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Question 1

What is the ester group in cholestrol ester formed between?

Answer 1

carboxylate group of a fatty acid and the hydroxyl group of cholesterol.

Question 2

Why is cholestrol converted into cholestrol ester?

Answer 2

To more efficiently transport both dietary and synthesized cholesterol

Question 3

Why do HDLs change shape from disk shape to a more spherical shape?

Answer 3

Because of the accumulation of cholesterol esters in the HDL which are more hydrophobic leading them to go to the inside of the HDL which causes the spherical shape

Question 4

What is the main dietary source of cholesterol

Answer 4

From chylomicron remnants
Animal products – eggs

Question 5

How much does the body excrete cholesterol per day

Answer 5

Excrete – 1 g/day (bile acids)

Question 6

What are three sources of Cholesterol from extra-hepatic tissues?

Answer 6

Reverse cholesterol transport via HDL
Chylomicron remnants
IDL

Question 7

What does Licthen-cholestrol Acyltransferase (Lcat) do?

Answer 7

Takes a fatty acid from phosphatidylcholine and adds it to Cholestrol which results in it becoming an ester cholestrol.

Question 8

What is the role of Cholestrol ester transfer protein (CETP)?

Answer 8

CETP mediates the transfer of cholesteryl esters from HDL to other lipoproteins, such as low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL).

Question 9

What molecule is the starting point of cholestrol synthesis and Where in the cell does the synthesis take place?

Answer 9

Starting molecule: Aceytl CoA

Place: Cytoplasm

Question 10

What are the 4 main components that are needed for cholestrol synthesis?

Answer 10

Source of carbon atoms = acetyl CoA from:
ß-oxidation of fatty acids.
Dehydrogenation of pyruvate.
Oxidation of ketogenic amino acids.

Reducing power = NADPH (reduced).
Generated by enzymes in pentose pathway.

ATP energy.

Oxygen

Question 11

How much cholestrol is synthesized in the liver on avergae per day?

Answer 11

1/g per day

Question 12

What is the general outline of the 4 steps of cholestrol synthesis?

Answer 12

SI: Forms HMG-CoA from Acetyl CoA

SII: Convert from C6 to C5 intermediate. Forms activated 5 carbon intermediates (isoprenoids)

SIII: Six isoprenoids form squalene

SIV: Cyclization of squalene
squalene + O2 form cholesterol

Question 13

What is the rate limiting step in cholestrol synthesis?

Answer 13

HMG-CoA reductase.

HMG-CoA –> mevalonic acid (C6)

Question 14

What are the three different regulatory mechanisims involved in the regulation of HMG-CoA reductase?

Answer 14

1. phosphorylation by cAMP-dependent protein kinases inactivates the reductase.
2. Half life of about three hours, the amount of cholestrol effects the half life
3. Gene expression the amount of cholestrol effects the mRNA.

Question 15

How can the phosphorylation of HMG-CoA reductase be reversed?

Answer 15

2 specific phosphatases.

Question 16

What hormone induces phosphatases for the activation of HMG-CoA reductase?

Answer 16

Insulin

Question 17

Does the fed or fasted state promote cholestrol synthesis?

Answer 17

Fed

Question 18

What hormone induces adenyl cyclase for the inhibtion of HMG-CoA reductase?

Answer 18

Glucagon stimulates adenyl cyclase producing cAMP

cAMP activates protein kinase A
Inactivates HMG-CoA reductase

Question 19

How is the Synthesis of LDL receptors effected by cellular levels of cholestrol?

Answer 19

downregulate LDL receptor synthesis if the cellular levels are high

Question 20

What are the similarties and differences between ACAT and LCAT?

Answer 20

Similar: Both catalyze the formation of Cholestrol Esters.

Difference: ACAT does it for storage of cholestrol

LCAT does it for HDL and transport of cholestrol

Question 21

What are three methods of cholestrol degredation?

Answer 21

Execretion with feces (1/g day)

Conversion to bile 50%

Bacterial reduction to neutral sterols

Question 22

What type of medications are used to treat hypercholestrolism and hod do they work?

Answer 22

Type:Statins

Function: decrease HMG-CoA reductase activity by competing with it

and indirectly increasing LDL receptor synthesis

Question 23

What are two examples of statins?

Answer 23

Mevacor (Lovastatin)

Liptor

Mevacor, so doesnt want to go to the core of the HDL

Question 24

What causes familial Hypercholesterolemia (FH)?

Answer 24

LDL receptor deficiency
Gene for LDL-receptor on chromosome 19
No gender difference
Mutation is recessive

Question 25

What is the percentage of **heterozygous familial Hypercholestrolisim** and another consquence of it ?

Answer 25

**Percentage:** 1/250 **Another consquence:**premature CAD

Question 26

What is the percentage of **heterozygous familial Hypercholestrolisim** and another consquence of it ?

Answer 26

**Percentage:** 1/1,000,000 **Extremely** high LDL-cholesterol **Another consequence:**Very early symptomatic CAD

Question 27

What is the treatment of **Heterozygous** Familial hypercholestrolisim?

Answer 27

Dietary interventions, weight loss, exercise Cholesterol lowering-drugs In combination with diet will cause up-regulation of LDL-receptors Most powerful **statins** at highest dosage will result in ~60% reduction in LDL-C

Question 28

What is the difference between primary and conjugated bile acids?

Answer 28

**Primary** bile acids Bile acids that haven't bound to amino acids Good emulsifying agents **All OH groups on same side** pKa = 6 (partially ionized) ==== **Conjugated** bile salts Amide bonds **with glycine or taurine** Very good emulsifier

Question 29

How do fibrates such as **Gemfibrozil** effect bile excertion and the gall bladder?

Answer 29

**Causes:** increased biliary cholesterol excretion **Might result in:** Gall stones | **Gem**fibrozil, Gems like stones, so gallstones.

Question 30

What are the general steps of primary bile acid synthesis?

Answer 30

Hydroxylation Cytochrome P-450/mixed function oxidase system Side chain cleavage Conjugation

Question 31

What are the general steps of secondary bile acid synthesis?

Answer 31

Intestinal bacterial modification Deconjugation Dehydroxylation Deoxycholic acid Lithocholic acid

Question 32

Where are the Enzymes which produce steroid hormones from cholesterol located in the cell?

Answer 32

mitochondria and smooth ER.

Question 33

What are the biosynthetic precursor of all steriod hormones after cholestrol?

Answer 33

Progestins

Question 34

What is the rate-limting step in steroid homrone sythesis and what enzyme regulates it?

Answer 34

**Step:** transport of free cholesterol from the cytoplasm into mitochondria. **Enzyme:** Steroidogenic Acute Regulatory Protein (StAR).

Question 35

What causes congenital adrenal hyperplasia and what are some clinical signs?

Answer 35

**Cause:**21a-Hydroxylase Deficiency **Signs:** increased ACTH secretion which causes Adrenal gland hyperplasia Excess androgens

Question 36

How is the most common type of adrenal hyperplasia (21a-hydroxylase deficeny) diagnosed?

Answer 36

Diagnosis of the most common type (21-hydroxylase deficiency) is by **finding increased plasma [17-hydroxyprogesterone]** as early as 4 days after birth.

Question 37

What are the effects of **11 B -Hydroxylase Deficiency**?

Answer 37

**Increased** production of 11-deoxycortisol and 11-deoxycorticsterone. **Symptoms:** salt retention, volume expansion, and hypertension.