Name: Beenish Mujahid
Roll no.:1282-RE-BS-MB-21
Semester: 6th
Subject: Biochemistry
Topic: Very Low Density Lipoprotein
Submitted to : Sir Hamid Mukhtar
Contents
Introduction.................................................................................................................................................3
Composition............................................................................................................................................3
Function...................................................................................................................................................3
Importance..............................................................................................................................................3
Overview of lipoproteins.............................................................................................................................3
Structure of a lipoprotein........................................................................................................................3
Types of lipoproteins...............................................................................................................................3
Chylomicrons.......................................................................................................................................3
VLDL.....................................................................................................................................................3
IDL........................................................................................................................................................4
LDL.......................................................................................................................................................4
HDL......................................................................................................................................................4
Structure and composition of VLDL.............................................................................................................4
Core.........................................................................................................................................................4
Surface(hydrophilic shell)........................................................................................................................4
Composition of VLDL...............................................................................................................................4
Biosynthesis process................................................................................................................................5
Synthesis of lipids................................................................................................................................5
ApoB-100 Synthesis.............................................................................................................................5
Lipidation of ApoB-100(Pre-VLDL Formation)......................................................................................5
Maturation in the Golgi.......................................................................................................................5
Secretion in the bloodstream..............................................................................................................5
Metabolism of VLDL....................................................................................................................................5
VLDL enter circulation.............................................................................................................................5
Lipoprotein lipase activation...................................................................................................................5
Formation of IDL (intermediate density lipoprotein)...............................................................................5
Formation of LDL.....................................................................................................................................6
Clearance.................................................................................................................................................6
Role of Apolipoproteins in VLDL function....................................................................................................6
ApoB-100.................................................................................................................................................6
ApoC-II.....................................................................................................................................................6
ApoE........................................................................................................................................................6
Clinical significance of VLDL.........................................................................................................................6
VLDL is a cardiovascular threat................................................................................................................6
VLDL in Hyperlipidemia............................................................................................................................6
It’s a marker of insulin resistance and metabolic syndrome...................................................................6
Dietary modifications..............................................................................................................................7
Physical activity.......................................................................................................................................7
Conclusion...................................................................................................................................................7
Very Low Density Lipoprotein
Introduction
It is one of the five types of lipoprotein that are made up of lipids and proteins. They are
responsible for transporting fats in blood. It is produced by liver when it packages triglycerides from
excess carbohydrates and proteins to send out to tissues for storage and energy.
Composition
The composition of VLDL is as follow. It consist of 55-65% of triglycerides, 10-15% of
cholesterol,15-20% of phospholipids and 5-10% of proteins.
Function
The main function of VLDL is to transport triglycerides from the liver to the tissues in the
peripheral regions.
Importance
Too much VLDL in blood means too many triglycerides in the blood. The presence of too many
triglycerides means increased risk of atherosclerosis, heart disease. (Ginsberg, H. N. (1998).)
Overview of lipoproteins
Hydrophobic lipids like cholesterol and triglycerides are transported through the blood's
aqueous environment by lipoproteins. Lipoproteins are complexes of lipids and proteins. They move fats
between the liver, intestine, and tissues as carriers.
Structure of a lipoprotein
It consists of hydrophobic core and a hydrophilic shell. The hydrophobic core consists of
Triglycerides and Cholesteryl esters and the hydrophilic shell is composed of Phospholipids, Free
Cholesterol, and Apolipoproteins
.
Types of lipoproteins
Chylomicrons
Its main origin is intestine. The main lipid present in Chylomicrons is triglycerides. Its major
function is to deliver dietary triglycerides to tissues.
VLDL
The liver makes a type of lipoprotein called Very Low-Density Lipoproteins (VLDL) to transport
triglycerides, cholesterol, and other lipids from the bloodstream to various tissues. They play a crucial
role in lipid metabolism and are high in triglycerides. VLDL gradually converts into intermediate-density
lipoproteins (IDL) and then low-density lipoproteins (LDL), which are frequently linked to cholesterol
transport and cardiovascular risk after delivering its triglyceride content.
