1) The site (Organs and subcellular localization) 2) Reactions including High quality diagrams showing the reaction with structures. 3) Pathway regulation (Key enzymes and allosteric effectors shown clearly on the pathway with different colors and/or fonts) and hormonal regulation.

1. Faculty of Pharmacy
Assignment Topic: VLDL & LDL metabolism
Course Title: Biochemistry
Course Code: PB303
Lab Group: C2
Submitted to: DR. Ahmed Maher
Prepared By: Menrva father Moisis – 170429

2. 2
1) The site:
VLDL LDL
Organs - Synthesized by the liver, but it
does not accumulate at the liver. As
it redistribute triglycerides and
cholesterol.
- Very low density lipoprotein.
- A type of lipoprotein (10%
cholesterol – 70% triglycerides –
10% proteins – 10% other fats).
- converted into LDL and IDL
(intermediate density lipoprotein) in
the blood stream
- Metabolism occurs in the liver.
- Synthesized in the liver from VLDL
metabolism, then released to the blood
stream.
- Low density lipoproteins.
- A type of lipoproteins (26%
cholesterol – 10% triglycerides – 25%
proteins – 15% other fats).
- the LDL is oxidized and migrate with
monocytes to the sub endothelial space
then become macrophages, in which it
take more and more LDL in the
oxidized form and form foam cell
within atherosclerotic plaques.
- Metabolism occurs in the liver.
subcellular
localization
Golgi apparatus Golgi apparatus

3. 3
2) Reactions including High quality diagrams showing the reaction with
structures.
 VLDL is a lipid and cholesterol carrying molecule that is produced by the liver and work
on redistributing the cholesterol and triacylglycerol.
 When VLDL is synthesized it is attached to APO B 100, this complex or attachment
called nascent VLDL, and is considered the first form produced.
 The nascent VLDL is then released to the blood stream. It interacts with HDL, which will
add APO C II and APO E to the VLDL molecule. So a mature VLDL is produced.
 The mature VLDL have three APO lipoproteins (APO C II – APO E – APO B 100). Each
one of these lipoproteins has a specific function in the metabolism process.
 The function of APO C II is to activate a protein called lipoprotein lipase.
 So lipoprotein lipase act on VLDL releasing APO C II back to HDL, then ideal or
intermediate density lipoprotein (IDL) is formed. This new formed molecule (IDL) has
the two remaining APO lipoprotein, which are the APO B 100 and APO E.
 The IDL has two pathways:
a) Interact with hepatic lipase
b) Interact with remnant receptors in the liver, and get taken back by the liver
(Kwiterovich, 2000)
 Both of these processes are going to require APO E lipoprotein, because the hepatic
lipase use APO E to activate the metabolism of IDL and the remnant receptor also require
APO E to recognize it.
 It the IDL take the pathway of the hepatic lipase, we have low density lipoproteins that
have APO B 100. The APO B 100 acts to allow the LDL to get recognized by the liver.
So now LDL can be taken up by LDL receptors in the liver and in other cells by APO B
100 to redistribute cholesterol all over the body. (Goldstein, and Brown,1977)

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5. 5

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3) Pathway regulation
Key enzyme:
The key enzymes in VLDL and LDL metabolism are lipolytic enzymes LPL and HL. When LPL
activity is raised, VLDL is rapidly removed from the circulation, and when the LPL is low the
removal of TG rich particles is stopped, which result in increment of serum TG and decrement of
HDL. Also LPL is essential in the conversion of VLDL into LDL.
Allosteric enzyme:
LPL is a normal constituent of the arterial wall. It is found that whether the lipoprotein lipase
affects:
1- Lipoprotein binding to sub endothelial cell matrix.
2- Lipoprotein transport across bovine aortic endothelial cells.
(Merkel et al, 2002)
Increased LDL binding requires the presence of LPL and was not associated with LDL
aggregation. Also, LPL increase VLDL. Lipoprotein transport across monolayers increased
during hydrolysis of VLDL TF. VLDL transport across the monolayers increased 18% and LDL
transport increased 37%, in the presence of LPL and VLDL. So LPL primarily increase the
retention of LDL and VLDL.

7. 7
The process of VLDL synthesis and degradation is complex and affected by many factors. The
main factor that affects VLDL is the apolipoprotein B 100, its degradation and formation. Also
hepatic levels of lipids as the phosphatidylcholine, choline ester, fatty acids, and triglycerides
affects the synthesis of VLDL. The phosphatidylcholine is found to promote the translocation of
Apo B from the cytoplasm to the lumen of ER, which is an important step in the early synthesis
of VLDL. In case of high levels of CE, the degradation of Apo B is suppressed and as a result
VLDL secretion increased
ATP citrate lyase:
Is a key lipogenic enzyme which is work on converting the citrate in the cytoplasm into acetyl
CoA, which is the initial factor for malonyl CoA for the biosynthesis of fatty acid. As cited by
Innerarity et al (1999), the ATP citrate deficiency leads to decrease the VLDL level in serum,
but raise the hepatic triglyceride content, resulting from the decrement of hepatic secretion of
VLDL containing Apo B 48.
Hormonal regulation:
- VLDL synthesis is affected by the insulin hormone. The insulin resistance (it is the case
when the cells of muscles and fats ignore the signals of insulin hormone). As the insulin
does not affect only the regulation of carbohydrates metabolism, but also the regulation
of lipoproteins metabolism. For example the IR is associated with the VLDL increment in
secretion. Which in order increase the synthesis of LDL which is depend in its
metabolism on VLDL. Acute increment of insulin result in the inhibition of VLDL
secretion by promoting the Apo B degradation. It is one of the anabolic properties of the
insulin. It allows the hepatic storage of the lipids rather than for its distribution in VLDL
to other tissues for fuel.
- Studies by Brown and Goldstein (1975) proved that the glucagon increment is
associated with reduce in the VLDL production.
- Sex hormones as estrogen and testosterone have no effect or very modest impact on
VLDL production.

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References:
Brown, M.S. and Goldstein, J.L., 1975. Regulation of the activity of the low density
lipoprotein. Cell, 6(3), pp.307-316.
Goldstein, L.J. and Brown, S.M., 1977. The low-density lipoprotein pathway. Annual review of
biochemistry, 46(1), pp.897-930.
Innerarity, T.L., Borén, J., Yamanaka, S. and Olofsson, S.O., 1999. Biosynthesis of
Apolipoprotein B48-containing Lipoproteins REGULATION BY NOVEL POST-
TRANSCRIPTIONAL MECHANISMS. Journal of Biological Chemistry, 271(5), pp.2353-
2356.
Kwiterovich Jr, P.O., 2000. The metabolic pathways of high-density lipoprotein, low-density
lipoprotein, and triglycerides: a current review. The American journal of cardiology, 86(12),
pp.5-10.
Merkel, M., Eckel, R.H. and Goldberg, I.J., 2002. Lipoprotein lipase genetics, lipid uptake, and
regulation. Journal of lipid research, 43(12), pp.1997-2006.
Packard, C.J., Demant, T., Stewart, J.P., Bedford, D., Caslake, M.J., Schwertfeger, G., Bedynek,
A., Shepherd, J. and Seidel, D., 2000. Apolipoprotein B metabolism and the distribution of
VLDL and LDL subfractions. Journal of lipid research, 41(2), pp.305-317.