Last edited: 9/12/2021
1. LIPOPROTEIN METABOLISM
Metabolism | Lipoprotein Metabolism | Chylomicrons, VLDL, IDL, Medical Editor: Sohani Kashi Puranic
LDL, & HDL
OUTLINE II) CLASSIFICATION OF LIPOPROTEINS
I) OVERVIEW (1) Based on Electrophoretic Mobility
II) CLASSIFICATION OF LIPOPROTEINS
III) PATHWAYS (2) Based on Density
IV) DIETARY FAT
V) CHYLOMICRON (i) Chylomicrons
VI) VERY LOW DENSITY LIPOPROTEIN (ii) Very Low-Density Lipoproteins (VLDL)
VII) LOW DENSITY LIPOPROTEIN (iii) Intermediate Density Lipoproteins (IDL)
VIII) HIGH DENSITY LIPOPROTEIN
IX) SUMMARY (iv) Low Density Lipoproteins (LDL)
X) APPENDIX (v) High Density Lipoproteins (HDL)
XI) REVIEW QUESTIONS (vi) Free Fatty Acids (FFA)/ Non-esterified Fatty
XII) REFERENCES
Acids (NEFA)
I) OVERVIEW
III) PATHWAYS
Fat absorbed from the diet and lipids synthesized by the
liver and adipose tissue must be transported between the (A) EXOGENOUS
various tissues and organs for utilization and storage. Since Exogenous lipids comprise of dietary lipids
lipids are insoluble in water, the problem of how to transport Form CHYLOMICRONS
them in the aqueous blood plasma is solved by associating
nonpolar lipids (triacylglycerol and cholesteryl esters) with (B) ENDOGENOUS
amphipathic lipids (phospholipids and cholesterol) and Endogenous lipids comprise of lipids synthesized in the
proteins to make water-miscible lipoproteins. body
[Harper] Form VLDL, IDL, LDL, HDL, FFA
IV) DIETARY FAT
LIPOPROTEIN = (A) FATS IN FOOD
LIPID + APOPROTEIN
(1) Components of fatty foods
(i) Triglycerides
(ii) Cholesterol
(iii) Cholesterol Esters
(B) PATHWAY FOR DIETARY LIPIDS
(1) Intestine
Secrete Cholecystokinin (CCK)
(2) CCK
(i) Gall bladder
CCK causes contraction of gall bladder
Leads to release of bile
(3) Bile
Figure 1. Generalized Structure of a Plasma Lipoprotein
Bile is composed of the following:
(i) Bile Salts
HDL- “GOOD CHOLESTEROL” (ii) Bilirubin
LDL- “BAD CHOLESTEROL” (iii) Water
(iv) Phospholipids
(v) Cholesterol
Bile is released into the duodenum of small intestine
LIPOPROTEIN METABOLISM METABOLISM: Note #1. 1 of 6
(4) Bile Salts (C) APOPROTEINS
(i) Components: Apo B-48
Apo A-1
(a) Hydrophobic portion- binds to lipid Apo C-II
Apo E
(b) Hydrophilic portion- interacts with water
(D) FUNCTION
(ii) Function:
Transports dietary (exogenous) TGs from intestine to
Involved in emulsification of fat adipose tissue
(E) PATHWAY
(iii) Examples: (1) Intestine
(a) Cholic acid
(b) Deoxycholic acid (2) Lacteals
(5) Pancreatic Lipase
(i) Structure & Secretion
Secreted by pancreas (3) Blood
Protein bound to it: Colipase
(ii) Function i. Apo-E
ii. Apo-C II
Breaks the ester bonds of fatty acids
(4) Capillaries
(i) Monoglycerides (MAG) Capillaries of the following have a special enzyme:
(ii) Free Fatty Acids (FFA) (i) Adipose tissue
(6) Micelle (ii) Skeletal Muscles
(iii) Heart
This enzyme is called Lipoprotein Lipase (LPL)
Components of a micelle:
(i) Glycerol
(i) Monoglycerides (MAG) (ii) Free Fatty Acids (FFA)
(ii) Free Fatty Acids (FFA) FFA are taken up by muscles (skeletal, cardiac) &
(iii) Vitamins A, D, E, K adipocytes
(iv) Bile acids (a) Muscles
(7) Enterocyte • FFA→ beta oxidation→ Acetyl CoA→ Kreb’s
Cycle→ ETC→ ATP
(b) Adipocytes
• FFA + Glycerol → TG
(i) Smooth Endoplasmic Reticulum (SER)
• The glycerol in adipocytes is generated by
In SER, special enzymes fuse the MAG & FFA glucose
together
This forms Triglycerides (TG)
(ii) Rough Endoplasmic Reticulum (RER)
Synthesizes Apoprotein B-48 (Apo B-48)
(5) Liver
V) CHYLOMICRON
(A) SITE OF PRODUCTION
Intestine
(B) CONTENTS (i) LDL Receptor
Triglycerides ↑↑↑ (ii) LDL Receptor Related Protein (LRP)
Cholesterol
Cholesterol Esters
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(F) FATE This enzyme is called Lipoprotein Lipase (LPL)
(i) Protein
(i) Glycerol
Broken down into amino acids
(ii) Free Fatty Acids (FFA)
(ii) TG FFA are taken up by muscles (skeletal, cardiac) &
Forms VLDL adipocytes
TG + Apoproteins + Cholesterol = VLDL
(a) Muscles
(iii) Cholesterol • FFA→ beta oxidation→ Acetyl CoA→ Kreb’s
Incorporated in liver as: Cycle→ ETC→ ATP
(a) Bile salts (b) Adipocytes
(b) Cholesterol Ester • FFA + Glycerol → TG
• Storage form • The glycerol in adipocytes is generated by
• Cholesterol is converted to Cholesterol Ester glucose