IDL
When Very Low-Density Lipoproteins (VLDL) lose their triglyceride content in the bloodstream,
intermediate-density lipoproteins (IDL) form as a transitional product. IDLs are an intermediate step in
the transport of lipids and contain a mixture of cholesterol and triglycerides. Low-Density Lipoproteins
(LDL), which are primarily responsible for delivering cholesterol to tissues, are either taken up by the
liver or further converted.
LDL
Lipoproteins known as low-density lipoproteins (LDL) transport cholesterol throughout the body
from the liver to cells. Often referred to as "bad cholesterol," high levels of LDL can lead to cholesterol
buildup in blood vessel walls, increasing the risk of atherosclerosis and cardiovascular diseases. LDL is
necessary for the structure of cell membranes and the production of hormones, despite its bad
reputation; however, maintaining a healthy balance is essential.
HDL
Because they assist in transporting cholesterol back to the liver for excretion, high-density
lipoproteins (HDL) are referred to as "good cholesterol." This process protects the arteries from plaque
buildup and reduces the risk of heart disease. By regulating cholesterol levels, HDL plays a crucial role in
maintaining cardiovascular health. (Jonas, A., & Phillips, M. C. (2008).)
Structure and composition of VLDL
The spherical VLDL particle is hydrophilic on the outside and hydrophobic in the middle. It’s
designed this way so it can float in the bloodstream, carrying fats from the liver to the tissues.
Core
Its major component is triglyceride that makes up about 55 to 65 percent of VLDL particle. Triglycerides
consist of fats made by liver from excess carbohydrates or proteins. It also consists of cholesteryl esters
that are stored forms of cholesterol.
Surface (hydrophilic shell)
It consists of phospholipids, free (unesterified) cholesterol and apolipoproteins. The outer shell
is formed by an amphithatic molecule named as phospholipids. Phospholipids allow VLDL to be soluble
in blood. The free unesterified cholesterol is present in the outer layer and it also helps maintain the
structure. The apolipoproteins are functional and identifying parts of VLDL. (Gruffat, D.,
Bauchart, D. (1996).) The key ones are
Apolipoprotein Function
ApoE Helps VLDL remnants binds to liver receptor for clearance
ApoC-II Activates LPL to break down triglycerides
ApoB-100 Structural protein helps in receptors recognition
Weisgraber, K. H. (1994).
Composition of VLDL
Components Percentage
Triglycerides 55-65%
Phosopholipids 15-20%
Cholesterol(free + esters) 10-15%
Proteins(Apolipoprotein) 5-10%
Borén, J. (2006).
Biosynthesis and Secretion of VLDL
Liver is the organs that synthesize VLDL to export cholesterol and endogenous triglycerides to
peripheral tissues. It is synthesized by heptocytes found in liver specifically in smooth endoplasmic
reticulum, rough endoplasmic reticulum and Golgi apparatus.
Biosynthesis process
Synthesis of lipids
Triglycerides are made up of fatty acids and glycerol-3-phosphate.However cholesterol is
synthesized via mevalonate pathway in the smooth ER.These lipids make hydrophobic core of VLDL.
ApoB-100 Synthesis
ApoB-100 is synthesized on ribosomes present of rough ER.It forms structural backbone of VLDL.
Lipidation of ApoB-100(Pre-VLDL Formation)
In the rough ER, ApoB-100 is partially lapidated with triglycerides this is done by the help of MTP
(microsomal triglyceride transfer protein).This result in the formation of pre-VLDL.
Maturation in the Golgi
Pre-VLDL travel to the Golgi apparatus. Here it gets glycosylated and fully lipated.
Secretion in the bloodstream
Mature VLDL is packed into secretory vesicles. They are then released in the bloodstream.
(Bauchart, D. (1996).)
Metabolism of VLDL
VLDL can be considered as a fat laden ship that is launched by the liver.The journey of VLDL
involves
1. Tryglycerides delivery
2. Conversion to IDL
3. Then to LDL
VLDL enter circulation
After the entry of VLDL in blood after secretion from liver it already contains ApoB-100.Then it
picks ApoC-II and ApoE from HDL.
