Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Cardio > Biochem of Lipids and Lipoproteins > Flashcards

Biochem of Lipids and Lipoproteins Flashcards

1
Q 
Triglycerides
function
structure
elevation predicts what
>1000 mg/dL predicts what?
A

functions to store fats
glycerol OH, and the OHs are replaced by fatty acids
elevation is a independent predictor of increased CVD risk
-if more than 1000mg/dl—>increased risk for pancreatitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Cholesterol
5 functions
3 major products that are synthesized from cholesterol. what are their precursors?

A

membrane (decrease fluidity)
signal transduction
covalent modification in embryonic signalling
bile acids
steroid hormones
-vitamin D (7alpha dehydroxycholesterol), bile acids (7alpha hydroxycholesterol), androgens/estrogens/glucocorticoids/mineralocorticoids (Pregnenolone)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

4 major steps of cholesterol synthesis

what is the rate limiting step

A
  1. Acetyl CoA x2 is made to HMGCoA then to mevalonate
  2. mevalonate is phosphorylated x3 and decarboxylated to isoprenes (activated)
  3. 6 isoprene condense to form squalene, which is linear
  4. the squalene cyclizes to form choesterol.

Rate limiting step is HMGCoA to mevalonate via enzyme “HMGCoA Reductase”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Where is cholesterol synthesized?

What happens to it post synthesis

A

It is synthesized in the liver, and then transported to other tissues (as bile, biliary cholesterols, and cholesterol esters in lipoproteins) to be converted to the various hormones.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What does emulsifying mean?

A

to increase the surface area of the fat to lipase attack

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Where are two locations that produce hormones from cholesterol?
What are the hormones they produce?

A

Adrenal Gland: mineralcorticoids, glucocorticoids

Gonads: estrogen, androgens, progesterone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is Cholesterol Ester. Structure?
How is it synthesized?
What is special about it compared to cholesterol?

A

It is the storage form of cholesterol in lipoproteins. It is synthesized via ACAT with addition of a fatty acid group in place of the OH
It is more hydrophobic than cholesterol therefore must be carried on lipoproteins to be stored in liver.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

List the lipoproteins according to size

A

chylomicrons, VLDL, LDL/Lpa, HDL

larger ones have more TG and less apoprotein, smaller ones have more apoproteins and less TG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Lipoprotein
what’s in the outer layer
what’s in the core?

A

Core: TG and CE

outer layer: phospholipids (monolayer) and apolipoproteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q 
Apolipoproteins for
Chylomicrons
VLDL
LDL
HDL
A

chylomicrons: ApoB48
VLDL: ApoB100
LDL: ApoB100
HDL: ApoAI/ApoAII

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Functions of Apolpoproteins (3)

A

solubilize lipoproteins in circulation
activate/inactivate plasma enzymes
serve as ligand for cell receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Which lipoproteins are involved in atherosclerosis? (3)

A

VLDL, IDL, and LDL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

General overview of Extrinsic TG and Cholesterol pathway

A

Fats are emulsified by bile and taken up by NPC1L1 into epithelium where it is broken down to TG then packaged into chylomicrons. Chylomicrons then circulate the blood until broken down to smaller lipoproteins by LPL either for storage or for oxidation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q 
NPC1L1
what does it standfor?
Where is it located?
What does it do?
What is a drug that targets this?
A

Niemann Pick C1 like 1 protein. Located on luminal surface of epithelium.responsible for absorption of sterols from diet.
This can be inhibited by Ezetimide… thereby decreasing intake of sterols via diet.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

ABCG5/ABCG8
Where is it located?
What does it do?
Why does it have to do this?

A

ABCG5/8 are responsible for exportation of plant sterols from the intestinal epithelium. This is because plant sterols are NOT esterified and cannot be incolporated into the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Sitosterolemia

  • what is dysfunctional
  • what does this lead to?
  • what are the symptoms and what is clinically significant about this?
A

Dysfunction of ABCG5/8 therefore cannot transport out the plant steroids.
Therefore, accumulation of sterols in tendons and subQ–>Xanthomas and increased risk for premature CVD.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What do chylomicrons carry internally
where do they get their apoproteins from?
What are the apolipoproteins?
Where is everything from?

A

Internally Chylomicrons carry sterols and TG.
Apolipoproteins are either synthesized by epithelial cells OR they are from HDL
Epith cell: ApoB48, ApoA1, ApoAIV
HDL: CII, CIII, and ApoE

THE DIET

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what three things are chylomicrons important for absorption?

A
  • TG (lipids)
  • sterols
  • fat soluble vitamins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

how much of chylomicrons is fat?

