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Y2S1CVSBIOCHEM > Cholesterol and lipoproteins > Flashcards

Cholesterol and lipoproteins Flashcards

1
Q

What is the importance of cholesterol?

A

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
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2
Q

How is the cholesterol transported through the body?

A

In the form of lipoproteins in the circulation

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3
Q

Describe the structure of cholesterol

A

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)

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4
Q

Where does the biosynthesis of cholesterol take place?

A

In the cytoplasm and microsomes (ER) found in the liver and intestine

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5
Q

What is the rate-limiting step in the biosynthesis of cholesterol?

A

The conversion of HMG-CoA into Mevalonate

  • The rate-limiting enzyme is the HMG-CoA reductase
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5
Q

What are the first two steps in the biosynthesis of cholesterol?

A

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)

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5
Q

How is the cholesterol ester formed?

A

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
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5
Q

How is the biosynthesis of cholesterol regulated?

A
  • 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
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5
Q

What is a lipoprotein?

A

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)

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6
Q

How is cholesterol degraded?

A

It is converted to bile acids which will then get eliminated through feces

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7
Q

What are the different types of lipoproteins?

A

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)

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8
Q

What is the function of Intermediate density lipoproteins?

A

They are the precursors of LDL

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8
Q

What is the function of chylomicrons?

A

Transports exogenous TRIGLYCERIDES from the bloodstream to the adipose tissue

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9
Q

What is the function of very low-density lipoproteins?

A

Transport of endogenous triglycerides, from the liver to the adipose tissue

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10
Q

What is the function of high-density lipoproteins?

A

It transports cholesterol from the tissues to the liver

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10
Q

What is the function of Low-density lipoproteins?

A

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
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11
Q

Which lipoprotein has the highest percentage of cholesterol?

A

Low-density lipoproteins

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11
Q

What is an apoprotein?

A
  • The major component of lipoproteins
  • Classified alphabetically (A-E)
  • It is responsible for the recognition of the lipoprotein by different tissues
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12
Q

Which lipoprotein has the highest percentage of TG’s?

A

Chylomicrons

13
Q

Which lipoprotein has the highest percentage of protein and phospholipids?

A

High-density lipoproteins

14
Q

Which apo-protein is present in chylomicrons?

A

B-48 (synthesized by the intestine)

14
Q

Which lipoprotein does not have the apo-protein B?

A

High-density lipoproteins

15
Q

Describe the life cycle of chylomicrons

A
  • 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
16
Q

Describe the life cycle of VLDL, IDL, LDL

A
  • 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
17
Q

What is the main constituent of LDL?

A

cholesterol ester

17
Q

Describe the mechanism of LDL, Receptor-mediated endocytosis

A

1) Apo-B100 is recognized by the LDL receptor on the membrane of the organ

2) The LDL is then coated with a vesicle

3) An endosome will digest everything but the cholesterol ester and return the LDL receptor back to the membrane

4) The cholesterol could then be used to make fatty acids, amino acids, or stored by the ACAT enzyme,

5) It will inhibit the synthesis of cholesterol (HMG-CoA reductase enzyme and the synthesis of LDL receptors

18
Q

What is the fate of the cholesterol in the LDL?

A

1) Amino acids

2) Fatty acids

3) Stored via ACAT (acyl-CoA-cholesterol acyl transferase)

19
Q

What are the main constituents of HDL?

A

1) Cholesteryl ester

2) Phospholipids

19
Q

What is inhibited when the cholesterol content of LDL enters the liver?

A

1) Synthesis of cholesterol via HMG-CoA reductase enzyme

2) Synthesis of LDL receptors

20
Q

Describe the life cycle of HDL

A

1) The liver will produce nascent HDL to the bloodstream where it picks up cholesterol and fatty acids from the peripheral tissues and gets converted into HDL3 (immature), where the LCAT (Lecithin cholesterol acyl transferase ads an apo A-1 to it

2) HDL3 will mature into HDL2 where the LCAT enzyme will add Apo A-1 to it, HDL2 is mature

3) Cholesterol ester transfer protein will then integrate the various apo proteins into the VLDL

21
Q

What is the lipoprotein Lpa?

A

An atherogenic (forms fatty plaques in the arteries) family of lipoproteins, consisting of LDL and protein A, has an unknown function

  • Their Apo-protein A is covalently linked to apo-B-100 via a disulfide linkage
  • It has possessed a high risk as it is associated with premature coronary artery disease and stroke
21
Q

What are the various functions of HDL?

A

1) Transfers proteins to other lipoproteins

2) Picks up the lipids from other lipoproteins

3) Picks up cholesterol from the cell membrane

4) Converts cholesterol to cholesterol ester via the LCAT reaction

5) Transfers cholesterol esters to other lipoproteins, which transports them to the liver (reverse cholesterol transport)

22
Q

Which enzyme is responsible for the transfer of apo-proteins from HDL to VLDL?

A

Cholesterol ester transfer protein

23
Q

What are the different types of dyslipidemia in Fredrickson’s classification?

A
  • Fredrickson classification divides the primary dyslipidemias into 6 categories (1, 2a, 2b, 3, 4, & 5)

1) Hyperchylomicronemia (Type-1)

2) Familial Hypercholesterolemia (Type 2a)

3) Familial combined hypercholesterolemia (Type 2b)

4) Dysbetalipoprotenemia (Type 3)

5) Familial hypertriglyceridemia (Type 4)

6) Familial lipoprotein lipase deficiency (Type 5)

24
Q

Which lipoprotein and which lipid fraction is increased in hyperchylomicronemia?

A

Increased lipoprotein is:

  • Chylomicrons

The increased lipid fraction is:

  • Triglycerides
25
Q

Which lipoprotein and which lipid fraction is increased in familial hypertriglyceridemia?

A

Increased lipoprotein is:

  • VLDL

The increased lipid fraction is:

  • Triglycerides
26
Q

Which lipoprotein and which lipid fraction is increased in Familial hypercholesterolemia?

A

Increased lipoprotein is:

  • LDL

The increased lipid fraction is:

  • Cholesterol
27
Q

Which lipoprotein and which lipid fraction is increased in dysbetalipoproteinemia?

A

Increased lipoprotein is:

  • IDL

The increased lipid fraction is:

  • Cholesterol
  • Triglycerides
28
Q

Which lipoprotein and which lipid fraction is increased in Familial combined hypercholesterolemia?

A

Increased lipoprotein is:

  • LDL & VLDL

The increased lipid fraction is:

  • Cholesterol
  • Triglycerides
29
Q

Which lipoprotein and which lipid fraction is increased in familial lipoprotein lipase deficiency?

A

Increased lipoprotein is:

  • VLDL
  • Chylomicrons

The increased lipid fraction is:

  • Cholesterol
  • Triglycerides
30
Q

How do statins lower blood cholesterol?

A

Via the inhibition of HMG-CoA-Reductase enzyme

31
Q

How do fibrates lower the levels of TAG in the blood?

A

Via the inhibition of lipoprotein lipase

32
Q

Fredrickson classification addresses primary or secondary dyslipidemia?

A

Primary

33
Q

In which type of hyperlipoproteinemia is the VLDL lipoprotein increased?

A

1) Familial combined hypercholesterolemia

2) Familial hypertriglyceridemia

3) Familial lipoprotein lipase difciency

34
Q

In which type of hyperlipoproteinemia is cholesterol increased (only cholesterol)?

A

Type 2a familial hypercholesterolemia

Y2S1CVSBIOCHEM (6 decks)

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