Cholesterol Biosynthesis, Transport and Genetics 2

Question 1

Most foods that are high in cholesterol are also high in what?

Answer 1

saturated fatty acids

Question 2

Which foods increase cardiovascular disease risk?

Answer 2

foods high in saturated fatty acids aka trans-fats (dietary cholesterol intake not supported)

Question 3

What is the best dietary way to lower cholesterol?

Answer 3

eat more FIBER

Question 4

Which type of fiber is the key ingredient in cholesterol regulation?

Answer 4

soluble fiber

Question 5

Why is soluble fiber important?

Answer 5

binds cholesterol which allows it to pass through the intestinal tract instead of being absorbed

Question 6

Where does cholesterol in the body come from?

Answer 6

diet

synthesis by the body (liver and intestine)

Question 7

What are some risk factors for high cholesterol that cannot be controlled?

Answer 7

age

genes

Question 8

When do people’s bodies tend to produce more cholesterol?

Answer 8

as they AGE

Question 9

T/F: A family history of high cholesterol or heart disease INCREASES a person’s risk of developing high cholesterol.

Answer 9

true

Question 10

What are some risk factors for high cholesterol that can be controlled?

Answer 10

smoking
overweight
poor diet
sedentary lifestyle

Question 11

How does nicotine affect cholesterol?

Answer 11

lowers good cholesterol (HDL)

Question 12

How does cholesterol exist in the gut?

Answer 12

bile salts

cholesterol

Question 13

Where are bile salts produced, stored and secreted into?

Answer 13

produced in liver
stored in gall bladder
secreted into duodenum after eating

Question 14

What types of molecules are bile salts?

Answer 14

amphipathic

Question 15

amphipathic molecules that act as a surfactant to emulsify lipids in food and form micelles containing monoglycerides, phospholipids, and cholesterol

Answer 15

bile salts

Question 16

Which transporter is responsible for bringing cholesterol and other sterols across the membrane from the lumen into the enterocyte?

Answer 16

NPC1L1

Question 17

What transporter is responsible for bringing non-cholesterol sterols out of the enterocyte and back into the lumen?

Answer 17

ABCG5/G8

Question 18

What are the 5 major lipoproteins?

Answer 18

• chylomicrons
• VLDL
• IDL
• LDL
• HDL

Question 19

large particles that carry dietary lipid

Answer 19

chylomicrons

Question 20

carry endogenous triglyceride and some cholesterol

Answer 20

VLDL

Question 21

carry cholesterol esters and triglycerides

Answer 21

IDL

Question 22

carry cholesterol esters

Answer 22

LDL

HDL

Question 23

Which pathway involves the movement of cholesterol and fatty acids from the intestine , through chylomicrons, and eventually to the liver?

Answer 23

exogenous

Question 24

Which pathway involves the processing of various lipoproteins from VLDL to LDL

Answer 24

endogenous

Question 25

Which pathway is responsible for forming the different types of HDL that exist?

Answer 25

reverse cholesterol transport

Question 26

Which pathway starts with the lymph where chylomicrons are located and moves into the blood where there are lipoprotein lipases on epithelial cell surfaces on blood vessel wall that can process the chylomicrons and release FA that can be taken up by heart/muscle/adipose tissue. This produces a chylomicron remnant that gets taken up by the liver through the LDL receptor where cholesterol will be released

Answer 26

exogenous

Question 27

Which lipoproteins are involved in the ENDOgenous pathway?

Answer 27

VLDL and LDL

Question 28

In the endogenous pathway, where is VLDL formed?

Answer 28

liver from triglycerides and cholesterol esters

Question 29

In the endogenous pathway,, VLDL can be hydrolyzed by lipoprotein lipase to form what?

Answer 29

IDL or VLDL remnants

Question 30

Where do VLDL remnants go?

Answer 30

cleared from the circulation or incorporated into LDL

Question 31

LDL particles contain a core of _____ _____ and a smaller amount of __________.

Answer 31

cholesterol esters | triglyceride

Question 32

What is LDL internalized by?

Answer 32

hepatic and nonhepatic tissues

Question 33

In the liver, LDL is converted into what and secreted into what?

Answer 33

bile salts | intestines

Question 34

In non-hepatic tissues, what is the function of LDL?

Answer 34

hormone production cell membrane synthesis stored

Question 35

LDL is also taken up by _______ and other cells which can lead to excess accumulation and the formation of ____ ____ which are important in plaque formation.

Answer 35

macrophages | foam cells

Question 36

Which cells are important in plaque formation

Answer 36

foam cells

Question 37

_____ particles, produced in the liver or the intestine, initiate the efflux of cholesterol and phospholipids from cell membranes via interaction with the _________.

