Lipoprotein Metabolism: An Overview

Functions of Lipoprotein 

Lipoproteins transport lipids in blood because lipids are nonpolar and float in blood, coalescing into large clumps that can clog small capillaries.

Amphipathic substance

It is used to transport any non-polar substance in a polar medium. Amphipathic substances contain both polar and nonpolar groups. Amphipathic substances in polar mediums have polar groups facing the exterior and nonpolar groups facing the interior to keep nonpolar lipids together. A lipid particle is attached to the apoprotein. The lipid part of the lipoprotein will have an Amphipathic outer layer and encloses a nonpolar lipid core in the center. Cholesterol and phospholipids will be on the outer portion whereas the inner portion is covered with cholesterol ester and triacylglycerol.

Examples of Amphipathic lipids

• Cholesterol: polar, OH group present and has a complex non-steroidal structure.
• Phospholipids : The phosphate group is negatively charged and is considered polar.

Also read: Hyperlipoproteinemia & Fatty Liver: An Overview

Functions of Apoproteins:

1. They act as ligands for receptors. Example

• Apo E which is accepted by remnant receptors.
• Apo B 100 is accepted by LDL receptors.
• Remnant receptors are very specific and accept only lipoproteins with Apo E as an apoprotein.
• LDL receptors accept either Apo E or Apo B100 as apoprotein.
• Act as regulators for the enzymes for cholesterol metabolism. For example, Apo C2 activates lipoprotein lipase and Apo A1 activates LCAT and Apo C3 inhibits lipoprotein lipase.

Chylomicrons

Functions of Chylomicron

Chylomicrons carry exogenous or dietary triacylglycerols from the intestine to extrahepatic tissues. It bypasses the liver due to its large size and enters lymphatics → thoracic duct → left subclavian vein → systemic circulation → extra hepatic tissues

Metabolism of Chylomicrons

• Formed in enterocytes and are released into the circulation with some apoproteins (Apo B48)
• Chylomicrons with only Apo B48 are called nascent chylomicrons.
• After acquiring Apo C2 and Apo E from HDL, nascent chylomicron → functional chylomicron.

Also read: Amino Acids And Proteins Chemistry Solved Question

Major Functions of HDL

HDL takes part in reverse cholesterol transport, which is collecting phospholipids and cholesterol ester from extrahepatic tissues and delivering it to the liver. It also acts as a repository for all the apoproteins and helps in recycling apoproteins. Lipoprotein lipase is clinging to the vessel valve held in place with heparin sulfate (present in large vessel walls like the aortic wall). Lipoprotein 

lipase acts on chylomicrons triacylglycerol → fatty acid and glycerol

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Fatty acids cross the vessel wall endothelium and extrahepatic tissue membranes, enter extrahepatic tissues, and are stored as triacylglycerol.

(Glycerol reaches liver as it is the only organ that can use glycerol because it has glycerol 3 kinase)

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Chylomicron can't retain ApoC2 and gives it back to HDL and becomes chylomicron remnant

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All remnants together reach the liver, gets accepted by either LDL or remnant receptors

VLDL Metabolism

VLDL transports endogenous triacylglycerols from the liver to Extrahepatic tissue. VLDL is formed in liver or hepatocytes and released as nascent VLDL(inactive) into circulation Apoproteins present in nascent VLDL are Apo B100, inactive Apo C2 and Apo E. HDL helps convert nascent VLDL to functional VLDL by activating inactive Apo C2. Active Apo C2 activates LPL, which cleaves VLDL-TAG to form glycerol and fatty acids. Glycerol is used by liver and fatty acids is stored as TAG in extrahepatic tissues

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Fate of VLDL

If VLDL loses its Apo C2 immediately to HDL, it is called a VLDL remnant. VLDL remnant is accepted by the liver through the LDL receptor or remnant receptor. The VLDL remnant contains Apo B100 and Apo E. If VLDL does not lose its Apo C2, retains its Apo C2, goes through multiple cycles of LPL activity, loses a major chunk of TAG, and then loses its Apo C2, now its size is reduced and density is increased; this is called IDL (Intermediate Density Lipoproteins).

IL

Fate of IDL

The apoproteins present in IDL are Apo B100 and Apo E. IDL reaches the liver after being accepted from a remnant or LDL receptor. When IDL encounters HDL (reverse cholesterol transfer - rich in cholesterol ester), two exchange reactions occur:

a. Cholesterol ester transfer protein transfers all cholesterol esters from HDL to IDL.

b. IDL gives back Apo E to HDL.

IDL becomes LDL which is a cholesterol ester-rich lipoprotein with only Apo B100 protein.

LDL

LDL gets either accepted by LDL receptors of the liver or by LDL receptors of extrahepatic tissues.

Also read: Hartnup Disease and Glycine Metabolic Effects

HDL Metabolism

HDL is formed by both enterocytes and hepatocytes. Liver HDL has its own lipoproteins, while intestinal HDL obtains its lipoproteins from the liver. After HDL gets released into circulation, all the HDL particles will have only cholesterol and phospholipids. Apo A1 apoprotein then attaches to the HDL. HDL is formed in the liver and intestine and takes a discoidal shape because phospholipids and cholesterol (amphipathic) cannot form a core, so they form a discoid shape. Apo A1 activates LCAT in discoidal HDL, transferring the fatty acid from lecithin to cholesterol.

