Biochem Test 4

Front 1

Where can cholesterol/cholesterol esters come from?

Back 1

Diet
Liver Synthesis
(and LIMITED intestinal synthesis)

Front 2

What important compounds are made in the body from cholesterol? (4)

Back 2

1. Bile salts
2. Steroid Hormones
3. Blood Lipoproteins
4. Membranes

Front 3

What is the path of cholesterol entering the body from the diet?

Back 3

Transported on chylomicrons -> blood -> liver

Front 4

What are the steps in hepatic cholesterol synthesis?

Back 4

Acetyl CoA
Acetate Acetyle CoA
HMG-CoA (via HMG CoA Reductase ->)
Mevalonate
5-C Isoprene
Cholesterol

Front 5

How is hepatic cholesterol synthesis regulated?

Back 5

HMG-CoA Reductase
(HMG-CoA -> Mevalonate)

Front 6

What is the target of statin drugs? What do they do?

Back 6

HMG-CoA Reductase
Reduce cholesterol synthesis because this is the RLS.

Front 7

What is the RLS in cholesterol synthesis?

Back 7

HMG-CoA Reductase

Front 8

What are the major and minor regulations of hepatic cholesterol synthesis?

Back 8

Major:
Cholesterol (from any source) reduces the amount of HMG-CoA Reductase available.
Minor:
INSULIN activates synthesis.

Front 9

What is the signifigance of esterified cholesterol in regulation?

Back 9

Esterified cholesterol does not effect the amount of HMG-CoA Reductase.
Unesterified cholesterol does.

Front 10

The action of HMG-CoA Reductase requires what nucleotide?

Back 10

NADPH provides reducing power (donates H)

Front 11

What degrades HMG-CoA Reductase?
When is this degradation increased?

Back 11

Degraded by a protease
The protease's activity increases when cholesterol and bile salt levels are high.

Front 12

What regulation of cholesterol synthesis probably evolved to help assure adequate cholesterol levels?

Back 12

Insulin regulation of HMG-CoA Reductase

Front 13

What regulation increases cholesterol synthesis in the fed state when ATP and Acetyl-CoA supplies are plentiful?

Back 13

Insulin

Front 14

How do extra-hepatic cells normally get cholesterol?

Back 14

Usually from the liver viz LDL transport

Front 15

Is HMG-CoA Reducatase active in extra-hepatic cells?

Back 15

Not under normal conditions.

Front 16

Where can cholesterol be esterified/deesterified?

Back 16

1. On Lipoproteins
2. In Cells

Front 17

What esteriefies cholesterol on lipoproteins?
In cells?

Back 17

On lipoproteins- LCAT
In cells- ACAT

Front 18

What enzyme de-esterifies cholesterol?

Back 18

Cholesterol Esterase

Front 19

____ cholesterol is less able to leave the HDL than ____ cholesterol.

Back 19

Esterified
Unesterifies

Front 20

This lipoprotein delivers dietary triglycerides to skeletal muscle and adipocytes. It also takes cholesterol to the liver.

Back 20

Chylomicrons

Front 21

This lipoprotein delivers triglycerides made from FA synthesis in the liver and also cholesterol that has been taken to the liver .

Back 21

VLDL

Front 22

This lipoprotein delivers cholesterol to the cells. (Then it ideally cleared from the serum.)

Back 22

LDL

Front 23

This lipoprotein takes choleserol back to the liver or otherwise removes it from the bloodstream.

Back 23

HDL

Front 24

What is the significane of the different sub-types of VLDL, HDL, and LDL?

Back 24

They vary in size, some of which create more risk of coronary heart disease than others.

Front 25

What is the role of Apo CII?

Back 25

Activates LPL

Front 26

What is the function of Apo E?

Back 26

Allows lipoproteins to bind to LDL receptors on liver.

Front 27

Which lipoprotein correlates to a high risk of cornoary heart disease? Low?

Back 27

High-LDL
Low- HDL

Front 28

Dietary cholesterol reaches the liver on ____. Cholesterol leaves the liver on ____.

Back 28

Chylomicrons
VLDL

Front 29

When is triglyceride removed from FLDL and what enzyme does this?

Back 29

Removed at the adipose tissue or skeletal muscle by LPL.

Front 30

What regulates LPL's activity on chylomicrons and VLDL?

Back 30

HDL regulates this by providing Apo CII to activate LPL.

Front 31

Once the triglyceride has been removed from VLDL, the remnants are called?

Back 31

IDL

Front 32

What can happen to IDL once it is formed?

Back 32

1. Can return to the liver via LDL receptors to be degraded.
2. Can be converted to LDL

Front 33

How is LDL formed?

Back 33

Triglycerides are removed from IDL, which increases its density to LDL.

Front 34

Where are the triglycerides from IDL removed to form LDL?
What enzyme does this?
Where do these triglycerides go?

Back 34

In hepatic sinusoids.
Via HTGL (Hepatic Triglyceride Lipase)
Triglycerides are transferred to HDL.

Front 35

What is transferred from HDL to IDL as the IDL are converted to LDL?

Back 35

Cholesterol Esters

Front 36

What determines whether IDL goes back to the liver or go on to make LDL?
What is the significance of this?

Back 36

The number of IDL receptors on the liver determine the fate of the IDL.
Low hepatic cholesterol means there will be lots of IDL receptors and you ultimately wont get a lot of LDL which is a good thing.

