Biochemistry: Lipid Transport

Front 1

What are the five major components are where are they typically found?

Back 1

Apolipoprotein- both center and surface
Phospholipid- surface
Free cholesterol- surface
Cholesterolester- center
Triglyceride- center
*note that the composition is constantly changing.

Front 2

How many apolipoproteins have been identified?

Back 2

9

Front 3

What do apolipoprotiens do?

Back 3

Structural, receptor binding (endocytosis), lipase activation, lipid transfer

Regulate lipid metabolizing enzymes in blood, facilitate transfer of lipids between lipoprotein classes and between lipoprotein and cells, mediate endocytosis of lipoproteins by binding to cell surface receptors.

Front 4

What's the order of lipoproteins by increasing density?

Back 4

Chylomicorns, VLDL, LDL, HDL

Front 5

What's the order of lipoproteins by electrophoretic analysis?

Back 5

CATHODE (-)-- Chylomicrons, beta lipoproteins (LDL) prelipiproteins (VLDL), alpha lipiproteins (HDL)-- ANODE (+)

Front 6

What's the source and composition of serum chylomicrons?

Back 6

Source: Intestine
Protein: 2%
TG: 85%
PL: 8%
Cholesterol + cholesterol ester: 5%

Front 7

What's the source and composition of serum VLDL?

Back 7

Source: Liver
Protein: 10%
TG: 55%
PL: 18%
Cholesterol + cholesterol ester: 17%

Front 8

What's the source and composition of serum LDL?

Back 8

Source: VLDL
Protein: 22%
TG: 9%
PL: 20%
Cholesterol + cholesterol ester: 49%

Front 9

What's the source and competition of HDL?

Back 9

Source: Liver, intestine
Protein: 50%
TG: 4%
PL: 30%
Cholesterol + cholesterol ester: 16%

Front 10

What's the major role of chylomicrons?

Back 10

To transport TG from intestines to other tissues. Present only after a fatty meal.

Front 11

What's the major role of VLDL?

Back 11

Lipids synthesized by liver and relased as VLDL. It is a precursor of LDL.

Front 12

What is the origin of IDL particles?

Back 12

They're the smaller remanant proteins of VLDL that gets recycled to LDL. Requires hydrolysis of TG and PL by hepatic lipase.

Front 13

What's the origin and function of LDL particles?

Back 13

From VLDL, mostly carries cholesterol.

Front 14

Which lipoprotein is A1 associated with? What's the source? What's the function?

Back 14

Lipoprotein: HDL, chylomicrons
Source: Liver, intestine
Function: Activates lecithin-cholesterol acyltransferase in HDL

Front 15

Which lipoprotein is B-48 associated with? What's the source? What's the function?

Back 15

Lipoprotein: Chylomicrons
Source: Intestine
Function: Structural protein for chylomicrons

Front 16

Which lipoprotein is B-100 associated with? What's the source? What's the function?

Back 16

Lipoprotein: VLDL, LDL
Source: Liver
Function: Serves as a structural protein for VLDL and LDL, contains LDL receptor binding domain. Most of LDL ends up hydrolyzed by the liver, but in extrahepatic tissues, LDL receptor is the major external source of cholesterol.

Front 17

Which lipoprotein is C-II associated with? What's the source? What's the function?

Back 17

Lipoprotein: HDL, VLDL, chylomicrons
Source: Liver
Function: Activates extrahepatic lipoprotein lipase

Front 18

Which lipoprotein is E associated with? What's the source? What's the function?

Back 18

Lipoprotein: VLDL, chylomicrons
Source: Liver
Function: Mediates uptake of chylomicron remnants by the liver

Front 19

What function does ApoB100 have that ApoB48 does not have?

Back 19

Receptor mediated endocytosis by extrahepatic tissues

Front 20

How does the extra function of ApoB100 correlate with its role in delivering cholesterol to the tissues?

Back 20

Some goes to the liver, and some goes to other tissues.

Front 21

How is ApoE carried from the liver?

Back 21

VLDL carries it from the liver and it goes to HDL. HDL can then donate it back to VLDL or chylomicrons.

Front 22

Which lipoprotein receive the ApoE

Back 22

Chylomicrons and VLDL

Front 23

Which receptor binds to ApoE?