Lipoprotein lipase activation
ApoC-II is responsible for activating lipoprotein lipase (LPL).LPL is located on capillary walls .LPL
is responsible for hydrolyzing triglycerides in VLDL into free fatty acids and glycerol. Free fatty acids
enter into tissues for storage in adipose tissues and for energy into muscles.
Formation of IDL (intermediate density lipoprotein)
After the removal of triglycerides VLDL become IDL.IDL contains less triglycerides and more
cholesterol esters still has ApoB-100 and ApoE.IDL is transient and can undergo two possibilities.
1. Taken up by liver via ApoE mediated endocytosis
2. Converted to LDL by hepatic lipase
Formation of LDL
LDL is a cholesterol rich lipoproteins and also retains ApoB-100 .Its primary role is to deliver
cholesterol to peripheral tissues.
Clearance
LDL is either absorbed by peripheral tissue for membrane synthesis and hormonal synthesis or
taken up by liver to regulate cholesterol level. (Packard, C. J. (1994).)
Role of Apolipoproteins in VLDL function
VLDL doesn’t only carry fats it uses apolipoproteins for various reasons. Some of its functions are
to stabilize VLDL structure, activates enzymes and guide its interaction with cells. These apolipoproteins
include
ApoB-100
It is made in liver during the assembly of VLDL.It is the structural backbone of VLDL.
ApoC-II
It is acquired from HDL after VLDL enter bloodstream. Its major function is to activate
lipoprotein lipase (LPL).LPL is used to breakdown triglycerides into free fatty acids. It is also essential for
fat delivery to tissues.
ApoE
It is also acquired from HDL.It is found in liver where it act as remnant receptor. (Boren, J.
(2005).)
Clinical significance of VLDL
VLDL is a cardiovascular threat
VLDL is a brick laying mechanism for atherosclerosis. The VLDL drops off triglycerides which then
become IDL then LDL.These particles in excess trigger plaque formation and artery blockage which
increase high risk of heart attack.
VLDL in Hyperlipidemia
It is seen in type-IIb hyperlipidemia and type IV hyperlipidemia.
It’s a marker of insulin resistance and metabolic syndrome
When insulin fail liver floods the blood with LDL.These results in HDL drop, LDL get small and
meaner and triglycerides soar. (Visseren, F. L. (2021).)
Strategies to Control Elevated VLDL Levels
Dietary modifications
As liver is the place where mostly excess carbs and fats are made. So a person can reduce simple
carbs and limit saturated and trans fats. Moreover increased fibers can also be beneficial.
Physical activity
Exercise can activate LPL that breakdown VLDL.30-45 minutes of aerobic exercise and strength
training is used to increase insulin activity. (Salisbury, D. (2014).)
Conclusion
When it comes to transporting endogenous triglycerides from the liver to peripheral tissues for
energy storage and utilization, Very Low-Density Lipoproteins (VLDLs) play a crucial physiological role.
However, significant metabolic and cardiovascular conditions, such as atherosclerosis, insulin resistance,
and various forms of hyperlipidemia, are strongly correlated with their elevation in plasma. Lipid
homeostasis and disease progression are greatly improved by comprehending VLDL's composition,
biosynthesis, metabolism, and functional roles, particularly its interaction with apolipoproteins. In the
clinical setting, elevated levels of VLDL serve as both a therapeutic target and a diagnostic indicator.
Therefore, for maintaining cardiovascular health and metabolic equilibrium, effective control through
lifestyle modification, pharmacological intervention, and disease management is necessary. VLDL
continues to be a topic of study as well as a key player in contemporary clinical biochemistry with
continued education and research.
References
Ginsberg, H. N. (1998). Lipoprotein physiology. Endocrinology and metabolism clinics of North America,
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Jonas, A., & Phillips, M. C. (2008). Lipoprotein structure. In Biochemistry of lipids, lipoproteins and
membranes (pp. 485-506). Elsevier.
Gruffat, D., Durand, D., Graulet, B., & Bauchart, D. (1996). Regulation of VLDL synthesis and secretion in
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