What is the TG to cholesterol ratio?

A

98-99% fat

10:1 TG to cholesterol ratio

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Post meal how soon do chylos show up?

Post fast, how long do chylomicrons last?

A

3-6 hours will see chylos

10-12 hours post fast, they will be gone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

ApoB48
synthesized in what?
On what lipoprotein?

A

ONLY synthesized by epithelials of small intestines

ONLYon chylos

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

LPL
Where are they located?
What do they interact with? Which kind of lipoproteins do they interact with?
What turns it on what turns it off?
What is a cofactor?
What happens to the rest of the particle?
Name a disease of LPL deficiency?

A

located on endothelial cells of skeletal/cardiac muscle and adipose/mammary tissue
-They interact with Chylos and VLDL. Specifically interacting with CII and CIII (which turns it on and off)
HEPARIN
The rest of the particle is shrunken and will be “chylo remnmants” and are taken to the liver.
deficiency is lethal.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

LPL regulation:
What happens with blood sugar is elevated?
What happens when blood sugar is low?
Which situation is ketoacidosis?

A

When glucose is up–>insulin is up. Therefore “store”… so LPL is transcriptionally upregulated
When glucose is down… Do not store… therefore LPL is transcriptionally down regulated
Ketoacidosis is glucose down.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How do you measure LPL?

A

Heparin can be administered IV to pull LPL to the blood for measuring

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What happens to the chylomicron remnant?

A

Taken to the liver. –Cholesterol is dropped off to be processed to bile/VLDL
–ApoE binds LDLR or LRP to be endocytosed at the liver.
(ApoB48 is degraded so ApoE becomes more and more)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

If you see chylomicrons in the blood over 12 hours what do you suspect?

A

Problem with chylomicron metabolism. Possibly Deficiency in ApoE—leading to type III hyperlipoproteinemia.)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q 
LRP
what is it 
what does it do?
what is it similar to?
what does it bind?
A

LDL R related protein

binds apoE and takes up VLDL and chylomicrons just as LDLR does. LRP is LDLR backup.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

VLDL
synthesized where?
under what circumstances is it increased?
What is it’s goal?
Apoproteins? Where are these apoproteins synthesized?

A

syth occurs in the liver when there’s 1. increased fatty acid intake (dropped off in the liver by chylomicrons partly) and 2. when there’s an increased denovo synthesis.
package FAs and cholesterol to be transported from liver to peripheral tissue
ApoB100, CI, CII, CIII, ApoE (ALL SYNTHESIZED IN LIVER

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Other than straight up fats. what else is converted to VLDL?

A

excessive dietary sugars (stored in liver already)

30
Q

microsomal triglyceride transfer protein (MTP)

What does it do?

A

transfers TG to chylomicrons in the epithelium and transfers TG to VLDL in liver.

31
Q

abetalipoproteinemia
what is dysfunctional?
what are symptoms?

A

MTP is dysfunctional. Therefore anything with a Beta apolipoprotein will be dysfunctional.
Chylomicrons and VLDL cannot accumulate TGs
Therefore… fatty stool. lack of fat soluble vitamins. developmental delays

32
Q

VLDL is made where? organ? organelle?

A

organ is liver

organelle is ER

33
Q

ACAT1 vs. ACAT2
what do they do
where are they

A

ACAT 1 is extrahepatic tissues such as macrophages/foam cells–> leads to extrahepatic Cholesterol conversion to cholesterol ester

ACAT2 is in the liver and in intestinal epithelium. This is important for cholesterol uptake and conversion to CE for transport.

34
Q

VLDL transport and action?
Fates of VLDL remnants? (2)
T1/2 of VLDL remnants?

A

VLDL transports cholesterol and TGs through blood to. CII binds LPL (with Heparin) and TG are released to adipose for storage and muscle for oxidation.

IDL=VLDL remnants–> released to blood.

  1. The VLDL remnants are either endocytosed by the liver by LDLR or LRP via binding to ApoE or ApoB100
  2. It can be converted to LDL by HL also by ApoE binding
35
Q

Where do LDLs come from?
Where is it synthesized?
by what enzyme?

A

LDLs are ALL made from VLDL. from HL by binding apoE in the liver… (where as some VLDLs are endocytosed by the liver)

36
Q

When VLDL is converted to LDL… what happens to the apoC and apoE?

What is the biggest difference btween VLDL and LDL?

A

When VLDL is converted to LDL ApoE and apoC fall off and are transferred to HDL.

