Uth Biochemistry Block Iii Lecture 8

Front 1

90% of dietary lipids are in the form of what?

Back 1

Triacylglycerol

Front 2

Mouth and Stomach produce what?

Back 2

Acid stable oral lipase and gastric lipase which work on short chain esters. Gastric lipase functions in infants due to neutral pH of stomach.

Front 3

The hormone cholecystokinin signals the release of what?

Back 3

Cholecystokinin signals the release of gallbladder bile.

Front 4

The hormone secretenin signals the release of what?

Back 4

Pancreatic contents

Front 5

Bile contains ___.

Back 5

Bile salts and phosphatidylcholine-- both are emulsifiers.

Front 6

Pancreas provides bicarbonate and several lipases including (name 3).

Back 6

Pancreatic lipase works with colipase, breaks down triacylglycerol into 2FA and 2-Monoacylglycerol

Cholesterol ester hydrolase

Phopholipase A2 (delivered as a proenzyme) plus lysophospholipase, breaks down phospholipid into FA and lysolipid (that can act as a detergent)

Front 7

Micelles are formed from ___. Incorporate what?

Back 7

Bile salts, lysophosphatidylcholine, and FA

Incorporate more hydrophobic cholesterol and vitamins

Front 8

Chylomicrons, VLDL, LDL, IDL, and HDL are all ___.

Back 8

Serum lipoproteins- macromolecular complexes of lipids and specialized lipid associating proteins (apolipoproteins).

Front 9

The structure of serum lipoproteins are spherical particles with a core and a shell. Explain these components.

Back 9

Core- triglycerides and cholesterol esters (non-polar core)

Shell- monolayer of phospholipids and cholesterol form the amphipathic shell (apolipoproteins imbedded in the shell)

Stable due to hydrophobic interactions

Front 10

Apolipoproteins provide metabolic signaling for various classes of plasma lipoproteins and may serve as ___.

Back 10

Cofactors
Ligands
Lipid exchange proteins

Front 11

What is the order of the lipoproteins from size and density? Lowest to highest?

Back 11

Chylomicrons- triglyceride core
VLDL- triglyceride core (some cholesterol esters)
LDL- cholesterol ester core
HDL- cholesterol ester core

Front 12

Apoproteins:

Chylomicron

Back 12

B-48, C-II, and E

Front 13

Apoproteins:

VLDL

Back 13

B-100, C-II, and E

Front 14

Apoproteins:

IDL

Back 14

B-100, C-II, and E

Front 15

Apoproteins:

LDL

Back 15

B-100

Front 16

Apoproteins:

HDL

Back 16

A, C-II, and E

Front 17

What does lipoprotein lipase do? And what is it activated by?

Back 17

Extracellular. On capillary walls of adipose cells. Takes up FA while glycerol returns to the liver. Activated by Apo C-II.

Front 18

What does hepatic triacylglycerol lipase do (HTGL)?

Back 18

Recognized IDL (for transport and degradation in the liver).

Front 19

What about LCAT/PCAT?

Back 19

LCAT- Lecithin-Cholesterol Acyl Transferase. Activated by Apo A-1 and specific for HDL. Takes cholesterol from extrahepatic tissues and adds lecithin (from inside the HDL) and forms a cholesterol ester.

Front 20

What is CETP?

Back 20

Lipid transfer protein. Transfers cholesterol from HDL to VLDL. Also, transfers phospholipids and TG from VLDL to HDL.

Front 21

ACAT does what? And is located where?

Back 21

ACAT- Acyl-CoA Cholesterol Acyl Transferase. Located inside the cells; NOT in the serum. Stimulated by elevated intracellular cholesterol. Produces cholesterol ester for intracellular storage (uses one fatty acyl CoA).

Front 22

Special receptors recognize lipoproteins on the intravascular carriers. The following cards are a list of receptors. Explain what cells they are on and what they recognize.

1. LDL receptor

Back 22

MOST cells

recognizes ApoB-100

Front 23

2. Scavenger Receptor Type B Class I (SR-B1)

Back 23

Liver, and steroidogenic tissue

recognizes HDL

Front 24

3. Chylomicron remnant receptor

Back 24

LIVER

recognizes ApoB-48 and ApoE

Front 25

4. SR-A1 and SR-A2

Back 25

Macrophages

LDL- damaged?

Front 26

Chylomicrons are used as a vehicle for transporting dietary lipids from intestine. Their synthesis and assembly is in what type of cells?

Back 26

Intestinal mucosal cells.

Front 27

Chylomicrons contains TG, cholesterol, and ApoB-48 as nascent cells leaving the intestinal mucosal cells. What gives them two more apoproteins? And what are those proteins?

Back 27

HDL give them ApoE and ApoC.

Front 28

TG in chylomicrons are formed from what dietary components?

Back 28

MAG and 2FA-CoA

Front 29

The majority of TG are taken up into muscle and adipose cells as ___. The remnants of the chylomicron are then shuttled back to the ___ with cholesterol being more than TG.

Back 29

FFA; liver.

