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Biochemistry > Cholesterol Biosynthesis, Transport and Genetics 2 > Flashcards

Cholesterol Biosynthesis, Transport and Genetics 2 Flashcards

1
Q

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

A

saturated fatty acids

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2
Q

Which foods increase cardiovascular disease risk?

A

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

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3
Q

What is the best dietary way to lower cholesterol?

A

eat more FIBER

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4
Q

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

A

soluble fiber

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5
Q

Why is soluble fiber important?

A

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

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6
Q

Where does cholesterol in the body come from?

A

diet

synthesis by the body (liver and intestine)

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7
Q

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

A

age

genes

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8
Q

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

A

as they AGE

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9
Q

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

A

true

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10
Q

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

A

smoking
overweight
poor diet
sedentary lifestyle

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11
Q

How does nicotine affect cholesterol?

A

lowers good cholesterol (HDL)

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12
Q

How does cholesterol exist in the gut?

A

bile salts

cholesterol

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13
Q

Where are bile salts produced, stored and secreted into?

A

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

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14
Q

What types of molecules are bile salts?

A

amphipathic

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15
Q

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

A

bile salts

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16
Q

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

A

NPC1L1

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17
Q

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

A

ABCG5/G8

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18
Q

What are the 5 major lipoproteins?

A
  • chylomicrons
  • VLDL
  • IDL
  • LDL
  • HDL
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19
Q

large particles that carry dietary lipid

A

chylomicrons

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20
Q

carry endogenous triglyceride and some cholesterol

A

VLDL

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21
Q

carry cholesterol esters and triglycerides

A

IDL

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22
Q

carry cholesterol esters

A

LDL

HDL

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23
Q

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

A

exogenous

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24
Q

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

A

endogenous

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25
Q

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

A

reverse cholesterol transport

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26
Q

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

A

exogenous

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27
Q

Which lipoproteins are involved in the ENDOgenous pathway?

A

VLDL and LDL

28
Q

In the endogenous pathway, where is VLDL formed?

A

liver from triglycerides and cholesterol esters

29
Q

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

A

IDL or VLDL remnants

30
Q

Where do VLDL remnants go?

A

cleared from the circulation or incorporated into LDL

31
Q

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

A

cholesterol esters

triglyceride

32
Q

What is LDL internalized by?

A

hepatic and nonhepatic tissues

33
Q

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

A

bile salts

intestines

34
Q

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

A

hormone production
cell membrane synthesis
stored

35
Q

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.

A

macrophages

foam cells

36
Q

Which cells are important in plaque formation

A

foam cells

37
Q

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

A

Lipid-poor preβ-HDL

ATP-transporter A1 (ABCA1).

38
Q

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

A

lecithin-cholesterol acyl transferase (LCAT)

39
Q

How can mature HDL deliver cholesterol to the liver?

A
  • 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.

40
Q

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

A

hepatic LDL Receptors

41
Q

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

A

lypolysis

42
Q

includes family history and HIGH LDL cholesterol

A

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

43
Q

Hallmark sign of homozygous FH?

A

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

44
Q

What is the largest lipoprotein particle?

A

chylomicrons

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

45
Q

Which particle is mostly lipid and very little protein?

A

chylomicrons

46
Q

What is the smallest lipoprotein particle?

A

HDL

47
Q

Which particle is 50/50 protein/lipid?

A

HDL

48
Q

Describe the structure of a lipoprotein

A
  • apolipoprotein wraps around surface monolayer of phospholipids and free cholesterol
  • hydroPHOBIC core of triglyceride and cholesterol esters
49
Q

Which lipoproteins are the most dense and smallest?

A

HDL

anti-atherogenic lipoproteins

50
Q

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

A

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

51
Q

When does atherosclerosis occur?

A

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

52
Q

Progression of atherosclerosis: initial lesion

A

macrophage infiltration –> foam cells

53
Q

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

A

statins

54
Q

drugs that bind to bile and prevent intestinal uptake

A

bile acid resins

55
Q

drugs that reduce intestinal uptake

A

soluble fiber

56
Q

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

A

niacin (vit B3)

57
Q

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

A

ezetimibe

58
Q

Required functions of cholesterol in. The body:

A
  • 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
59
Q

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

A

NPC1L1

60
Q

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.

A

ABC

61
Q

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

A

Lymphatic

Chylomicrons

62
Q

Clinical importance of ABC transporters:

A
  • 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***
63
Q

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

A

Reverse cholesterol transport

64
Q

Individuals with FH have mutations in which receptor?

A

LDL

65
Q

WHICH PATHWAY INVOLVES TRANSPORT OF CHYLOMICRON REMNANTS INTO THE LIVER?

A

Exogenous

Biochemistry (9 decks)

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