VLDL loses about 70% of its TGs when it’s converted to LDL…therefore it contains much more cholesterol and cholesterol ester

37
Q

LDL
major apolipoprotein
what determines its production?
What happens to the LDL? What binds LDLR?

A

apoB100
production is determined by VLDL removal/metabolism
-LDLR binds apoB100

38
Q

What is the BEST way to lower LDL? theoretically

A

increasing LDLR transcriptional activity.

39
Q

What is LDL’s function

A

LDL transports CHOLESTEROL to myocytes and adipose tissue. It is taken up by ApoB100-LDLR on endothelium

40
Q

Lipoprotein T1/2
chylomicron
VLDL
LDL

A

chylomicron-5-20 minutes
VLDL-30 minutes to 1 hours
LDL-2.5 days

41
Q

at what site is 75% of LDL removed?

A

Liver LDLR

42
Q

Receptor mediated endocytosis process of LDL

A

LDLR binds ApoB100 and endosome fuses with lysosome. The receptors are recycled and the rest are degraded to fats, cholesterols, and AAs.

43
Q

Hypercholesterolemia

  • most common cause
  • mode of inheretance
  • what are other forms of mutations of hypercholesterolemia? and what are the modes of inheritance?
A

most common cause is mutations in LDLR. Autosomal dominant.

Could also be due to binding regions of ApoB100, which binds to LDLR. These are also autosomal dominant
Could be due to PCSK9 GOF

44
Q

Manipulation (lowering) of LDL-C levels
Most effective way
other ways (4)

A 
LDLR decrease in gene expression
4 ways to achieve this: 
-pharmacologic
-dietary/lifestyle
-estrogen
-thyroxine
45
Q

LDL transcriptional regulation and feedback mechanism

A

SREBP is normally bound to SCAP on ER membrane. When sterol levels increase, it will bind and stablize this complex. when sterol level falls. Scap will be cleaved, and SREBP transmembrane domain will be cleaved. SREBP will be released to increase transcription of HMG CoA reductase AND LDLR

46
Q

When sterols are high… what are the three consequences

A
  1. HMG CoA reductase transcription decreases
  2. LDLR transcription decreases
  3. increase in ACAT therefore CE stored form of cholesterol.
47
Q

PCSK9
what kind of protein is it?
Where is it located? Organ? microscopically?
What does it do?

A

It is a serine protease
Located on hepatocytes. On LDLR
It signals LDLR-PCSK9 complexes to be endocytosed and degraded. regulates LDLR numbers

48
Q

PCSK9 GOF mutation? action? disease/mode of inheritance?

LOF mutation?

A

GOF means less LDLR. could lead to hypercholesterolemia.
It is autosomal dominant (other causes can be LDLR mutation, apoB100 mutation)
LOF means increase in LDLR

49
Q 
LP(a) is a risk factor for what?
Where is it made?
What is it's structure?
Increased LP(a) size correlates to what?
T1/2 of LP (a)
A

cardiovascular disease
It is made in hepatocytes, and it is a LDL’s ApoB100 covalently attached to an apoa protein. Apoprotein a has Kringle sites, so that the larger the LPa is, the smaller amount there is in the blood.

50
Q

Actions of HDL (7)

A 
antioxidant
pro-endothelial function:
-anti adhesion
-anti thrombosis
-anti inflammatory
-proendothelial healing
stablizes plaque
51
Q

What is the MAIN physiological function of HDL in cholesterol transport?
apolipoproteins

A

functions to transport cholesterol from peripheral tissue back to liver for bile synthesis

  • apoA1
  • apoAII
  • C apolipoproteins (CII,CIII)… which are transferred to VLDL and chylomicrons
  • LCAT-lecithincholesterol acy transferase.
52
Q 
ApoA1
what function does it have?
where is it synthesized
what is it necessary for?
over expression vs under expression
A

ApoA1 is needed to activate LCAT
it is synthesized in the liver and intestinal epithelium
It’s necessary for HDL synthesis
overexpression means increased HDL and protection from atherosclerosis
underexpression means no LCAT function

53
Q

ABCA1
where is this located? organs?
action?
what lipoprotein does it work with?

A

ABCA1 is located on plasma membrane of cells of the intestines, macrophages, brain… extrahepatic cells.
Cholesterol and phospholipids efflux through ABCA1 and bind to apoA1 that is on discoid HDLs
This is the process of making HDLs

54
Q 
Tangier Disease
What mutation?
what is the effect?
What abnormal lab values?
symptoms
A

Tangier disease has mutation of ABCA1, which is the efflux channel for cholesterol and phospholipids to flow to apoA1 of HDL from extrahepatic tissues

  • This results in almost NO HDL of any form
  • REsults in LOW HDL and VERY LOW TOtal Cholesterol in blood
  • swollen spleen and lymph nodes and tonsils. Orange in color due to accumulation of carotenoids.
55
Q

HDL synthesis
what are prebetaHDL
what are 2 ways that prebeta HDL come about?