Answer 37

Lipid-poor preβ-HDL | ATP-transporter A1 (ABCA1).

Question 38

Subsequent action of the _____ esterifies cholesterol in preβ-HDL particles and converts them to mature α-HDL particles.

Answer 38

lecithin-cholesterol acyl transferase (LCAT)

Question 39

How can mature HDL deliver cholesterol to the liver?

Answer 39

- directly via the Scavenger Receptor Type B1(SR-B1) | - indirectly by exchange of cholesterol esters by the cholesterol ester transfer protein to Chylomicrons, VLDL or LDL.

Question 40

The uptake of apoB-rich particles occurs via ____ ___ ______(approximately 50% of RCT).

Answer 40

hepatic LDL Receptors

Question 41

The ______ of TG in TG-rich HDL by hepatic lipase and endothelial lipase leads to a smaller HDL which re-enters the RCT cycle.

Answer 41

lypolysis

Question 42

includes family history and HIGH LDL cholesterol

Answer 42

Familial Hypercholesterolemia (F+H=FH) (homozygotes most impacted)

Question 43

Hallmark sign of homozygous FH?

Answer 43

orange-yellow xanthomas over knees, wrists, and interdigital webs (deposits fo LDL cholesterol that build up in macrophages of skin)

Question 44

What is the largest lipoprotein particle?

Answer 44

chylomicrons | float in centrifugation of blood = white, milky appearance in serum

Question 45

Which particle is mostly lipid and very little protein?

Answer 45

chylomicrons

Question 46

What is the smallest lipoprotein particle?

Answer 46

HDL

Question 47

Which particle is 50/50 protein/lipid?

Answer 47

HDL

Question 48

Describe the structure of a lipoprotein

Answer 48

- apolipoprotein wraps around surface monolayer of phospholipids and free cholesterol - hydroPHOBIC core of triglyceride and cholesterol esters

Question 49

Which lipoproteins are the most dense and smallest?

Answer 49

HDL | anti-atherogenic lipoproteins

Question 50

Which lipoproteins cause plaques to form and contribute to coronary artery disease?

Answer 50

LDL, IDL, VLDL (PRO-atherogenic lipoproteins) -least dense and largest

Question 51

When does atherosclerosis occur?

Answer 51

plaques of cholesterol laid down in arteries and eventually occlude artery = lack of blood supply to heart = heart attack

Question 52

Progression of atherosclerosis: initial lesion

Answer 52

macrophage infiltration --> foam cells

Question 53

drugs that block hepatic synthesis of cholesterol, but do not block intestinal uptake

Answer 53

statins

Question 54

drugs that bind to bile and prevent intestinal uptake

Answer 54

bile acid resins

Question 55

drugs that reduce intestinal uptake

Answer 55

soluble fiber

Question 56

drug that requires high doses and may have serious side effects, can be used in patients who do not tolerate statins

Answer 56

niacin (vit B3)

Question 57

drug that blocks intestinal absorption by blocking the NPC1L1 protein; most often used in combo with a statin

Answer 57

ezetimibe

Question 58

Required functions of cholesterol in. The body:

Answer 58

- Major component of the myelin sheath surrounding axons and necessary for nerve transmission - Provides the chemical backbone for synthesis of all steroid hormones like estrogens, vitamin D3, testosterone, progesterone, cortisol - Provides the chemical backbone for synthesis of bile acids which are needed to emulsify fats in the bile. - Component of lipid rafts and necessary for proper functioning of “coated pits” during endocytosis process

Question 59

In cholesterol uptake in the gut, sterols are released from micelles and transported into cell via _____ transporter.

Answer 59

NPC1L1

Question 60

In cholesterol uptake in the gut, once sterols have enter the enterocyte via the NPC1L1 transporter, the bulk of non-cholesterol sterols efflux back into the lumen via _____ transporters.

Answer 60

ABC

Question 61

In cholesterol uptake in the gut, esterified cholesterol and sterols enter the _____ system via _______.

Answer 61

Lymphatic | Chylomicrons

Question 62

Clinical importance of ABC transporters:

Answer 62

- Cause of drug resistance which develops in many human cancers. - Mutation in ABC chloride carrier is cause of cystic fibrosis. - Cause of drug resistance, which frequently develops in malaria Parasite. - export of cholesterol out of enterocyte into lumen***

Question 63

Cholesterol from extrahepatic tissues gets picked up tot eventually form HDL particle that ends up back into liver for recycling.

Answer 63

Reverse cholesterol transport

Question 64

Individuals with FH have mutations in which receptor?

Answer 64

LDL

Question 65

WHICH PATHWAY INVOLVES TRANSPORT OF CHYLOMICRON REMNANTS INTO THE LIVER?

Answer 65

Exogenous