Cholesterol Biosynthesis and Transport Genetics Part 2

Question 1

sodium hexametaphosphate (calgon)

Answer 1

developed 70+ years ago to prevent calcium deposits in pipes
prevented mineralization in plumbing

Question 2

dietary lipids (fat) have low —

Answer 2

solubility

Question 3

bile salts act as the — to emulsify dietary lipids

Answer 3

detergent

Question 4

— is the precursor of bile salts

Answer 4

cholesterol

Question 5

enterohepatic circulation

Answer 5

bile salts are reabsorbed in the GI tract for re-circulation back into the liver

Question 6

a significant amount of bile salts are excreted in — every day

Answer 6

feces

Question 7

bile salt excretion is the major way — is eliminated from the body

Answer 7

cholesterol

Question 8

how are bile salts amphipathic?

Answer 8

hydrophilic: hydroxyl groups, amino acid conjugate
hydrophobic: cholesterol derived portion with methyl groups

Question 9

what are the two functions of bile salts?

Answer 9

emulsification of lipid aggregates

solubilization and transport of lipids in aqueous environment

Question 10

emulsification of lipid aggregates

Answer 10

bile acids have detergent action on particles of dietary fat which causes fat globules to break down or be emulsified into minute, microscopic droplets. emulsification is not digestion per se, but is of importance because it greatly increases the surface area of fat, making it available for digestion by lipases, which cannot access the inside of lipid droplet s

Question 11

solubilization and transport of lipids in aqueous environment

Answer 11

bile acids are lipid carrier and are able to solubilize many lipids by forming micelles

Question 12

micelles are

Answer 12

aggregates of lipids such as fatty acids, cholesterol and monoglycerides that remain suspended in water

Question 13

most foods that are high in cholesterol are also high in

Answer 13

saturated fatty acids

Question 14

the current literature does not support an increased risk of cardiovascular disease and dietary cholesterol intake in healthy individuals, but foods high in saturated fatty acids and trans-fats do increase

Answer 14

cardiovascular disease risk

Question 15

which foods can help to lower cholesterol?

Answer 15

oats
barley
whole grains
beans
eggplant and okra
nuts
vegetable oils 
soy 
fatty fish
fiber supplements

Question 16

soluble fiber is critical for

Answer 16

cholesterol intake

Question 17

insoluble fiber is

Answer 17

regulatory (feces)

Question 18

cholesterol is a major component of the — — surrounding axons

Answer 18

myelin sheath

Question 19

cholesterol provides the chemical backbone for synthesis of all

Answer 19

steroid hormones

Question 20

cholesterol provides the chemical backbone for synthesis of — —

Answer 20

bile acids

Question 21

cholesterol is a component of — — and necessary for proper functioning of — — during endocytosis

Answer 21

lipid rafts

coated pits

Question 22

SREBP 1 and 2 transcription facts controlling fatty acid and cholesterol de novo synthesis are themselves

Answer 22

circadian core proteins on a 24 hour cycle

Question 23

cholesterol synthesis is — at night

Answer 23

high

Question 24

ideal cholesterol
total
LDL
HDL

Answer 24

<170
<110
>45

Question 25

high cholesterol is common in

Answer 25

older adults

Question 26

risk factors for high cholesterol which are out of our control

Answer 26

age (as people age their bodies tend to produce more cholesterol) genes ( a family history of high cholesterol or heart disease increases a persons risk of developing high cholesterol)

Question 27

risk factors of high cholesterol that can be controlled include (4)

Answer 27

smoking being overweight eating a poor diet living a sedentary life

Question 28

cholesterol in the digestive system exists as either --- --- or ---

Answer 28

bile salts | cholesterol

Question 29

bile salts are produced in the ---, stored in the ---, and secreted into the --- after eating

Answer 29

liver gallbladder duodenum

Question 30

bile salts are amphipathic molecules that act as a surfactant to emulsify lipids in food and form micelles containing (3)

Answer 30

monoglycerides phospholipids cholesterol

Question 31

--- brings cholesterol across the membrane

Answer 31

NPC1L1

Question 32

ABC transporters export cholesterol out of --- and into the ---

Answer 32

enterocyte | lumen

Question 33

major lipoproteins (5)