This process results in the formation of cholesterol ester, a nonpolar lipid. Cholesterol ester will form a central core and get surrounded by phospholipid and cholesterol. Finally, the discoidal HDL will get converted to spheroidal HDL.3. Therefore, LCAT converts the discoidal HDL to spheroidal HDL3.

Functions of spheroidal HDL3

The apoprotein present is Apo A1. Apo A1 activates ABC A1 (enzyme along the membranes of extrahepatic tissues). ABC A1 collects cholesterol ester and phospholipids from all extrahepatic tissue membranes by using ATPs; this cholesterol is added to HDL 3, which increases the size and density decrease of it. This large HDL is called HDL2.

Fate of HDL2

It reaches the liver and gets bound with scavenger receptor B1 which has hepatic lipase activity. It extracts the contents of HDL2. Therefore, reducing its size and forming HDL3 again. When other remnants reach the liver, they bind with a receptor and the cell engulfs the whole

remnant's lipoprotein. This is known as the HDL cycle/reverse cholesterol transport.

Also read: INI-CET High Yield Questions For Biochemistry

Intermediate Stage in Between the Conversion of HDL2 to HDL3

Pre-beta HDL (most active form) becomes discoidal HDL Apo A1

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activates LCAT (converts cholesterol into cholesterol ester, which forms spheroidal core)

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Discoidal HDL to spheroidal HDL

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ABC1 activates and gets converted to HDL2, reaching the liver.

The membrane of HDL2 is made up of cholesterol, phospholipids, and other lipoproteins. Excess membrane will be present and gets pinched off as pre-HDL. Phospholipids and cholesterol are attached to Apo A1. LCAT deficiency leads to low HDL concentrations, which leads to hypoalpha proteinemia. Lipoprotein X (characteristic shape taken up by discoidal HDL) is the feature of LCAT deficiency and obstructive jaundice. In obstructive jaundice, bile salts accumulate. Also, Bile Salts are Amphipathic and take lamellar structures; they look like lipoprotein X

Clinical Features of LCAT Deficiency

There are 2 forms of LCAT deficiency.

1. Partial LCAT Deficiency: Looks as fisheye disease
2. Complete LCAT Deficiency: Looks like fisheye disease along with hemolytic anemia and CKD (because of accumulation of lipoprotein X in mesangium) and early myocardial infarction

Also read: Fanconi Anemia: Symptoms, Causes and Treatment

Important Points to Remember

1. Chylomicron transports exogenous/dietary triacylglycerols from the intestine to extrahepatic tissues.
2. Lipoprotein lipase is activated by Apo C2
3. Lipoprotein lipase is inhibited by Apo C3
4. LCAT is activated by Apo A1
5. The most active form of HDL is pre-HDL

Important MCQs

Q. The main function of lipoprotein is to

1. Activate fatty acid synthesis.
2. Transport lipids to kidney for excretion
3. Stimulate lipolysis.
4.  Transport lipids in blood between tissues

Q. Apo A1 activates

1. Lipoprotein lipase
2. Lecithin Cholesterol Acyl Transferase
3. Hormone Sensitive Lipase
4. LRP

Q. Apo C3 activates.

1. Lipoprotein Lipase
2. Lecithin Cholesterol Acyl Transferase
3. Hormone Sensitive Lipase
4. LRP

Also read: Last 5 Years PYQs INI-CET Biochemistry

Q. Chylomicron transports triacylglycerol from intestine to

1. Liver
2. Kidney
3. Extrahepatic tissues
4. Brain

Q. The apoprotein which activates Lipoprotein lipase is

1. Apo B48
2. Apo B100
3. Apo C2
4. Apo A1

Q. The apoprotein present in nascent chylomicron is

1. Apo B100
2. Apo B48
3. Apo C2
4. Apo E

Q. True regarding chylomicron are all except:

1. HDL is involved in activation of chylomicron.
2. LPL helps in the conversion on chylomicron to chylomicron remnant
3. Chylomicron remnants reach the Extrahepatic tissues.
4. Chylomicron reaches the Extrahepatic tissues.

Aslo read: NEET PG Previous Year Question Papers of Last 7 Years

Q. Remnant receptor accepts lipoproteins with which of the following apoproteins?

1. Apo E
2. Apo B100
3. Both
4. None

Q. LDL receptor accepts lipoproteins with which of the following apoproteins?

1. Apo E
2. Apo B100
3. Both
4. None

Q. Which of the following helps in the conversion of discoidal to spheroidal HDL?

1. LPL
2. LCAT
3. ABCA 1
4. CETP

Q. Regarding HDL all are true, except:

1. HDL is synthesised by liver and intestine.
2. Pre beta HDL is the most active form
3. Mutation in ABC-1 causes Tangier's disease.
4. Both liver and intestine HDL have Apo C and Apo E

Also read: Last 5 Year PYQs in Biochemistry for NEET PG

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