by the enzyme ACAT- Acyl Cholesterol Acyl
Transferase
(c) Cell membrane
VI) VERY LOW-DENSITY LIPOPROTEIN
(4) Liver
(A) SITE OF PRODUCTION
Liver (i) LDL Receptor
(B) CONTENTS (ii) LDL Receptor Related Protein (LRP)
Triglycerides ↑↑
Cholesterol
(F) FATE
Cholesterol Esters
(1) Liver
(C) APOPROTEINS
In liver, IDL is broken down into:
Apo B-100
Apo C-II (i) Protein
Apo E (ii) TG
(D) FUNCTION (iii) Cholesterol
Transports endogenous TG from liver to peripheral
(a) Bile salts
tissues
(b) Cholesterol Ester
(E) PATHWAY (c) Cell membrane
(1) Liver IDL is also acted upon by Hepatic Triglyceride Lipase
(HTGL)
This releases FFA & glycerol, which are used by
(i) Released from Chylomicrons the liver
(ii) Synthesized from glucose, amino acids, glycerol The remnant is transported back to the blood
where HDL takes back Apo-E
(2) Adrenal Cortex
(2) Blood
(i) LDL Receptor
i. Apo-E ↑↑↑
(ii) LDL Receptor Related Protein (LRP)
ii. Apo-C II
(3) Capillaries
Capillaries of the following have a special enzyme:
(i) Adipose tissue (i) Aldosterone
(ii) Skeletal Muscles In Zona Glomerulosa
(iii) Heart
(ii) Cortisol
In Zona Fasciculata
(iii) DHEA
In Zona Reticularis
LIPOPROTEIN METABOLISM METABOLISM: Note #1. 3 of 6
VII) LOW DENSITY LIPOPROTEIN EXCESSIVE ACCUMULATION OF LDL
Accumulates in sub-endothelial spaces
(A) SITE OF PRODUCTION LDL undergoes different reactions:
From IDL (VLDL) in blood (i) Oxidation- by ROS
(B) CONTENTS (ii) Glycation- by Glucose
Cholesterol ↑↑ This forms OXIDIZED LDL/ GLYCATED LDL
Cholesterol Esters Initiates inflammatory response
Oxidized LDL attaches to CD-36/ fatty acid translocase on
(C) APOPROTEINS macrophages
Macrophages get engorged with cholesterol to form Foam
Apo B-100
cells
(D) FUNCTION These get deposited in subendothelial space to form an
atheromatous plaque
Transports cholesterol from liver to peripheral tissues Leads to Atherosclerosis
(E) PATHWAY
VIII) HIGH DENSITY LIPOPROTEIN
(1) Blood
(A) SITE OF PRODUCTION
Intestine, Liver
(B) CONTENTS
(F) FATE Triglycerides
(1) Liver Cholesterol
Cholesterol Esters
(C) APOPROTEINS
Apo A-1
Apo A-2
Apo C-II
(i) Free amino acids Apo E
(ii) Cholesterol (D) FUNCTION
(a) Bile salts Transports cholesterol from peripheral tissues to liver
(b) Cholesterol Ester
(c) Cell membrane
(E) PATHWAY
(1) Intestine, Liver
(2) Adrenal Cortex
Synthesize Apo A-1
(2) Foam Cells
(i) Aldosterone
In Zona Glomerulosa (i) ABC A-1
(ii) Cortisol Binding of Apo A-1 to ABC A-1 causes
Cholesterol in foam cells to be taken up by
In Zona Fasciculata
nascent HDL
(iii) DHEA HDL becomes more mature (HDL 3)
In Zona Reticularis (ii) ABC G-1
(3) Gonads Mature HDL (HDL 3) with Apo A-1 binds to ABC
G-1
This causes more cholesterol uptake by the HDL,
and it is now called HDL 2
(i) Male
Testosterone
(ii) Female
Estrogen
Progesterone
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(3) Blood (2) Liver
(i) Interaction between HDL & VLDL
HDL gives Cholesterol to VLDL
VLDL gives HDL TGs
(ii) Interaction between HDL & IDL IX) SUMMARY
(iii) Interaction between HDL & LDL
Cholesterol is esterified by the enzyme LCAT
(F) FATE
(1) Adrenal Cortex, Gonads
Figure 2. Summary
X) APPENDIX
Figure 3. Lipoprotein Metabolism
LIPOPROTEIN METABOLISM METABOLISM: Note #1. 5 of 6
XI) REVIEW QUESTIONS
1) Which is called the dietary lipid?
a) LDL
b) VLDL
c) Chylomicron
d) HDL
2) LPL enzyme is present in the capillaries of all
EXCEPT:
a) Liver
b) Heart
c) Skeletal muscle
d) Adipose tissue
3) HDL interacts with IDL via which enzyme?
a) ACAT
b) LPL
c) HTGL
d) LCAT
4) Which lipoprotein has the most Cholesterol Ester
content?
a) LDL
b) VLDL
c) Chylomicron
d) HDL
5) Apo B-100 is present in which of the following
chylomicrons?
a) VLDL
b) LDL
c) IDL
d) HDL
CHECK YOUR ANSWERS
XII) REFERENCES
● Le T. First Aid for the USMLE Step 1 2020. 30th anniversary
edition: McGraw Hill; 2020.
● Marieb EN, Hoehn K. Anatomy & Physiology. Hoboken, NJ:
Pearson; 2020.
● Boron WF, Boulpaep EL. Medical Physiology.; 2017.
● Guyton and Hall Textbook of Medical Physiology. Philadelphia,
PA: Elsevier; 2021.
● van EP, Lehninger AL. Guide to Lehninger's Principles of
Biochemistry: With Solutions to Problems. New York, NY: Worth
Publ.; 1988.
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