you can get too much VLDL → hypertriglyceridemia
* In MTTP deficiency, you get no chylomicrons or VLDL
What does it mean when VLDL becomes LDL after TG removal?
Step-by-step:
1. VLDL is secreted by the liver, full of triglycerides (TGs).
2. In the bloodstream, Lipoprotein Lipase (LPL) acts on VLDL:
* Removes TGs and gives fatty acids to muscle or adipose tissue.
3. As it loses triglycerides, VLDL shrinks and changes:
* → becomes IDL (Intermediate-Density Lipoprotein)
* Then further TG loss leads to → LDL (Low-Density Lipoprotein)
🧬 Why does this happen?
* VLDL starts as a triglyceride-rich particle.
* As TGs are removed, the relative cholesterol content increases.
* LDL ends up being cholesterol-rich, and low in triglycerides.
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🧠 LDL = “Cholesterol Delivery Truck”
* LDL carries mostly cholesterol to tissues.
* It’s taken up by cells via LDL receptors (Apo B-100 is the key for this).
* This is how cells get cholesterol for:
* Membranes
* Hormones
* Bile acids
⚠️ If LDL isn’t cleared properly → it stays in blood → oxidized LDL → atherosclerosis
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📦 Summary:
VLDL loses triglycerides → becomes LDL.
Think of VLDL as a fat-rich truck, and as it unloads, it becomes smaller and cholesterol-dense, turning into LDL, which delivers cholesterol to cells.
Why does LDL get delivered to cells? (isn’t it bad?)
🧬 Is cholesterol delivery to cells a good thing?
✅ Yes — in moderation and in the right context.
* Cholesterol is essential for your body:
* Makes cell membranes strong and fluid
* Needed to make steroid hormones (like cortisol, estrogen, testosterone)
* Used to make bile acids (for fat digestion)
* Required for vitamin D synthesis
LDL’s job is to deliver this cholesterol to cells that need it. So, in that sense, LDL is doing a good thing.
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⚠️ So why is LDL called “bad cholesterol”?
It’s called “bad” **only when there’s too much LDL in the blood, or it’s not cleared properly by cells.
What goes wrong:
* Excess LDL stays in the blood
* LDL gets oxidized
* Oxidized LDL gets taken up by macrophages → become foam cells
* Foam cells build up in artery walls → atherosclerosis (plaque) → heart attacks, strokes
So it’s not that LDL = bad, but too much LDL or dysfunctional LDL = bad outcome
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🧠 Analogy:
* LDL = delivery trucks carrying cholesterol to cells.
* If you have the right number of trucks, they deliver safely.
* If you have too many trucks on the road, or they crash (oxidize), you get traffic jams (plaques in arteries).
What is process of Chylomicron synthesis and maturation?
🧬 What Are Chylomicrons?
* Large lipoproteins made in the small intestine
* Transport dietary triglycerides, cholesterol, and fat-soluble vitamins via the lymph → bloodstream
* Contain Apo B-48, and later acquire Apo C-II and Apo E
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🏗️ Chylomicron Synthesis (Inside Enterocytes)
Step-by-step:
1. Dietary lipids (mainly triglycerides) are digested in the gut:
* TGs → monoglycerides + free fatty acids
* Absorbed by enterocytes in the small intestine
2. Inside enterocytes:
* Lipids are re-esterified back into triglycerides in the smooth ER
* Apo B-48 is synthesized in the rough ER
3. Assembly:
* Microsomal Triglyceride Transfer Protein (MTTP) helps load triglycerides and cholesterol onto Apo B-48
* Forms nascent (immature) chylomicrons
4. Transport:
* Packaged into vesicles → move into the Golgi → secreted via exocytosis
* Enter lacteals (lymphatic capillaries in the villi) → into thoracic duct → bloodstream
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🌟 Maturation (In the Bloodstream)
1. Nascent chylomicrons enter the blood (still not fully functional)
2. From HDL, they acquire:
* Apo C-II → activates Lipoprotein Lipase (LPL)
* Apo E → required for remnant clearance by the liver
3. Now it’s a mature chylomicron: ready to deliver fat!
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🚛 Function of Mature Chylomicron
* LPL (activated by Apo C-II) on capillary endothelium breaks down TGs → free fatty acids + glycerol
* FFAs go to muscle (for energy) or adipose tissue (for storage)
* After losing TGs, the chylomicron shrinks and becomes a chylomicron remnant
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🏁 Chylomicron Clearance
* Remnants are taken up by the liver
* Via Apo E binding to hepatic remnant receptors
Do ApoE and ApoC-II come from HDL?
Yes — ApoE and ApoC-II come from HDL!
When nascent chylomicrons (freshly made in the intestine) enter the bloodstream, they are incomplete and need to “borrow” helper proteins from HDL to become functional.
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🔄 Here’s how it works:
1. Nascent chylomicrons made in the intestine only have:
* Apo B-48
2. Once in the bloodstream, they interact with HDL.
3. HDL transfers:
* Apo C-II → needed to activate lipoprotein lipase (LPL)
* Apo E → needed for liver to recognize and clear chylomicron remnants
This makes the chylomicron fully functional → now it’s called a mature chylomicron.
