FSHN 350 - Lipids (Unit 3.1)

What is a lipid?

- a group of organic compounds
- insoluble

Whats the function of lipids?

- energy storage
- insulation
- cell membrane structure
- can make other compounds - bile, Vit. D, steroid hormones

Types of lipids

- fatty acids
- triacylglycerol
- phospholipid
- cholesterol

What is the simplest lipid

- fatty acid

Fatty Acid structure

- polar head (hydrophilic) -- alpha/delta end (carboxy)
- nonpolar tail (hydrophobic) -- omega end (methyl)

3 types of classification

1. length of the chain
2. degree of saturation
3. essential/nonessential

Length of the chain

- how many C's are in the chain
- short -- less than 6C
- medium -- 6-12C
- long -- 13-24C
- length determines how FA are digested/metabolized

Degree of saturation w/ H

- saturated fatty acids
- unsaturated fatty acids

Traits of saturated FA

- typically solid at room temp
- butter, lard
- no double bonds

Traits of unsaturated FA

- can be monounsaturated and polyunsaturated
- is more flexible
- part of cell membranes
- has double bonds between C's

Monounsaturated FA

- has only one double bond

Polyunsaturated FA

- has multiple double bonds

Essential/nonessential

- essential - cannot be made in the body (consumed)
- essential - linoleic and a-linolenic
- nonessential - made in the body

FA naming system

1. common system
2. omega system
3. delta system

Omega system: need to know

- # C
- # double bonds
- # C to the first double C, from the Omega (methyl) end

Delta system: need to know

- # C
- # double bonds
- # C to each double C, from the Delta (carboxy) end

How to name FAs

- figure out the common name
- Omega -- count the C's, count to first double C
- Delta -- count the C's, count to each double C

alpha-linolenic acid

- OMEGA 3

linoleic acid

- OMEGA 6

How to make essential FA

- desaturation
- elongation

What is desaturation?

- create double bonds
- add to Delta end
- Delta 9 is the highest desaturase in the body
- via desaturase enzymes

What is elongation?

- 2 C added to Delta end
- via elongase enzymes

How to make Oleic acid?

- stearic acid --> oleic acid
- use desaturase 9
- add double bond on 9 C (from Delta end)

How to modify linoleic acid

- forming arachidonic acid
- desaturate at Δ6 via desaturase Δ6
- elongate 2C
- desaturate at Δ5 via desaturase Δ5

How to modify a-linolenic acid

- forming EPA
- desaturate at Δ6 via desaturase Δ6
- elongate 2C
- desaturate at Δ5 via desaturase Δ5

Saturated FA's

- butyric acid - 4C
- myristic acid - 14C
- palmitic acid - 16C (most common FA)
- stearic acid - 18C

Unsaturated FA's

- oleic acid - 18C
- linoleic acid - 18C
- a-linolenic acid - 18C
- arachidonic acid - 20C
- EPA - 20C

Why can't we make a-linolenic or linoleic?

- the body does not have a desaturase above Δ9

Cis vs Trans double bonds

- cis -- same side of double bond -- creates kinks
- trans -- opposite side of double bond -- straight structure

Cis vs Trans

- cis is most common in nature
- trans is manufactured b/c cheaper + longer shelf life

What do trans fats do?

- increase risk of HD

How to form a triacylglycerol

- 1 or more FA
- 1 glycerol
- one ester bond

What are triacylglycerols?

- main storage in the body
- account for 95% of dietary fat intake

What is a sterol?

- a 4-ring structure
- the most common form in cholesterol

What is cholesterol used for?

- essential for cell membranes
- two forms: esterified form and free form

Cholesterol percents

- 75% made in body
- 25% from diet

How is cholesterol stored

- in its esterified form
- esterified = add an FA

How does bile lower cholesterol?

- cholesterol is in bile
- bile meds forces bile to be excreted
- but the body has a certain amount of bile needed
- so the body needs more and pulls cholesterol from the blood to make more bile

Phospholipids

- 1 phosphate
- 1 or more FA
- important for cell membrane
- core = glycerol or sphingolipids

How are lipids digested?