A

prebetaHDL are the outer layers of HDL with out the CE/triglyceride core. It is discoid

  1. This can be made in the intestines/liver
  2. it can also be made from VLDL and chylomicrons when they lose apoA1 and phoepholipds as they are hydrolized
56
Q

LCAT
what does it do? (from what tissue to what tissue?)
what activates it?

A

LCAT esterifies cholesterol in extrahepatic tissues, so that it can be transferred to HDL for carriage back to liver.
-ApoA1 activates it.

57
Q

ABCG1

  • function
  • what does it contribute to? what does this change?
A

to efflux cholesterols out of exrahepatic cells to HDL (not discoid HDL)
HDL remodeling–thereby changing metabolism, function, and concentration of HDL

58
Q

What happens once the HDL is fully made?

A

The fully functioning HDL gives CE to VLDL and LDL through CETP. In return it gets TG.

The newly accquired CE in VLDL and LDL then are carried to liver via mechanisms described before. (LDLR mediated endocytosis)

59
Q

CETP deficiency effects?

A

decreasing CETP function leads to less transfer of cholesterols from HDL to LDL and VLDL. Therefore there’s an increased in HDL

60
Q

PLTP

function?

A

promotes efflux of cholesterolesters (from ABCG1) (along with apoA1)

61
Q

what are needed for max LCAT function?

A

ApoA1 for activation and PLTP

62
Q

What is the major acceptor of cellular cholesterol?

A

prebetaHDL

63
Q 
Hepatic Lipase
function
What are somethings that modify its function?
A

It hydrolyzes triglycerides and phospholipids of spherical HDL to generate smaller molecules to circulate and gather more cholesterols.

  • this occurs AFTER remodeling by CETP and PLTP
  • estrogen reduces HL activity increases HDL-C slightly.
  • androgen increases HL activity. effect is significant therefore men have lower HDL-C values

HL IS MAJOR HDL REGULATOR

64
Q 
endothelial Lipase (EL)
function
which lipoprotein does it interact with?
over expression vs null mutation?
What is something that inhibits EL activity?
A

generates smaller HDL particles… so can be catabolized faster.

  • reduces HDL affinity to SRBI
  • over production reduces HDL to amost none
  • null mice are protected against atherosclerosis
  • ApoAII inhibits EL activity—therefore resulting in higher levels of HDL
65
Q

What is the function of ApoAII

A

ApoAII inhibits EL, so that HDL remains big and thereby is atheroprotective

66
Q 
SR-BI
what is it?
specifically what does it do?
which organs have this?
Overexpression vs. underexpression
A

Scavenger receptor B1 is an HDL receptor.
-it transfers ONLY THE LIPID from HDL to the cells of the liver, ovaries, testes, and adrenal gland (NOT THE ENTIRE PARTICLE)–the particle w/o lipids can circulate back to pick up more cholesterol.
-in liver, ovaries, tests, adrenal glands
Overexpression decreases HDL-cholesterol and increases uptake by these organs
Underexpression increases HDL levels in blood and decrease lipids in liver, ovaries, testes, and adrenal glands

-Therefore SRBI is atheroprotective
by delivering sterols to organs for steroidogenesis

67
Q

Enterohepatic circulation

A

liver cholesterols are secreted to gall bladder as bile or conjugated bile acids (7alpha hydroxylase)
-bile is reabosrbed and returns to liver via portal vein and resecreted.
small amounts are lost in stool.

68
Q

name three main regulators of cholesterol syntehsis and transport

A
  1. HMGcoA reductase transc
  2. ACAT activation
  3. LDLR transcription
69
Q

HMG coa Reductase regulation

Short term

A

AMP dependent. HMGCoa reductase is phosphorylated when AMP is high. Therefore when Glucagon and epinephrine is high (AMP is high) HMGcoa reductase is inhibited.

It is activated when ATP is high so AMP is low…. AKA when insulin is high HMGCoA reductase is dephosphorylated

This is covalent modification

70
Q

name short and long term methods of cholesterol regulation

A

short: covalent mod via AMP/phosphorylation
long: sterol level autoregulation of LDLR and HMGcoareductase transcription via SREBPand Scap

Cardio (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions