Hardman - Cholesterol

Question 1

Isoprenes

Answer 1

Consist of terpenes and steroid

Plant pigments and odors

5-Carbon initiator Unit in Synthesis of Cholesterol

Question 2

Prenylation

Answer 2

Attachment of farnesyl or geranylgeranyl group

Act as anchor to membranes

Question 3

What two molecules begin synthesis of ketons and cholesterol?

Where does this occur?

Answer 3

Acetoacetyl CoA + Acetyl CoA

=

HMG-CoA

Cytoplasm

Question 4

What is the commited step in cholesterol formation?

Answer 4

Synthesis of mevalonate

Question 5

What is the rate limiting enzyme in cholesterol formation?

Answer 5

HMG-CoA Reductase

(catlyzes HMG-CoA to Mevalonate)

Question 6

What is mevalonate converted to?

Answer 6

5-carbon IPP (isopentenyl pyrophosphate)

Question 7

What is IPP isomerized to?

How many ATP does this require?

Answer 7

IPP isomerized to dimethylallyl pyrophosphate

Requires 3 ATP

Question 8

How many molecules of IPP are required to form squalene?

What are the intermediates during multiple condensations?

What is total ATP required?

Answer 8

Six IPP’s are condensed to form squalene

Dimethylallyl

I

Geranyl

I

Farnesyl

I

Squalene

18 ATP Total

Question 9

Start to finish: Cholesterol Synthesis

Answer 9

Acetoacetyl CoA+Acetyl CoA

I

HMG-CoA

***I (HMG-CoA Reductase)***

Mevalonate

I

5-P Mevalonate

I

IPP

I

Dimethylallyl

I

Geranyl

I

Farnesyl

I

Squalene

I

Lanosterol

I

Cholesterol

Ah! Ah! Help Me Plan In Diet Good Food Stay Low in Cholesterol

Question 11

How is cholesterol synthesis regulated?

Answer 11

HMG-CoA Reductase rate limiting enzyme

Four methods:

1. Sterol Dependent
   
   • (excess cholesterol binds SCAP, blocks release of SREBP)
2. Sterol Independent
   
   • Phosphorylated HMG CoA Reductase
3. Hormonal
   
   • Activate: Insulin
   • Inhibit: Glucagon/Epinephrine
4. Inhibition by Drugs
   
   • Statins (w/side effects)

Question 12

What are the major plasma lipoproteins from least dense to most dense?

Answer 12

Least: Chlyomicron

VLDL

IDL

LDL

Most: HDL

Question 13

Chylomicron

Answer 13

Largest lipoprotein

Dietary fat transport

Question 14

VLDL

Answer 14

Endogeneous fat transport

Question 15

IDL

Answer 15

LDL precursor

Question 16

LDL

Answer 16

Cholesterol transport

Question 17

HDL

Answer 17

Reverse cholesterol transport

Question 18

How do the intestines and liver package cholesterol (and fats) to enter the capillaries?

How do extra hepatic tissues transport cholesterol to the liver?

Answer 18

Intestines: Chylomicrons

Liver: VLDL

Extrahepatic: HDL

Question 19

What apolipoprotein is unique to chyolomicrons?

Where are enzymes for chylomicrons located?

What adds apo E and apo C

Answer 19

B-48

Smooth ER

Circulating HDL

Question 20

What enzyme hydrolyses TAG to FAs + Glycerol?

What activates?

What removes chylomicron remnants?

Answer 20

Lipoprotein Lipase

Activate: Insulin

Liver clears remnants

Question 21

What lipoproteins have the most TAG content?

Answer 21

Chylomicron highest TAG % (least dense)

HDL have lowest TAG % (most dense)

Question 22

What apolipoproteins tag VLDL?

Answer 22

B-100

C-11

Question 23

What happens to apolipoprotein lipase C and E following degradation?

Answer 23

Returned to HDL

Question 24

What is tag is recognized for uptake of IDL and LDL?

How many isoforms are there?

What are results of defects in each?

Answer 24

apo E

E2, E3, E4

E3: Familial Hyperlipoproteinemia (high cholesterol), early athersclerosis

E2: Reduce Alzheimers

E4: Increase Alzheimers

Question 25

Degradation of Cholesterol: Sterol Nucleus

Answer 25

Converted to bile acids

Question 26

Degradation of Cholesterol: Cholesterol

Answer 26

Secreted into gall bladder

Question 27

Degradation of Cholesterol: Futher uses?

Answer 27

Synthesis of sterol hormones

Question 28

What can excess cholesterol lead to in the gall bladder?

Answer 28

gall stones

Question 29

Excess cholesterol forms what?

Answer 29

Bile acids, bile salts

Question 30

What is the rate limiting step of steroid synthesis?

Answer 30

Conversion of cholesterol to pregnenolone

Question 31

What is the order of steroid synthesis?

Answer 31

Cholesterol I Pregnenolone I Progrestagens I 1. Glucocroticoids 2. Mineralcorticoids 3. Androgens

Question 32

What are androgens converted to?

Answer 32

Testosterone and Estradiol

Question 33

What are estrogens and testosterone vital for?

Answer 33

Reproduction and physical development

Question 34

What are progestins vital for?

Answer 34

Maintenance of pregnancy

Question 35

What are two sources of Vitamin D? What occurs during deficiency?

Answer 35

Sunlight and Supplementation Children: Ricketts Adults: Osteoperosis

Question 36

How does thermogenesis in BAT occur?

Answer 36

Low T activates cascade for **thermogenin and UCP-1** to uncouple ETC, releasing heat

Question 37

What is the rate limiting step of steroid formation?

Answer 37

Cholesterol (C27) to Pregnenolone (C21)

Question 38

Vitamin D is converted to its active form where?

Answer 38

Kidney (Vit D to Calcitriol)