- fat is emulsified

Emulsification

- break big fat into smaller fat
- emulsification = increase Surface Area
- happens in SI via bile

Steps of digestion

- mouth
- stomach
- small intestine

The mouth

- we eat the lipid
- lingual lipase via salivary glands starts to pull off fatty acid from triacylglycerol
- only 10% digestion happens in mouth

The stomach

- gastric lipase pulls off a few more fatty acids
- mouth + stomach = max 30% digestion

The small intestine

- Phase 1 - emulsification
- Phase 2 - digestion

Phase 1

- bile breaks lipid globule into smaller globules (micelles)

Phase 2

- pancreatic lipase (via pancreas) removes more FA
- make monoacylglycerols + FA

What are in micelles

- Triacylglycerol (TAG)
- Phospholipids
- Cholesterol
- FA and monoacylglycerols (from the mouth and stomach)

Where does most of lipid digestion occur

- in the intestine via pancreatic lipase

Lipid digestion in the micelle

- the micelle has phospholipids, triacylglycerol and cholesterol
- the enzymes, phsopholipise A2, pancreatic lipase and cholesteryl ester hydrolase enter and work on all lipids

What happens after digestion in the micelle

- the lipids leave micelle and enter the enterocyte
- lipids reform and then form chylomicrons

What is Bile

- made in liver
- stored in gallbladder
- stimulated by CCK
- breakdown fat

Phospholipid and cholesterol digestion

- phospholipid - broken down by phospholipase A2
- cholesterol - broken down by cholesteryl ester hydrolase

Short/Medium FA chains

- can be directly ingested into the SI cells

Short chains

- made by microbes
- do not form chylomicrons
- bind to protein albumin -- making it hydrophilic enough to enter the blood
- b/c it enters the blood, it can go to the mitochondria which leads to ATP production
- short is better than long chains

How do small and medium chains get into SI

- easily absorbed into the SI cell

How do long chains get into SI

- via micelles
- fat emulsified and taken up into the cell

Where do long chains go after the enterocyte

- the lymph

Where do short and medium chains go after the enterocyte

- the blood

3 differences between small and long chains

- short are not as hydrophobic
- short are not transported via chylomicrons
- short can diffuse directly into intestinal cells

What are lipoproteins

- transporters of fat

What are apoproteins

- proteins that are on lipoproteins
- they have a letter and a number

Types of lipoproteins

- VLDL
- IDL
- LDL
- HDL
- chylomircron

Lipoprotein composition

- VLDL -- mostly triacylglycerol
- IDL -- mostly triacylglycerol and cholesterol
- LDL -- mostly cholesterol
- HDL-- mostly protein and cholesterol
- chylomircron -- mostly triacylglycerol

What is a chylomicron?

- transporter of dietary triacylglycerols

Function of chylomicron

- deliver dietary triacylglycerols to tissues

When do chylomicrons move

- after we just ate
- in the FED state

Where are chylomicrons made

- in the small intestine

Chylomicron apoproteins

- apoB48
- apoCII
- apoE

Cholesterol Meds

- bile decreases blood cholesterol story
- HMG CoA reductase that blocks formation of cholesterol

apoB48 function

- a structural apoprotein that stabilizing the chylomicron in an aqueous environment

apoCII function

- activates lipoprotein lipase (LPL)
- stimulates lipolysis of triacylglycerol

apoE function

- allows uptake of chylomicron into liver via the LDL-receptor or by LDL-receptor-related protein

Where does chylomicrons enter

- they enter the lymph and goes to the blood

Chylomicron story

- lipids are reformed in the intestine
- lipids formed into chylomicrons (with apoB48)
- leave the intestine (enter lymph) --> nascent chylomicron
- nascent chylomicron meet up with HDL
- HDL donates apoCII and apoE
- mature chylomicron go to tissues
- apoCII stimulates LPL to offload FA into the tissues (glycerol to liver)
- apoCII given back to HDL
- remnant chylomicron (apoB48 + apoE) head back to the liver
- apoE binds to LDL receptor, allowing it into the liver
- liver breaks down chylomicron to be recycled

How to increase Heart Disease?

