CFB 16: Fatty Acids (Biochemistry)

Are lipids hydrophobic or hydrophilic?

Hydrophobic

Lipids associate with ____ _____, excluding water.

Each other

What are the roles of fats?

Provide energy
TAG fat stores energy
Membrane lipids
Protein modification
Signaling lipids

2 major classes of lipids

1. Isoprenoids
2. Fatty acids

Isoprenoids are synthesized out of _________ units.

Isoprene

What is the typical example of an isoprenoid?

Cholesterol

Examples of isoprenoids

Bile acids/salts
Membranes
Hormones
Cofactors
Fat soluble vitamins

Isoprenoid names

Testosterone
Estradiol
Cortisol
Aldosterone
Prednisolone
Prednisone

Are fatty acids charged?

Yes

T/F: Fatty acids are amphipathic.

True

What makes up fatty acids?

Carboxyl group + unbranched alkyl hydrocarbon chain

Where is the alpha carbon?

The carbon that is adjacent to the carbon of the carbonyl group

Where is the omega carbon?

At the very end of the carbon chain, furthest from the carboxyl group

What are fatty acids used for?

Energy storage (and fat deposits cushion organs and insulate against heat loss)
Membranes (and electrical insulation of nerves) including phospholipids and sphingolipids
Signals

How long are long chain fatty acids?

>12 carbons

How long are medium chain fatty acids?

6-12 carbons

How long are short chain fatty acids?

<6 carbons

Where are long chain fatty acids absorbed?

Small intestine

Where are medium chain fatty acids produced?

Mammary gland

Medium chain fatty acids are used in treatment of...

Waldmann disease
Epilepsy
Chronic pancreatitis

Where are short chain fatty acids produced?

Colon by microbiome

Which fatty acids can cross the blood brain barrier?

Short chain

Which fatty acids account for 6-10% of total energy, 80% in coloncytes?

Short chain

What is the symbol of stearic acid?

18:0

What is the systematic name of stearic acid?

Octadecanoic acid

How do you name a fatty acid?

Numbering: carboxyl carbon = 1
- Omega carbon at the end C and alpha at C2

How do you make the FA symbol?

# before colon = total length of chain
# after colon = # double bonds
Superscript = list of double bond positions

What is the symbol of palmitic acid?

16:0

At neutral pH, FAs are _______ and act as ______.

Charged; soaps

Is stearic acid saturated or unsaturated?

Saturated, 18:0

Oleic acid nomenclature

18:1Δ^9

Is oleic acid saturated or unsaturated?

Monounsaturated

α Linolenic acid FA symbol

18:3Δ^9,12,15

How do you calculate the omega numner?

Number of carbons from the terminal methyl (ω) carbon to the nearest double bond
ω# = (# of carbons) - (carbon # starting last double bond)

How to calculate omega number of α Linolenic acid

18:3Δ^9,12,15

18 - 15 = ω3

How to calculate omega number of Linoleic acid

18:2Δ^9,12

18 - 12 = ω6

Linoleic and linolenic are _________ fatty acids.

Essential

Symptoms of linoleic and linolenic fatty acid deficiency

Scaly dermatitis, alopecia, thrombocytopenia (low platelet count), cognitive development

What determines physical properties of FA-containing compounds?

Fatty acid melting point

Melting points of uncharged FAs (R-COOH) increase with what?

Chain length

Why do long chain FAs have higher melting points?

More Van der Waals contacts

Effect of double bonds on FA melting point

Double bonds decrease melting point

Is melting point lower or higher in cis fatty acids?

Cis: lower melting point than trans

When do lipid micelles form?

At critical micelle concentration (CMC)

From the CMC and on, everything added ends up in a _______.

Micelle

Fatty acids esterified to glycerol

Triglycerides

What fatty acids are often esterified?

Glycerol and sphingosine

Name the structure of arachidonic acid.

20:4Δ^5,8,11,14
ω6

What percent of US caloric intake is fat (vs. what is recommended)?

35-40%
20-35%

What is the major source of US caloric fat intake?

Triglycerides

What chews up medium chain FAs in the mouth?

Lingual lipase

What does CCK do?