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🧠 Why does HDL do this?
* HDL acts like a reservoir or donor of apolipoproteins
* It shares apoproteins with other lipoproteins (like chylomicrons and VLDL) to help them function
What happens to excess Glucose turning into FFA?
💥 Starting Point: Excess Glucose
When you eat more carbohydrates (glucose) than your body needs for immediate energy:
1. Glucose → Acetyl-CoA in the liver
2. Acetyl-CoA → Fatty acids (FAs) via de novo lipogenesis
3. Fatty acids + glycerol → Triglycerides (TGs)
4. TGs get packed into VLDL particles
5. VLDL is secreted into the blood → here’s where the chain starts…
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🔁 What Happens to VLDL in the Blood?
1. VLDL carries triglycerides to tissues
* Uses Lipoprotein Lipase (LPL) (activated by Apo C-II from HDL)
* TGs → Free fatty acids (FFAs) + glycerol
2. The tissues (like adipose or muscle) take up the FFAs
3. After losing TGs, VLDL becomes:
* IDL → then
* LDL = now mostly carrying cholesterol
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🔚 What Happens to LDL?
* If your tissues need cholesterol: LDL binds to LDL receptors and is taken up → ✅ normal
* But if you have too much LDL, or it stays too long in the blood:
* It can get oxidized → OxLDL
* OxLDL is taken up by macrophages → they turn into foam cells
* Foam cells → atherosclerotic plaques
Glucose can become fat. Fat is packaged into VLDL, and excess VLDL → LDL → plaque, especially in insulin resistance or diabetes.
What is insulins role in Fatty acids?
When insulin is working properly, here’s what happens in fat cells (adipocytes):
1. Insulin tells fat cells to:
* 🚫 Stop breaking down fat (inhibits Hormone-Sensitive Lipase, or HSL)
* ✅ Take in glucose from blood (via GLUT4 transporter)
* ✅ Use that glucose to make fat (lipogenesis)
So, insulin is anti-lipolytic — it prevents fat breakdown.
⚠️ In Insulin Resistance:
Now imagine insulin can’t signal properly (like in Type 2 diabetes or metabolic syndrome):
1. Fat cells don’t respond to insulin well
* ↓ Less glucose uptake
* ↓ Less fat storage
* ❗️ Loss of insulin’s brake on HSL
2. Hormone-Sensitive Lipase (HSL) stays active
* HSL breaks down stored triglycerides → releases free fatty acids (FFAs) into the blood
3. More FFAs go to the liver, which:
* Converts them into triglycerides
* Packages those TGs into VLDL
* → You get hypertriglyceridemia, and eventually more LDL
What are characteristics of LDL?
- carry 70% of plasma cholesterol
- ApoB-100 is the major apolipoprotein
- lasts longer in circulation that VLDL
What is the fate of LDL?
- 60% gets taken up by liver LDL receptor via recognition of ApoB-100
(Apo-B -100 is a weaker ligand for the LDL receptor than ApoE = slower reuptake) - 40% is taken up by peripheral tissues also containing ApoB-100 receptors (adrenal cortex and gonads for steroid synthesis)
- LDL is also oxidized and taken up by scavenger receptors on macrophages, this is the formation of foam cells and atherosclerotic plaques (hence bad cholesterol)
Which lipoprotein is strongly associated with higher risk of coronary heart disease?
Apo(a)
Lp(a)
What is the steps of Receptor-mediated endocytosis of LDL?
Step-by-Step: Receptor-Mediated Endocytosis of LDL
- LDL binds to LDL receptor (LDLR)
- LDL has Apolipoprotein B-100 (ApoB-100) on its surface
- LDL receptor (LDLR) on the cell membrane recognizes ApoB-100
- Binding occurs especially in clathrin-coated pits (specialized membrane areas)
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- Endocytosis (LDL + receptor pulled into cell)
- The cell membrane forms a vesicle around the bound LDL
- Vesicle enters the cell → becomes an endosome
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- Receptor and LDL Separate in the Endosome
- The endosome becomes acidic
- This causes:
- LDL to detach from its receptor
- LDL receptors to be recycled back to the membrane
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- LDL Sent to Lysosome
- The LDL particle is delivered to a lysosome
- Lysosomal enzymes break LDL down:
- Cholesteryl esters → free cholesterol
- Proteins → amino acids
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- Cholesterol Used by Cell
- The free cholesterol is used for:
- Membranes
- Hormones
- Or stored as cholesteryl esters by ACAT (Acyl-CoA:cholesterol acyltransferase)
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📉 BONUS: How the Cell Regulates Cholesterol
If the cell has enough cholesterol:
* ↓ LDL receptor expression (via downregulating SREBP pathway)
* ↓ HMG-CoA reductase (less cholesterol made)
* ↑ ACAT activity (to store excess cholesterol)
Familial Hypercholesterolemia = mutation in LDL receptor → can’t clear LDL from blood → very high LDL → early atherosclerosis
