Biochem 2-3 Cholesterol, Lipoproteins And Bile

Front 1

Cholesterol is the starting material for____,_____ and _____.

Back 1

Bile, Vitamin D, Steroids

Front 2

Cholesterol synth occurs in _____ cells.

Back 2

hepatic

Front 3

Cholesterol synthesis products:

Back 3

Cholesterol, NADP+, ADP

Front 4

What is regulated enzyme of cholesterol synth?

Back 4

HMG CoA Reductase; proteolysis of the enzyme increases as sterol levels rise.

Front 5

T/F: Cholesterol ester levels alter the rate of cholesterol synth.

Back 5

false

Front 6

At high insulin/glucagon levels, HMG CoA reductase is_______ and active.

Back 6

dephosphorylated; This signals that ATP (and acetyl CoA) are available for cholesterol synthesis

Front 7

What is glucagon's effect on HMG CoA reductase activity?

Back 7

phosphorylation and inactivation; This regulation is much less significant than decreasing HMG CoA reductase synthesis

Front 8

HMG CoA reductase is regulated pharmacologically by the_____ group of drugs which inhibit this enzyme

Back 8

statin

Front 9

LCAT occurs______ where as ACAT occurs ______.

Back 9

on lipoproteins, in cells.

Front 10

What reverses the activity of LCAT and ACAT?

Back 10

cholesterol esterase

Front 11

Why would i need to esterify cholesterol?

Back 11

for storage

Front 12

Does cholesterol ester alter LDL membrane receptor synthesis?

Back 12

no; likewise, cholesterol esters do not affect HMG CoA reductase synth.

Front 13

Where is Bile synthesized and what do you need to synthesize it?

Back 13

hepatocytes; cholesterol, ATP, NADPH

Front 14

What is the controlled step in Bile synthesis?

Back 14

7α-hydroxycholesterol production from cholesterol is feedback inhibited by high bile salt levels.

Front 15

What are the primary bile salts?

Back 15

cholic acid and chenocholic acid

Front 16

Why are primary bile acids conjugated?

Back 16

increases bile acid solubility, allowing the bile salts to function as detergents.

Front 17

What are the primary conjugated bile salts?

Back 17

taurocholic, glycocholic, taurochenocholic, and glyochenocholic acid

Front 18

Why are there secondary bile salts?

Back 18

produced by bacterial action on the four conjugated primary bile salts once the latter have been secreted into the intestine

Front 19

What are the secondary bile salts?

Back 19

deoxycholic, lithocholic, deoxychenocholic, and lithochenocholic acids

Front 20

T/F: nearly all bile salts are reabsorbed.

Back 20

true

Front 21

T/F: Cholesterol rings can be broken down in the body.

Back 21

false

Front 22

T/F: HDL levels are higher in premenopausal women than in men of the corresponding age.

Back 22

true

Front 23

Serum triglyceride levels are proportional to serum_____ levels in a fasted condition.

Back 23

VLDL

Front 24

Chylomicron Fnx:

Back 24

Deliver dietary lipids

Front 25

Chylomicron Remnant Fnx:

Back 25

Deliver dietary cholesterol to liver

Front 26

VLDL Fnx:

Back 26

Deliver endogenous lipids

Front 27

IDL Fnx:

Back 27

Return endogenous lipids to liver; precursor of LDL

Front 28

LDL Fnx:

Back 28

Deliver cholesterol to cells

Front 29

HDL Fnx:

Back 29

Reverse cholesterol transport

Front 30

Apo CII

Back 30

cofactor activator of Lipoprotein Lipase (LPL)

Front 31

Apo E

Back 31

ligand for binding of several lipoproteins to LDL and LRP receptors

Front 32

Chylomicrons occur only in the____ state. They are the only lipoproteins not synthesized in the____.

Back 32

fed, liver

Front 33

Because the contain tons of____, chylomicrons are the lightest of lipoproteins and float to the top in sample.

Back 33

TG

Front 34

Where are chylomicrons are formed? What happens to 'em?

Back 34

intestinal mucosa; they pick up dietary triglycerides and cholesterol resulting in Nascent chylomicrons which get modified in the blood.

Front 35

What happens to the nascent chylomicrons?

Back 35

HDL transfer Apo E & CII to nascents: E recognizes hepatic receptors, CII activates lipoprotein lipase

Front 36

Lipoprotein Lipase:

Back 36

Mature chylomicrons are transported to adipose and skeletal m. where LPL converts chylomicron TGs to free FAs and glycerol

Front 37

Who induces LPL synthesis?

Back 37

insulin

Front 38

Skeletal M. LPL has a____ Km for triglycerides than does adipose lipoprotein lipase.

Back 38

lower; resulting FAs enter the adipose or skeletal m. where they are stored or used for energy production. the glycerol goes to the liver.

Front 39

chyomicron remnants:

Back 39

chylomicron minus TG; go to the liver (w/ cholesterol on board) to be broken down; Dietary cholesterol is thus carried from the intestines to the liver on chylomicron remnants.

Front 40

What happens to dietary cholesterol not used by the liver?

Back 40

it is incorporated into VLDL (and subsequently LDL) along with cholesterol synthesized in the liver.

Front 41

What does VLDL do?