Makes pancreas release pancreatic lipase

What is key to hydrolysis of TAGs?

Pancreatic lipase

Pancreatic lipase has an important protein cofactor called ________.

Colipase

Why is full hydrolysis of pancreatic lipase not necessary?

The two hydroxyl groups on 2-MAG make it sufficiently soluble in water

Does pancreatic lipase recognize olestra?

No!

T/F: Pancreatic lipase can easily access fat droplets.

False

What is required for pancreatic lipase to access fat droplets?

Emulsification by amphipathic lipid

What does gallbladder release?

Bile salts (cholesterol derivatives) and phospholipids

What does pancreatic lipase produce?

Free FA salts (soaps)
2-MAG

Bile acids made from cholesterol in the liver are converted to...?

Bile salts

80-95% of bile salts are recycled via...?

Enterohepatic circulation

What does cholestyramine do?

Prevents recycling
Causes loss of bile salts to feces

What happens when bile salts are not released through bile duct from gallbladder?

Biliary obstruction

What can lead to gallstones?

Imbalance of cholesterol, bile salt, and phospholipid secretion

What causes these symptoms?

Steatorrhea in chronic cases

Deep recurrent moderate to severe abdominal, back, or epigastric pain exacerbated by alcohol

Nausea and vomiting

Elevated serum lipase and serum amylase

Pancreatitis

Lipid digestion disorders lead to...?

Malabsorption/steatorrhea

What happens if bile salts are not released through bile duct from gallbladder?

Biliary obstruction

What happens if there is no release of pancreatic lipase?

Pancreatic disease

Which statement about bile acids and salts is correct?

Using a drug to prevent the reabsorption of bile acids and salts from the intestine causes the liver to increase metabolism of cholesterol

Using a drug to prevent the reabsorption of bile acids and salts from the intestine causes the liver to do what?

Increase metabolism of cholesterol

Micelles diffusing to surface release _______ and ____ that are taken up.

LCFAs and MAG

Cholesterol transport is ________ mediated.

REceptor

What does ezetimibe do?

Inhibits cholesterol absorption by inhibiting NPC1L1

What is NPC1L1?

Cholesterol receptor

T/F: Fatty acids diffuse into the circulation.

False

Fatty acid transport to the body begins with what?

TAG re-synthesis

What enzymes re-synthesize TAG?

1. Fatty acyl-CoA synthetase
2. Triacylglycerol synthase

What does ACAT do?

Re-esterification of cholesterol
(Acyl-Cholesterol Acyl Transferase)

How do FAs/triglycerides get into the system?

Short and medium chain molecules absorbed in portal circulation

What do chylomicrons do?

Transport long chain FAs, cholesterol, and fat-soluble vitamins from intestinal cells to the liver and other tissues

What is the largest lipoprotein particle?

Chylomicron

How do chylomicrons alter serum color?

Milky appearance

Where does chylomicron formation begin?

ER

Where are TAGs and CEs synthesized?

Between the phospholipid bilayers of ER membranes

Membrane bound lipid droplets bud into the __ lumen.

ER

What is added in order to form a nascent chylomicron?

Apolipoprotein ApoB48

What is a nascent chylomicron?

Lipoprotein

What protein loads chylomicrons?

Microsomal Triglyceride Transfer Protein (MTP)

What happens if you cannot load the lipid onto the chylomicron?

The system will back up

What is an MTP deficiency characterized by very low blood triglyceride and total cholesterol levels?

Abetalipoproteinemia (aka Bassen-Kornzweig disease)

Nascent chylomicrons are transported from where to where?

ER → Golgi apparatus

Vesicles from the Golgi fuse with the cell membrane, releasing what into where?

Chylomicrons into lymphatic system

Chylomicrons are released into the lymphatic system through what?

Lacteals

Where do lacteals lead to?

Subclavian vein

Nascent chylomicrons exchange with ___ to mature.

HDL

What does ApoC-II activate?

Lipoprotein lipase on blood vessel inner surface (adipose and other tissues)

Where is lipoprotein lipase (LPL) found?

Epithelial surfaces

Where is LPL synthesized?

Parenchymal cells

Where is LPL trafficked to?

Endothelial surface