Answer 33

``` chylomicrons VLDL intermediate density lipoprotein LDL HDL ```

Question 34

chylomicrons carry

Answer 34

dietary lipid, large particles

Question 35

VLDL carry

Answer 35

endogenous triglyceride and some cholesterol

Question 36

IDL carry

Answer 36

cholesterol esters and triglycerides

Question 37

LDL carry

Answer 37

cholesterol esters

Question 38

HDL carry

Answer 38

cholesterol esters

Question 39

exogenous pathway

Answer 39

movement of cholesterol and fatty acid from the GI tract to chylomicrons to the liver

Question 40

reverse cholesterol transport

Answer 40

forming the different types of HCK that exists

Question 41

high levels of chylomicrons circulating can lead to

Answer 41

atherosclerosis

Question 42

exogenous pathway summary

Answer 42

1. dietary cholesterol and fatty acids are absorbed 2. triglycerides are formed in the intestinal cell from free fatty acids and glycerol and cholesterol is esterfied 3. triglycerides and cholesterol combine to form chylomicrons 4. chylomicrons enter the circulation and travel to peripheral sites 5. in peripheral tissues, free fatty acids are released from the chylomicrons to be used as energy, converted to triglyceride or stored in adipose 6. remnants are used in the formation of HDL

Question 43

endogenous pathway summary

Answer 43

1. VLDL is formed in the liver from triglycerides and cholesterol esters 2. These can be hydrolyzed by lipoprotein lipase to form IDL or VLDL remnants 3. VLDL remnants are cleared from the circulation or incorporated into LDL 4. LDL particles contain a core of cholesterol esters and a smaller amount of triglyceride 5. LDL is internalized by hepatic and nonhepatic tissues 6. In the liver, LDL is converted into bile acids and secreted into the intestines 7. In non hepatic tissues, LDL is used in hormone production, cell membrane synthesis, or stored 8. LDL is also taken up by macrophages and other cells which can lead to excess accumulation and the formation of foam cells which are important in plaque formation.

Question 44

reverse cholesterol transport summary

Answer 44

Lipid-poor preβ-HDL particles, produced in the liver or the intestine, initiate the efflux of cholesterol and phospholipids from cell membranes via interaction with the ATP-transporter A1 (ABCA1). Subsequent action of the lecithin-cholesterol acyl transferase (LCAT) esterifies cholesterol in preβ-HDL particles and converts them to mature α-HDL particles. Mature HDL can deliver cholesterol to the liver by one of two pathways: -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. The uptake of apoB-rich particles occurs via hepatic LDL Receptors (approximately 50% of RCT). The lypolysis of TG in TG-rich HDL by hepatic lipase and endothelial lipase leads to a smaller HDL which re-enters the RCT cycle.

Question 45

family history + high LDL cholesterol =

Answer 45

familial hypercholesterolemia (FHC)

Question 46

HDL | % lipid, % protein

Answer 46

50, 50

Question 47

chylomicrons | % lipid, % protein

Answer 47

99, 1

Question 48

the cytoplasmic tail of the LDL receptor has a specific sequence of aa which internalize the

Answer 48

receptor once LDL has bound

Question 49

mutations in the internalization signal prevents

Answer 49

internalization, so it accumulates and you dont have the negative feedback to prevent cholesterol synthesis

Question 50

lipoprotein structure

Answer 50

surface monolayer of phospholipids and free cholesterol hydrophobic core of triglyceride and cholesteryl esters

Question 51

--- are wrapped around lipoproteins

Answer 51

apolipoprotein

Question 52

size order of lipoprotein, large to small

Answer 52

``` chylomicrons chylomicron remnants VLDL IDL LDL HDL ```

Question 53

what do statins block?

Answer 53

hepatic synthesis of cholesterol, but do not block intestinal uptake

Question 54

bile acid resins bind to bile and prevent

Answer 54

intestinal uptake

Question 55

soluble fiber reduces

Answer 55

intestinal uptake

Question 56

niacin (vitamin b3) reuires high doses and may have serious side effects, can be used in patients who do not tolerate

Answer 56

statins

Question 57

exetimibe blocks

Answer 57

intestinal absorption by blocking the NPC1L1 protein. most often combined with a statin. vytorin is a combo of simvastatin and ezetimibe in a single pill