Back 23

ApoE receptor in liver

Front 24

What are the steps in the life cycle of chylomicrons?

Back 24

They start in the intestines and contain mostly triglycerides They have B-48, AI and AII attached. They go through the lymph and then to the blood, where HDL adds ApoC and ApoE to them. Then, they go to capillaries of tissues, where LPL attached to herapan sulfate degrades some of its TG. More ApoE and cholesterol esters are added by HDL in exchange for some of it's current proteins and finally, the chylomicron remmant binds to ApoE receptor in the liver.

Front 25

Where does ApoC and ApoE come from in chylomicrons?

Back 25

They get added in the blood by HDL

Front 26

What are the major lipids transported by chylomicrons, VLDL, and LDL? Where do they go?

Back 26

Chylomicrons- TG, mostly to endothelial cells
VLDL- TG, mostly to endothelial cells, some to liver
LDL- TG, C, CE, PL, to be endocytosed by tissue cells.

Front 27

Where do the fatty acids that make up VLDL normally come from?

Back 27

Liver cell (ER and golgi)

Front 28

What is lecithin cholesterol acyl transferase (LCAT)?

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Back 28

Enzyme on HDL that is activated by ApoI, which combines cholesterol and phopshatidyl choline and turns it into cholesterol ester and 2-Lysophosphatidylcholine.

(Lysolecithin --> transferred to albumin --> HDL3)

Front 29

How is the acylCoA cholesterol acyl transferase (ACAT) enzyme different than LCAT?

Back 29

ACAT stores cholesterol as cholesterol esters in the liver.

Front 30

Where are ACAT and LCAT found?

Back 30

LCAT is found on HDL
ACAT is in the liver.

Front 31

What is the fate of the LDL receptor?

Back 31

It is endocytosed and then recycled back to the membrane.

Front 32

What determines the number of LDL receptors on the surface of the cells?

Back 32

The amount of cholesterol in the cell. Which depends on how fast ACAT is converting them into cholesterol esters, and how fast HMGCoA reductase is turning acetylCoA into cholesterol.

Front 33

What is the path of HDL?

Back 33

HDL starts from the liver and intestine with A1, in the blood, it gets ApoC, E, other lipoproteins, C, LCAT and CETP. Then, ApoA1 docs it onto peripheral tissue where C gets transfered in. some CE goes into remnants of chylomicrons and VLDL in exchange for more PL, TG, and C. Then, it picks up some more C from other peripheral tissues, and then it goes back to the liver where HL breaks some of its contents down, and SR-BI takes in some of the CE. Then it recirculates.

Front 34

What happens during HDL maturation?

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Back 34

It becomes a sphere (HDL3), Cholesterol gets converted to a cholesterol ester and phospholipidylcholine by LCAT, which then gets converted into lysolecithin by and transfered into the blood and carried by albumin.

Front 35

What kind of interchange occurs between HDL particles and VLDL and chylomicron particles?

Back 35

CE goes into the chylomicron via CETP and VLDL remnants, and C, TG, and PL gets transfered into the HDL3.

Front 36

What is the term for immature HDL? What is its shape?

Back 36

Nascent, disk

Front 37

What apoproteins are contained in HDL?

Back 37

From the liver: ApoAI, II, C, E
From the Intestine: ApoAI only

Front 38

What enzyme is contained in HDL particles?

Back 38

LCAT

Front 39

What functions do HDL particles have?

Back 39

They turn free cholesterol into cholesterol esters.

Front 40

What is type I hyperlipoproteinemia?

Back 40

Hyperchylomicronemia; TG elevated, lipoprotein lipase or ApoCII deficiency

Front 41

What is type II hyperliporpoteinemia?

Back 41

Hypercholesterolemia; LDL elevated, LDL receptor defiency or secondary causes (diabetes, obesity, hypothyroidism)

Heterozygote has 2X normal LDL, endogenous cholesterol synthesis stimulated.

Hymozygotes are removed from the gene pool before age 20

Xanthomas (subcutaneous yellow lipid deposits) are characteristic of patients.

Front 42

What is type III hyperlipoproteinemia?

Back 42

Dysbetalipoproteinemia; homozygous recessive ApoE2 (elevated remnants)