- decrease apoE = fatty blood
- no LDL receptor = fatty blood
- lipids in blood = risk factor for HD

What happens if you inhibit LPL

- you don't become obese b/c no fat enters the cell
- instead, you have fatty blood
- blood gets under the blood vessels --> can lead to plaque
- pretty common

Entire story (chylomicron)

- we eat food, it gets digested
- lingual lipase pulls off some FA (mouth)
- gastric lipase pulls off some FA (stomach)
- phase 1 - bile emulsifies: break big fat globules into smaller ones (micelles)
- phase 2 - pancreatic lipase pulls off some more FA
- micelles enter the enterocyte (SI)
- triacylglycerols, phospholipids, cholesterol reformed in SI cell
- lipids formed packaged chylomicrons (with apoB48)
- leave the intestine (enter lymph) --> nascent chylomicron
- nascent chylomicron meet up with HDL
- HDL donates apoCII and apoE
- mature chylomicron go to tissues
- apoCII stimulates LPL to break TAG into FA
- LPL offloads FA to the tissues (glycerol to liver)
- apoCII given back to HDL
- remnant chylomicron (apoB48 + apoE) head back to the liver
- apoE binds to LDL receptor, allowing it into the liver
- liver breaks down chylomicron to be recycled

Two functions of triacylglycerols in tissues

- can be stored
- can be used to produce ATP

What is TAG

- triacylglycerol

What is VLDL

- transporter of endogenous triacylglycerol
- TAG produced from the body

Where is VLDL made

- in the liver
- inhibited by insulin

VLDL apoproteins

- apoB100
- apoE
- apoCII

apoB100 function

- a structural apoprotein
- ligand that binds to LDL receptor

VLDL story (entire)

in liver
- nascent VLDL (w/ apoB100) leaves the liver
- nascent meets up with HDL
- HDL gives apoE and apoCII
- VLDL goes to extrahepatic tissues (fat, muscle, etc)
- apoCII activates LPL to release FA to the tissues (glycerol goes to liver)
- VLDL gives HDL apoCII
- as TAG leaves VLDL: VLDL becomes IDL
- IDL has little TAG and no apoCII
- more loss of TAG = LDL
- two pathways
- IDL (apoB100 + apoE) can go to the liver
- apoB100 or apoE bind to LDL receptor --> recycled by liver
- LDL (apoB100) can go to extrahepatic tissues and donate cholesterol OR can just go to the liver
- ultimately return to liver to be broken down

LDL forward cholesterol transport

- the major cholesterol carrier
- formed from IDL in blood
- going to extra-hepatic tissues

LDL into the liver

- LDL binds to LDL receptor -- apoB100
- binding leads to endocytosis of LDL
- once in the cell, break down into free cholesterol

3 ways body keeps free cholesterol levels low

once cholesterol levels start to increase
- increase cholesterol storage
- decrease cholesterol synthesis
- decrease LDL receptor synthesis

Increase cholesterol storage

- stick FA onto cholesterol via ACAT enzyme

Decrease cholesterol synthesis

- lower cholesterol concentration by blocking HMG CoA reductase
- HMG is the enzyme that makes free cholesterol

Decrease LDL receptor synthesis

- make less so LDL can't bind and dump its cholesterol

What apoproteins does the LDL receptor recognize

- apoB100
- apoE

Function of HDL reverse cholesterol transport

- removes cholesterol from cell to the liver
- HDL secreted from liver and small intestine

How HDL reverse cholesterol transport works

- enzyme ABC1 facilitates movement of cholesterol from tissue to HDL
- apoA1 activates LCAT
- enzyme LCAT esterifies cholesterol (add FA)
- cholesterol with apoA1 = mature HDL
- go into the liver

Role of liver in lipid metabolism

- make bile
- make lipoproteins
- make new lipids
- breakdown 70% LDL
- breakdown chylomicron remnants and repackage into HDL and LDL

Blood lipids

units mg/dL
- Total cholesterol (high) -- 240
- LDL (high) -- 160
- HDL (low) -- 40 :: want HDL over 60
- Triacylglycerols/VLDL (high) -- 200

Blood lipids high or low

- high = that the value is the cutoff for being too high
- low = that the value is the cutoff for being too low
- too low or high is bad => doc should put you on meds

Lipoprotein review table

created/carries/goes/broken down
VLDL -- liver -- endogenous TAG -- extrahepatic -- liver
- Chylomicron -- SI -- dietary TAG -- extrahepatic -- liver
- IDL -- blood from VLDL -- TAG -- extrahepatic -- liver
- LDL -- blood from VLDL/IDL -- cholesterol -- extrahepatic -- liver
- HDL -- liver/intestine -- cholesterol/proteins -- extrahepatic -- liver

Butyric acid name

- delta: C4:0
- omega: C4:0

Myristic acid name

- delta: C14:0
- omega: C14:0