Back 41

VLDL are made in the liver and deliver TGs (which contain the FAs & cholesterol synthesized in the liver) to skeletal m. and adipose cells.

Front 42

What process is VLDL Fnx analogous to?

Back 42

completely analogous to that of chylomicron delivery of dietary TG to cells with HDL donation of Apo CII to VLDL to activate LPL allowing breakdown of VLDL TGs into FAs and glycerol

Front 43

VLDL becomes____ when its TGs are removed.

Back 43

IDL; As VLDL leaves the liver w/ cholesterol from the diet (chylomicron remnant delivery) and hepatic synth, LPL takes TGs away making VLDL more dense, hence IDL.

Front 44

What happens to IDL?

Back 44

goes to liver (LDL receptors) or gets degraded to LDL by hepatic TG lipase (HTGL) in hepatic sinusoids.

Front 45

What is the HDL ineraction w/ IDL?

Back 45

-IDL gives TGs to HDL and receives cholesterol esters from HDL= conversion of IDL→LDL

Front 46

What determines how much
IDL goes to the liver vs. being converted to LDL?

Back 46

hepatic cholesterol levels

Front 47

What happens to LDL?

Back 47

delivers cholesterol (originally synthesized in the liver or delivered there from the diet) to extra-hepatic cells.

Front 48

The presence of de-esterified (e.g. free) cholesterol in the cells leads to:

Back 48

-down regulation of the genes for LDL receptor synthesis
-inhibition of synthesis of HMG CoA reductase

Front 49

LDL cholesterol is utilized in the extra-hepatic cells.
Some of this cholesterol is esterified by_______.

Back 49

ACAT

Front 50

LDL Receptor-related Protein (LRP) receptors:

Back 50

provide an alternate means of LDL entry into extra- hepatic cells. These receptors recognize a wider range of lipoproteins and lipoprotein fragments than does the LDL receptor.

Front 51

How is it that LRP receptors can decrease serum lipoprotein levels? (what makes them different from LDL receptors)

Back 51

Unlike the LDL receptor, LRP receptor synthesis is not affected by cellular cholesterol levels.

Front 52

Why are antioxidant vitamins good for cholesterol metabolism?

Back 52

Excess serum LDL is oxidized by ROS allowing macrophages to eat them and turn into foam cells. Antioxidant vitamins
decrease this oxidation.

Front 53

What is the gate-keeping fnx of LDL receptors?

Back 53

Ensures that only the amount of cholesterol needed will be taken up by extra-hepatic cells.

Front 54

Why can't the excess cholesterol on LDL be taken up by the liver?

Back 54

The amount of serum cholesterol returned to the liver will be limited since it depends on cholesterol levels in the liver. These levels in turn will depend on dietary cholesterol intake and on hepatic cholesterol synthesis.

Front 55

Why can't IDL be returned to the liver instead of converted to LDL to lower elevated serum LDL levels?

Back 55

High hepatic cholesterol levels will prevent IDL return to the liver. (IDL can use hepatic IDL/ LDL receptors only to the extent these receptors are not down regulated by high hepatic cholesterol levels.) IDL will be converted to LDL in increasing amounts, further increasing serum LDL levels.

Front 56

What happens to folks w/ genetically defective LDL receptors?

Back 56

Serum LDL levels become extremely high early in life.
Accelerated atherosclerotic development and coronary heart disease results.

Front 57

What percentage of PTs w/ elevated LDL is caused by genetically defective LDL receptors?

Back 57

5%; condition is called familial hypercholesterolemia.

Front 58

T/F: HMG CoA Reductase is down regulated in PTs w/ defective LDL receptors.

Back 58

false; if LDL cholesterol cannot enter the cell: 1. HMGCoA reductase does not get repressed, 2. ACAT not stimulated, 3. LDL receptor synthesis not repressed (more broken LDL receptors made)***make sure you know this

Front 59

Name the 4 steps to pathological extra-hepatic cell synthesis of cholesterol:

Back 59

1. Cholest can't enter the cell due to genetically defective LDL receptors.
2. LDL and cholesterol levels in the cell decrease.
3. Repression of cellular HMG CoA synthesis by cholesterol does not occur. Extra-hepatic cholesterol synthesis, normally completely “turned off”, is allowed to occur.
4. Serum LDL levels simultaneously rise

Front 60

Will decreased serum LDL be measured as increased or decreased VLDL levels?

Back 60

decreased, measured as TG

Front 61

Describe HDL's use of LCAT:

Back 61

HDL pick up cholesterol resulting from cell membrane degradation and esterifies some of this cholesterol using the LCAT esterase enzyme. This esterified cholesterol is transferred to IDL, helping to create LDL.

HDL receive triglycerides from IDL in this exchange, also helping to create LDL.

Front 62

What are SR-B1 receptors for?

Back 62

HDL also return some cholesterol directly to the liver via the non-specific scavenger receptor SR-B1 which are not down regulated by high hepatic cholesterol levels.

Front 63

Bile and cholesterol sequestering drugs:

Back 63

decrease bile acid reabsorption and dietary cholesterol absorption.

Front 64

Lp(a):

Back 64

Lp(a) has been found to be elevated post-MI. It may also be elevated pre-MI and could thus serve as a risk indicator for MI. If oxidized, Lp(a) may promote atherosclerotic plaque formation.