Front 30

Chylomicron remnant receptor recognizes what apoproteins? In what tissue? What apoprotein does the chylomicron "give back" to HDL?

Back 30

ApoB-48 and ApoE in liver. Gives back ApoC. REMEMBER! The ApoC is important for lipoprotein lipase recognition.

Front 31

VLDL originates in the ___ and is synthesized under what conditions?

Back 31

VLDL is synthesized in the liver and is made during caloric excess, and is stimulated by insulin, estrogen, and EtOH.

Front 32

It initially packages what two things and what is it's initial apoprotein?

Back 32

Cholesterol esters and TG. With ApoB-100.

Front 33

It receives what two additional apo from what?

Back 33

ApoE and ApoC from HDL. Remember the ApoC is needed for lipoprotein lipase recognition.

Front 34

What is the destination of VLDL?

Back 34

TG storage in adipose. FA oxidation in most cells.

Front 35

VLDL remnants are transfered to liver or converted to ___.

Back 35

LDL.

Front 36

Again... the ApoC and ApoE are transfered back to ___ when VLDL makes LDL?

Back 36

HDL. LDL is originally just ApoB100. No ApoE or ApoC.

Front 37

LDL can either go back to the ___ by use of LDL receptors that recognize Apo___. OR LDL can go to ___.

Back 37

liver; ApoB-100; or go to peripheral cells which also recognize ApoB-100.

Front 38

IDL hits the hepatic lipase receptor in the liver to be converted into LDL. This is stimulated by what three things?

Back 38

Insulin
Thyroxin
Steroids

Front 39

The main component of LDL is what?

Back 39

CE, but it does have some TG.

Front 40

LDL's primary destination is what? What does NOT accept it?

Back 40

Primary- epithelium of blood vessels and liver
NOT- brain and blood cells

Front 41

What is HDL's function?

Back 41

Return of peripheral tissue cholesterol to the liver and source of exchange for apoproteins.

Front 42

HDL exchanges CE for what? With what carriers?

Back 42

For TG and C; in VLDL and LDL.

Front 43

HDL is mostly ___ due to ApoA and LCAT.

Back 43

CE

Front 44

What transfers the CE to LDL and VLDL from HDL?

Back 44

CETP- CE transfer protein

Front 45

Type I Hyperlipidemia

Back 45

Deficiency in lipoprotein lipase (metabolizes TG to FA) or ApoC-II (activates chylomicrons). Causes high serum triglycerides due to accumulation of chylomicrons.

Front 46

Type II Hyperlipidemia

Back 46

Deficiency in LDL receptor. High serum cholesterol and ester due to the LDL accumulation. No downregulation of cholesterol biosynthesis causes cholesterol accumulation. These people die early on due to stroke and heart attack.

Front 47

Type III Hyperlipoproteinemia

Back 47

Failure to clear chylomicron remnants. Due to defect in Apo-B48 and/or liver receptor.

Front 48

Fatty Liver

Back 48

Increase TG and problems with VLDL secretion. Causes damages to liver. Can occur in diabetes II and alcohol abuse.

Front 49

Diabetes

Back 49

glycation of LDL (bound to PE)

LDL covalently linked to glucose
PE binds
LDL is therefore "damaged"
Macrophage take up and get big, then stuck in endothelium of capillary, die and start plaque formation. Causes atherosclorosis.

Front 50

CAD- Coronary Artery Disease

Back 50

Oxidative stress can damage LDLs. The damaged LDLs are still recognized by macrophages due to there SR-A1 and SR-A2 receptors (but not by LDL receptors). Clearing the excess cholesterol causes FOAM cells which get stuck in the epithelium, causes inflammation and plaques.

Front 51

What does cholystyramine?

Back 51

Binds bile salts and prevents re-absorption by intestine. Lowers LDLs. Prevents re-uptake.

Front 52

What do the statins do?

Back 52

Prevent synthesis of cholesterol. Inhibit our friend HMGCoA Reductase.

Front 53

Secondary effects of statin therapy.

Back 53

Decrease cell proliferation and oxidative stress that causes plaque rupture. It also increases eNOS levels which increase NO resulting in vasodilation which prevents ischemic stroke in brain arteries. SEE page 108 for more detail.

Front 54

Recap an Important Siefert point:

Why are damaged LDL's so dangerous?

Back 54

Because macrophages can take up via an UNREGULATED means. Receptors SR-A1 and A2 on the macrophage take these LDL's up and this can lead to FOAM cells (enlarged macs that get stuck in the endothelium of the vessels).

Front 55

Recap an Important Siefert point:

What is the job of the HDL?

Back 55

Takes up cholesterol from the periphery and converts into CE. This can be given to the VLDL and LDL in exchange for MORE C, Ph, and TA.

Front 56

Recap an Important Siefert point:

Are CE in the core or shell?

Back 56

CORE

Front 57

Recap an Important Siefert point:

Are C in the core or shell?

Back 57

SHELL

Front 58

Recap an Important Siefert point:

What activates LCAT?

Back 58

ApoA in HDL