Cholesterol and lipoproteins Flashcards
What is the importance of cholesterol?
1) Froms the structure of the membrane
2) It is a precursor of steroid hormone and bile acids
- They are an essential molecule but not required from the diet as it is readily synthesized denovo from acetyl-CoA (derived from oxidative reactions)
- All of the reduction reaction of cholesterol biosynthesis uses NADPH as a cofactor
How is the cholesterol transported through the body?
In the form of lipoproteins in the circulation
Describe the structure of cholesterol
1) It is a lipid (hydrophobic)
2) It has four rings (provides the cell membrane with fluidity)
3) It has a polar head (faces the ECF)
4) Usually found as esters combined with fatty acids from the polar head side (which makes them easier to transport and to pack)
Where does the biosynthesis of cholesterol take place?
In the cytoplasm and microsomes (ER) found in the liver and intestine
What is the rate-limiting step in the biosynthesis of cholesterol?
The conversion of HMG-CoA into Mevalonate
- The rate-limiting enzyme is the HMG-CoA reductase
What are the first two steps in the biosynthesis of cholesterol?
1a) 2 Acetyl-CoA molecules condense together forming Acetoacetyl-CoA, via the enzyme thiolase
1b) Acetoacetyl-CoA will further condense with Acetyl-CoA yielding b-hydroxy-b-methylglutaryl-CoA via the enzyme HMG-CoA synthase
2) HMG-CoA is converted to mevalonate via the enzyme HMG-CoA reductase, which requires 2 molecules of NADPH as a cofactor (this enzyme is bound to the endoplasmic reticulum)
How is the cholesterol ester formed?
In the liver converting cholesterol to a more hydrophobic form
1) in the liver
- The enzyme acyl-CoA-cholesterol acyl transferase (ACAT), adds a fatty acid into the polar (OH) group
2) Extrahepatic
- The enzyme lecethine-CoA-cholesterol acyl transferase (LCAT), adds a fatty acid into the polar (OH) group
How is the biosynthesis of cholesterol regulated?
- By controlling the rate-limiting step
1) Short-term regulation
- Inhibited by phosphorylation, where the enzyme AMP-Dependent protein kinase (activated when ATP is low “مافي داعي نصرف عالتصنيع لما ما يكون عنا طاقة”)
2) Long-term regulation
- By the varied formation and degradation of HMG-CoA reductase, HMG-CoA has a sterol domain that activates the degradation enzyme
What is a lipoprotein?
A solubilized lipid-protein complex that contains
1) Dietary cholesterol and triglycerides
2) Synthesized triglycerides and cholesterol by the liver
These complexes contain triacylglycerol lipid droplets + cholesteryl esters, surrounded by a polar phospholipid and proteins (apo-proteins)
How is cholesterol degraded?
It is converted to bile acids which will then get eliminated through feces
What are the different types of lipoproteins?
From lowest to highest densities:
1) Chylomicron
2) Very low-density lipoproteins (VLDL)
3) Intermediate-density lipoprotein (IDL)
4) Low-density lipoprotein (LDL)
5) high-density lipoprotein (HDL)
What is the function of Intermediate density lipoproteins?
They are the precursors of LDL
What is the function of chylomicrons?
Transports exogenous TRIGLYCERIDES from the bloodstream to the adipose tissue
What is the function of very low-density lipoproteins?
Transport of endogenous triglycerides, from the liver to the adipose tissue
What is the function of high-density lipoproteins?
It transports cholesterol from the tissues to the liver
What is the function of Low-density lipoproteins?
It is essentially the VLDL but once the TG’s are removed it becomes IDL and then once the apo-proteins C-2 AND E are removed it becomes LDL
- LDL can be integrated into the tissues as an energy source, or degraded by the liver
Which lipoprotein has the highest percentage of cholesterol?
Low-density lipoproteins
What is an apoprotein?
- The major component of lipoproteins
- Classified alphabetically (A-E)
- It is responsible for the recognition of the lipoprotein by different tissues
Which lipoprotein has the highest percentage of TG’s?
Chylomicrons
Which lipoprotein has the highest percentage of protein and phospholipids?
High-density lipoproteins
Which apo-protein is present in chylomicrons?
B-48 (synthesized by the intestine)
Which lipoprotein does not have the apo-protein B?
High-density lipoproteins
Describe the life cycle of chylomicrons
- They’re lipoproteins that are made in the intestine, rich in TG’s, but also contain cholesterol and fat-soluble vitamins
- Before entering the capillaries to transfer its TG’s to the adipose tissue, Apo-C2 (activate lipoprotein lipase) and Apo-E (for it to be detected by the liver) are transferred to it from HDL
- In the capillaries, LPL transfers all of the TG’s into the tissues and the Apo-C2 is returned back to the HDL leaving us with a chylomicron remnant
- The chylomicron remnant will bind to the liver and it will be endocytosed
Describe the life cycle of VLDL, IDL, LDL
- The liver will secret the nascent TG-rich VLDL (containing endogenous TG’s, Apo-E, & Apo-B-100) it will then interact with HDL to get Apo-C2 generating a mature HDL
- In the capillaries, its TG’s are taken into the fatty tissue where the LPL takes all of the TG’s leaving us with IDL
- Apo-C2 and Apo-E are returned back to the HDL leaving us with an LDL
- LDL (carries cholesterol ester mainly) can be either integrated into the muscles for energy or degraded by the liver
