Lipid Metabolism 3-4 (1)

What is it called when a substance is both hydrophobic and hydrophilic?

Amphipathic

Is a lipid hydrophobic or hydrophilic?

Hydrophobic

In a tri-ester of glycerol, where is the beta carbon located?

It is the second carbon of the chain

Lipoproteins require what type of lipids?

Amphipathic

Which side of the fatty acid faces the water?

Hydrophilic side

Why do lipoproteins require amphipathic lipids?

Require amphipathic lipids so it can dissolve

Define amphipathic

Has both hydrophilic and hydrophobic properties

What can go inside the micelle?

lipid

What are the two structures that phospholipids make up?

Membrane lipid bilayer
Outer shell of lipoproteins

Alcohols and phosphatidic acid form...

glycero-phospholipids

Because inositol has a lot of (blank) it can add hydrophilicity

alcohol

Inositol has a lot of alcohols and thus can add (blank)

hydrophilicity

In the general structure of a micelle, what is found on the outside of the micelle?

hydrophilic polar heads

In the general structure of the micelle, what is found on the inside of the micelle?

Hydrophobic tails

In a mixed micelle (pseudomicelle), what is in between the FA heads?

OH is in between the FA heads

In a mixed micelle, what is esterified and moves to the core of the mixed micelle?

Cholesterol

In a mixed micelle, what is the shell composed of?

Multiple amphipathic substances

In a pseudomicelle, what is dissolved in the center region?

A nonpolar substance is dissolved in the center region

Name two totally hydrophobic lipids

Triglycerides and cholesterol esters

What are 3 similarities in serum lipoproteins?

All transport lipids
All are mixed pseudo-micelles
Lipids and proteins

In a pseudo-micelle, what 3 things are in the shell?

Phospholipids, cholesterol, and fatty acid shells

In a pseudo-micelle, what two things are in the core?

tryglycerides and cholesterol esters

What kind of interactions are formed between lipids and proteins found in serum lipoproteins?

Non-covalent interactions

What are 3 differences among serum lipoproteins?

Contents of core
Types of apolipoproteins
Type of lipid carried

What are the differences in the contents of serum lipoprotein cores?

Tryglyceride rich versus Cholesterol rich

What are the two types of lipids carried by serum lipoproteins?

Endogenous (liver made)
Exogenous (dietary)

Name the lipoprotein carrier of tryglyceride

Chylomicrons

Where are fatty acids oxidized?

In the muscle

What does a tryglyceride have to be broken down into before it can be absorbed?

TG must become 2-MG and FA before it can be absorbed and changed back into TG for transport

Which is largest: chylomicron, VLDL, LDL, or HDL?

Chylomicron

True/False: Chylomicrons and VLDL are rich in cholesterol esters

False! Chylomicrons and VLDL are rich in tryglycerides

True/False: LDL and HDL are rich in tryglycerides

False! They are rich in cholesterol esters

What does HDL carry?

Cholesterol and protein

What 3 types of lipoproteins are rich in tryglycerides?

Chylomicrons, VLDL, and IDL

What 2 types of lipoproteins rich in cholesterol esters?

LDL and HDL

After becoming a remnant, VLDL then...

becomes IDL and goes to the liver OR becomes LDL

After becoming a remnant, chylomicrons...

go to the liver

In an electrophoresis of fasting plasma, two things do not appear

Chylomicrons and VLDL do not appear on the pattern

In an electrophoresis of fed plasma, what appears

Marks for chylomicrons (lipid ingestion), VLDL (sugar ingestion), LDL, and HDL

TG combines bile salt to make...

Micelle

Micelle and colipase-lipase become...

FA and 2-MG

Without Bile salts, TG cannot form..

Micelle, thus cannot break down and be absorbed as FA and 2-MG

Name the breakdown product of TAG absorbed into the intestinal cells

2-MG (aka B-MG)

How does orlistat work?

Inhibits pancreatic lipase, preventing the change from TG to 2-MG, thus preventing absorption

What does Fatty Acyl CoA Transferase do to B-MG?

Uses its high energy to attach legs to glycerol backbone of B-MG, forming TG

What is the fate of the vast majority of cholesterol?

Vast majority of cholesterol becomes bile salts

What is the major site for endogenously made lipids?

Liver is the major site, at 50%

What are the 3 sites for endogenously made lipids?

Liver (50%)
Intestine (15%)
Extrahepatic ie skin (35%)

What is all cholesterol made from?

3 acetyl-SCoA

What is the regulatory step of cholesterol synthesis?

HMG to Mevalonic acid by using HMG CoA Reductase

What blocks the regulatory step of cholesterol synthesis?

Statin blocks the reaction by inhibiting HMG CoA Reductase

What causes blockage of the reductase pathway in cholesterol synthesis?

Excess cholesterol blocks the reductase regulatory step in cholesterol synthesis by negative feedback

Name 3 types of amphipathic lipids

Fatty acids
Phospholipids
Cholesterol

What is the purpose of Niemann-Pick C1-like transporter?

NPC1 transports free cholesterol from the blood to the intestinal epithelial cell

What is the function of ABC1 transporter?

To transfer free cholesterol from the intestinal epithelial cell to the blood

What is Tangier disease?

Deficiency in ABC1 transporter.

What kind of lipoprotein is lacking in Tangier disease?

HDL is deficient, because free cholesterol needed for its synthesis cannot escape the intestinal epithlial cell

What is NPC1 disease also called?

Lysosomal storage disease, which causes accumulation of cholesterol in lysosomes and prevents release

Cholesterol and fatty acyl CoA, when combined with ACAT, create...

Cholesteryl ester

Memorize slide 51 from this lecture

...

Where is HDL made and what does it require?

HDL is made in the blood and requires cholesterol

How are nascent chylomicrons formed?

Combine TG from SER and AopB from RER to make chylomicron

How are nascent chylomicrons secreted?

By exocytosis out of the golgi complex

How do nascent chylomicrons mature?

Take ApoCII and ApoE from HDL to mature

What proteins are transferred from HDL to nascent chylomicrons during maturation stage?

ApoCII and ApoE

What are the 4 steps to the fate of chylomicrons?

Lipoprotein lipase activated by ApoCII
Digestion of TG to FA
FA oxidized (muscle) and stored (adipose)
Remnants

Where is the major site for TG synthesis in the cells?

Liver

Which apolipoprotein is absolutely required for formation of VLDL?

ApoB100

Where is ApoB-48 found?

Chylomicron

Where is ApoB-100 found?

VLDL, LDL, and IDL

Where is cholesterol located in VLDL?

In the shell as cholesterol and in its core as cholesterol ester

Why is ApoB-100 found in VLDL, LDL, and IDL?

BEcause VLDL becomes IDL which can then become LDL

True/False: LDL has ApoCII and ApoE?

False, it has neither

True/False: VLDL and IDL have ApoCII and ApoE

True

True/False: ApoB-100 is found in VLDL, LDL, and IDL

True

Where is VLDL made?

In the liver

Where is LDL made?

In the blood

How do NPC1 inhibitors work as anti-cholesterol drugs?

Inhibiting NPC1 prevents uptake of cholesterol from blood to intestinal epithelial cell

How does the ABC1 mutation lead to Tangier disease / low HDL?

The ABC1 mutation inhbits ABC1 transporter, preventing release of cholesterol into blood from intestinal epithelial cell. HDL needs blood cholesterol to form and Tangier disease is charecterized by low levels of HDL in blood. Thus, inhibiting ABC1 transporters lowers HDL and causes Tangier disease.