Exam 4 L3: Cholesterol and Cholesterol Esters

Question 1

What are the three things cholesterol can be turned into?

Think of the flowchart

Answer 1

Cholesterol:

1. Steroid hormones
2. Bile Salts
3. Cholesterol Esters

Question 2

Cholesterol:

Component of cell _____

Precursor of _____ acids

Precursor of ____ hormones

Answer 2

Cholesterol:

• Component of cell membrane
• Precursor of bile acids
• Precursor of steroid hormones
• endocrine tissues
• stored as cholesterol ester

Question 3

Dietary cholesterol and dietary TAGs are packaged into _______.

Answer 3

Dietary cholesterol and dietary TAGs: chylomicrons

Question 4

Synthesized Cholesterol and sythesized TAGs are packaged into ____

Answer 4

Synthesized cholesterol and TAGs are packaged into VLDLs

Question 5

Explain how acetyl-coA, cholesterol, TAGs and VLDLs are all related (think of the flow chart)

Answer 5

Question 6

What is an important intermediate in cholesterol biosynthesis?

How is it formed?

Answer 6

Mevalonate is an important intermediate in cholesterol biosynthesis

It is formed in a rxn catalyzed by HMG-CoA reductase, the rate limiting enzyme in cholesterol biosynthesis

Question 7

What is the rate limiting enzyme in cholesterol biosynthesis?

Answer 7

Rate limiting enzyme in cholesterol synthesis:

HMG CoA Reductase

Question 8

Explain how we go from acetyl coA to cholesterol

Answer 8

Question 9

Explain the effects of the following on HMG CoA Reductase:

1. Statins
2. Cholesterol

Answer 9

Statins (a type of drug) inhibit HMG CoA Reductase

Cholesterol inhibits HMG CoA Reductase through end product feedback inhibition

Question 10

Explain how one goes from mevalonate (C6) to squalene (C30)

Answer 10

Mevalonate (6C)gets phosphorylated 3 x and then decarboxylated to form Isopentenylpyrophoshate (5C)

Then it gets rearranged to 3,3 Dimethylallylpyrophosphate (5C)

Then it gets added to form Farnesylpryophosphate (15C)

Then those get added together to form Squalene (30C)

Remember: MIDFS (“michigan internet does fucking suck”

Question 11

How does squalene become cholesterol?

Squalene is 30 carbons, cholesterol is 27?

Answer 11

Squalene >>>>> lanosterol>>>> cholesterol

You remove three methyls

Rearrange a double bond

Add a new OH group

Question 12

What is the product formed by HMG-CoA reductase?

Answer 12

Mevelonate (6C) is formed by HMG CoA reductase

Question 13

What activates and inhibits HMG CoA Reductase?

Answer 13

HMG CoA Reductase is activated by insulin

HMG-CoA Reductase is inhibited by:
- Mevalonate and Cholesterol via feedback inhibition (they both inhibit the enzyme and increase its degradation)

• AMP and Glucagon also inhibit this (low energy)

Question 14

Explain how the following things inhibit HMG-CoA Reductase:

1. Cholesterol
2. Mevalonate
3. AMP and Glucagon

Answer 14

Regulation of HMG Co-A Reductase:

• Sterols (cholesterol) bind to SRE’s and inhibit mRNA production/at the transcription level
• Levalonate inhibits HMG CoA Reductase at the translation level (inhibits translation of mRNAs)
• Enzyme Stability: Degradation promoted by its products (mevalonate, cholesterol)
• Phosphorylation: Inhibition (AMP, Glucagon)

Question 15

What is the rate limiting enzyme in bile acid synthesis?

Answer 15

Rate limiting enzyme in bile acid synthesis:

7-alpha-hydroxylase

Takes cholesterol and makes bile acids

Question 16

What is the rate limiting enzyme of cholesterol ester synthesis?

Answer 16

ACAT

Question 17

Explain bile acids in the body: What do they do essentially?

We create ____ a day

We excrete _____ a day

We need ____ a day

How do we make up the difference

Answer 17

Bile acids help emulsify fats in the small intestine and facilitate their absorption

We make 0.8 g per day

We excrete 0.8 g per day

We need anout 20-30 g per day, so they get facilitated around and around

Question 18

Cholesterol————> Bile acids

Which enzyme does this?

Answer 18

7-alpha-hydroxylase

Question 19

_______ act as detergents

The are amphiphillic

Answer 19

Bile acids act as detergents

THey are ampiphillic

Question 20

Statins inhibit which enzyme?

Answer 20

Statins inhibit HMG CoA Reductase

Which takes HMG-CoA and turns it into mevalanoate, and eventually to cholesterol

Question 21

Cholesterol Esters are essentially ______ (their function)

Which enzyme turns cholesterol into a cholesterol ester?

Answer 21

Cholesterol esters are essentially cholesterol storage

ACAT is the enzyme that turns cholesterol into cholesterol esters

Question 22

Excess Cholesterol leads to _______ cholesterol synthesis and promotes cholesterol _______

______ HMG CoA Reductase

______ ACAT

______ 7-a-hydroxylase

Answer 22

Excess cholesterol leads to inhibition of cholesterol synthesis and promotion of cholesterol utilization

Inhibit HMG-CoA Reductase

Activates ACAT

Activates 7-a-hydroxylase

Question 23

Cholesterol Deprevation Leads to ____ of cholesterol synthesis and ____ of cholesterol utilization

_______ HMG CoA Reductase

_______ ACAT

_______ 7-a-hydroxylase

Answer 23

Cholesterol Deprevation Leads to activation of cholesterol synthesis and inhibition of cholesterol utilization

Activates HMG CoA Reductase

Inhibits ACAT

Inhibits 7-a-Hydroxylase

Question 24

Bile acids are formed in the ____ from ______

Answer 24

Bile acids are formed in the liver from cholesterol

Question 25

Identify the vitamin that derives from a cholesterol like precursor

Answer 25

Vitamin D derives from squalene (a cholesterol precursor)

Question 26

Identify some of the steroid hormones that cholesterol is a precursor of

Answer 26

Steroid Hormones Derived from Cholesterol:

cortisol

testosterone

aldosterone

progesterone

estradiol

Question 27

Squalene is formed from two molecules of______

Answer 27

Squalene is formed from two molecules of

farensyl pyrophosphate