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Applied Biochemistry > Cholesterol Biosynthesis and Transport Genetics Part 2 > Flashcards

Cholesterol Biosynthesis and Transport Genetics Part 2 Flashcards

1
Q

sodium hexametaphosphate (calgon)

A

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

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2
Q

dietary lipids (fat) have low —

A

solubility

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3
Q

bile salts act as the — to emulsify dietary lipids

A

detergent

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4
Q

— is the precursor of bile salts

A

cholesterol

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5
Q

enterohepatic circulation

A

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

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6
Q

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

A

feces

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7
Q

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

A

cholesterol

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8
Q

how are bile salts amphipathic?

A

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

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9
Q

what are the two functions of bile salts?

A

emulsification of lipid aggregates

solubilization and transport of lipids in aqueous environment

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10
Q

emulsification of lipid aggregates

A

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

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11
Q

solubilization and transport of lipids in aqueous environment

A

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

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12
Q

micelles are

A

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

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13
Q

most foods that are high in cholesterol are also high in

A

saturated fatty acids

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14
Q

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

A

cardiovascular disease risk

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15
Q

which foods can help to lower cholesterol?

A 
oats
barley
whole grains
beans
eggplant and okra
nuts
vegetable oils 
soy 
fatty fish
fiber supplements
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16
Q

soluble fiber is critical for

A

cholesterol intake

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17
Q

insoluble fiber is

A

regulatory (feces)

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18
Q

cholesterol is a major component of the — — surrounding axons

A

myelin sheath

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19
Q

cholesterol provides the chemical backbone for synthesis of all

A

steroid hormones

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20
Q

cholesterol provides the chemical backbone for synthesis of — —

A

bile acids

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21
Q

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

A

lipid rafts

coated pits

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22
Q

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

A

circadian core proteins on a 24 hour cycle

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23
Q

cholesterol synthesis is — at night

A

high

24
Q

ideal cholesterol
total
LDL
HDL

A

<170
<110
>45

25
Q

high cholesterol is common in

A

older adults

26
Q

risk factors for high cholesterol which are out of our control

A

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)

27
Q

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

A

smoking
being overweight
eating a poor diet
living a sedentary life

28
Q

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

A

bile salts

cholesterol

29
Q

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

A

liver
gallbladder
duodenum

30
Q

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

A

monoglycerides
phospholipids
cholesterol

31
Q

— brings cholesterol across the membrane

A

NPC1L1

32
Q

ABC transporters export cholesterol out of — and into the —

A

enterocyte

lumen

33
Q

major lipoproteins (5)

A 
chylomicrons 
VLDL
intermediate density lipoprotein
LDL
HDL
34
Q

chylomicrons carry

A

dietary lipid, large particles

35
Q

VLDL carry

A

endogenous triglyceride and some cholesterol

36
Q

IDL carry

A

cholesterol esters and triglycerides

37
Q

LDL carry

A

cholesterol esters

38
Q

HDL carry

A

cholesterol esters

39
Q

exogenous pathway

A

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

40
Q

reverse cholesterol transport

A

forming the different types of HCK that exists

41
Q

high levels of chylomicrons circulating can lead to

A

atherosclerosis

42
Q

exogenous pathway summary

A
  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
43
Q

endogenous pathway summary

A
  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.
44
Q

reverse cholesterol transport summary

A

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.

45
Q

family history + high LDL cholesterol =

A

familial hypercholesterolemia (FHC)

46
Q

HDL

% lipid, % protein

A

50, 50

47
Q

chylomicrons

% lipid, % protein

A

99, 1

48
Q

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

A

receptor once LDL has bound

49
Q

mutations in the internalization signal prevents

A

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

50
Q

lipoprotein structure

A

surface monolayer of phospholipids and free cholesterol

hydrophobic core of triglyceride and cholesteryl esters

51
Q

— are wrapped around lipoproteins

A

apolipoprotein

52
Q

size order of lipoprotein, large to small

A 
chylomicrons 
chylomicron remnants 
VLDL
IDL
LDL
HDL
53
Q

what do statins block?

A

hepatic synthesis of cholesterol, but do not block intestinal uptake

54
Q

bile acid resins bind to bile and prevent

A

intestinal uptake

55
Q

soluble fiber reduces

A

intestinal uptake

56
Q

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

A

statins

57
Q

exetimibe blocks

A

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

Applied Biochemistry (52 decks)

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