Front 37

Why is excess LDL cholesterol bad?

Back 37

It circulates in the blood stream and is oxidized over time. It is a very large molecule and macrophages try to eat it once it is oxidized which creates a foam cell. These begin to form plaques.

Front 38

Why may Vitamin E,C,and A help reduce coronary heart disease?

Back 38

They are antioxidants so they may help reduce the oxidation of LDL leading to less plaque build up.

Front 39

How is LDL cholesterol used by extra-hepatic cells?
(How does it get into the cell and what happens to it then?)

Back 39

Enters extra-hepatic cells via LDL Receptors.
Lysosomes degrade the LDL.
Free cholesterol is released and added to the cells store either as cholesterol or cholesterol-ester.

Front 40

What inhibitory effect do high levels of cholesterol in extra-hepatic cells have?

Back 40

1. Reduce action of HMG-CoA Reductase in cell
2. Down-regulate LDL receptors on cell surface

Front 41

What limits the amount of LDL the liver takes in under normal conditions?

Back 41

Normally there aren't too many LDL receptors on the liver surface because hepatic cholesterol down-regulates the receptors.

Front 42

How is a LRP receptor different from an LPL receptor?
Where are LRP receptors found?

Back 42

Recognize a wider range of lipoproteins than LDL.
Found in liver, brain, and placental membrane surfaces.

Front 43

Unlike the LDL receptor, LRP receptor synthesis is not affected by ___.

Back 43

Cellular cholesterol levels.

Front 44

What causes Familial Hypercholeterolemia?
What is the result?

Back 44

Genetically defective LDL Receptors.
Serum cholesterol levels become elevated very early in life because cells cant take in cholesterol.

Front 45

Multifactorial Hypercholesterolemia
What is it?

Back 45

Due to a combination of dietary, behavioral and genetic factors.
Account for 95% of people with high cholesterol.

Front 46

What can cause extra-hepatic cells to start making cholesterol?
What are two causes?

Back 46

Happens when the cholesterol levels in the extra-hepatic cells arent high enough to inhibit HMG-CoA Reductase.
Two causes:
1. Defective LDL Receptors
2. Defective Cholesterol Esterase (so Esterified Cholesterol cant be deesterified)

Front 47

Why is elevated fasting serum triglyceride a risk factor for coronary heart diease?

Back 47

If you have excess VLDL in blood, then you are also going to have excess IDL and LDL. They are all interrelated.

Front 48

If you lower a patients LDL levels, what are you allowing to happen?

Back 48

Lower LDL means more VLDL can be made to IDL and subsequently to LDL. Basically you are allowing the pathway to regulate.

Front 49

Where is HDL made?

Back 49

In the liver.

Front 50

Why is HDL good?

Back 50

It returns cholesterol to the liver.

Front 51

What are SR-B1 Receptors?

Back 51

Scavenger Receptors
Take HDL back into the liver

Front 52

Are SR-B1 Receptors regulated by hepatic cholesterol levels?

Back 52

No.

Front 53

________ picks up cholesterol resulting from cell membrane degradation.

Back 53

HDL

Front 54

Most hepatic HDL uptake occurs via the ___ receptor.

Back 54

SRB-1 (Scavenger Receptor)

Front 55

What is the only means of cholesterol removal from the body?

Back 55

Bile Salt Excretion
(Bile salts are made from cholesterol)

Front 56

What is the RLS in the conversion of cholesterol to bile salts? (enzyme)

Back 56

The first step.
7-alpha-hydroxylase
Puts a hydroxyl group on cholesterol.

Front 57

Why would eating fiber help lower cholesterol levels?

Back 57

Fiber binds more bile salts so they are excreted and cholesterol is lowered.

Front 58

How does getting rid of bile salts help decrease cholesterol levels?

Back 58

Because you need bile salts so you will have to turn more cholesterol into bile salts.

Front 59

Where are bile salts made?
What are the starting compounds?

Back 59

Liver
Cholesterol, ATP, NAHPH

Front 60

Primary bile salts are ____.
1.
2.

Back 60

Unconjugated
Cholic Acid
Chencholic Acid

Front 61

The primary bile salt are conjugated to the hydrophilic compounds ____ or ____, resulting in the four conjugated bile salts.

Back 61

Taurine
Glycine

Front 62

Conjugated bile salts are made from ____.
1.
2.
3.
4.

Back 62

Primary Bile Salts

Taurocholic
Taurochencholic
Glycocholic
Glycochencholic

Front 63

What does the conjugation of bile salts do to their function/properties?

Back 63

Increases their solubility, allowing them to function as detergente

Front 64

How are secondary bile salts formed?

Back 64

Formed by bacterial action on the four conjugated bile salts once they have been secreted into the intestine.

Front 65

Bile salts and bile acids occur according to what?

Back 65

pH
(They are the same thing- above or below pKa.)

Front 66

What is Lp(a) and how does its presence in the serum relate to coronary heart disease?

Back 66

LDL plus Apo A.
Unclear what the correlation is but it is high following an MI.

Front 67

What size LDL, HDL, VLDL pose the greatest risk for coronary heart disease?

Back 67

LDL-The biggest and smallest.
HDL- Smallest
VLDL- Biggest