Fatty Acids

Question 1

Components of a FA

Answer 1

Tail = hydrophobic/hydrocarbon chain

Head = terminal carboxylic acid
-forms ester bonds with OH groups on glycerol to form TGs

Question 2

End product of FA beta-oxidation

Answer 2

Acetyl-CoA

—> can then make ketone bodies

Question 3

Saturated vs. unsaturated

Answer 3

Saturated = 100% reduced (no 2x bonds)…solid at RT…more unhealthy

Unsaturated = 2x bonds…liquid at RT…

Saturated = higher melting temperature

Question 4

Fluidity

Answer 4

Referring to phospholipids in cell membranes

If FA components are saturated = less fluidity in membrane

Question 5

Alpha vs. beta vs. omega carbon

Answer 5

2 = alpha

In one naming system…

Carbob #1 = on carboxylic acid

Last (CH3) = omega

Double bonds (18:1 delta9) - means double bond starts on the 9th carbon

Question 6

“-enoic” vs. “-anoic”

Answer 6

• enoic = unsaturated

- anoic = saturated

Question 7

Most common saturated FAs

Answer 7

Palmitic (palm oil and meat; C16:0)

Stearic (meat and cocoa butter; C18:0)

Diets rich in sat fats are increase risk for atherosclerosis, coronary heart disease, and stroke, and (-) effect on cholesterol profile

Recommended to limit to <7% of daily caloric intake

Question 8

Common monosaturated FAs

Answer 8

Palmitoleic (C16:1; animal, veggie, and marine oils)

Oleic (C18:1, many oils…most abundant monosat in adipose tissue)

Question 9

Common polyunsat FAss

Answer 9

Alpha-linolenic/ALA (18:3, omega-3, essential)

Linoleic (18:2, omega-6, essential)

Eicosapentaenoic/EPA (20:5, omega-3)

Docoahexaenoic/DHA (22:6, omega -3)

Arachidonic/ARA (20:4, omega-6)

Question 10

Generally…

Animal sources =

Veggie sources =

Answer 10

Animal = sat and mono

Veggie = poly

Question 11

Hydrogenating unsaturated FAs —> result?

Answer 11

Increase shelf life of food

Reduces cis bonds

INCREASES TRANS-BONDS = BAD for health (cardio risk)

Question 12

Omega fats

Answer 12

Omega- 3 (ALA, EPA, DHA)
Omega - 6 (linoleic, ARA)

Important for growth and inflammatory response

DHA = essential or required nutrient in the brain and retina for optimal neuronal functions at all developmental stages

DHA + EPA = beneficial in the prevention and management of cardio disease and other chronic disorders

Question 13

Competition between omega3 and 6 FAs

Answer 13

Use same synthesizing enzymes

In a typical western diet = 10x-30x omega 6 than 3

—> can have a loss of health benefits of omega-3s (recommended 1:1 to 4:1)

Best way to do this is through direct consumption (especially during preg and lactation)

Question 14

Essential FAs

Answer 14

Cannot be made de novo…must be obtained in diet

Alpha-linoleic (18:3, omega3) = precursor to EPA and DHA

Linoleic (18:2) = precursor to ARA, which is the substrate for prostaglandin synthesis…in linoleic is low —> arachidonic acid becomes essential

Question 15

16:0

Answer 15

Pamitic

Question 16

18:0

Answer 16

Stearic

Question 17

18:1

Answer 17

Oleic

Question 18

Alpha-linoleic

Answer 18

18:3, omega3

Question 19

Docosahexaenoic (DHA)

Answer 19

22:6, omega3

Question 20

Linoleic

Answer 20

18:2, omega 6

Question 21

Arachidonic (ARA)

Answer 21

20:4, omega6

Question 22

FA storage

Answer 22

Glycerol + 3FAs = TG

Ester bond b/w COOH (FA) and OH (glycerol)

Middle FA = usually unsaturated

TGs stored primarily as fat droplets in the cytosol of adipocytes (less hydrated, less heavy, smaller than glycogen)

Question 23

Main functions of TGs

Answer 23

1. Long term energy storage in adipose and liver
2. Physical organ cushion (e.g. kidney)
3. Thermal insulation
4. Transport of fat soluble vitamins

Question 24

Nonshivering thermogenesis

Answer 24

Brown adipose

Color because of abundance of mitochondrial cytochromes

More metabolically active than white adipose

thermogenin = protein that uncouples the e-chain from ATP synthesis and this makes non-shivering heat
—>important for new-borns to maintain body temp.

Question 25

Cholecytokinin (CCK)

Answer 25

Secreted from intestinal mucosa in response to presence of lipids —> stimulates the gall bladder and pancreas to secrete their products

Question 26

Bile

Answer 26

Secreted by gall bladder in presence of CCK

Question 27

Enzymes secreted by pancrease

Answer 27

Pancreatic lipases Stimulated by CCK

Question 28

Steps of FA and TG digestion

Answer 28

1. Bile salts emulsify fats —> forming mixed MICELLES 2. TGs are degraded by the lipases to form fFAs and 2-monacylgylcerol 3. Lipid-soluble components (fat soluble vitamins etc) diffuse from the micelle into the mucosa of SI 4. FFAs converted back to TG 5. Mucosal cells package TGs, cholesterol and cholesteryl esters, phospholipids, and ApoB-48) into chylomicrons

Question 29

Chylomicrons

Answer 29

Apolipoprotein complex that transports dietary TGs to the peripheral cells Outer layer = phospholipids, cholesterol, and apolipoproteins (polar groups face aqueous environment) TGs = >80% of mass of cm

Question 30

Transport of TGs (in CM)

Answer 30

1. CM is released into the lymphatic system 2. Then into bloodstream for delivery to peripheral cells 3. ApoC-II activates lipoprotein lipase 4. Converts TGs —> fFAs and glycerol 5. FFAs enter peripheral cells, where they are converted back to TGs for storage (adipose) or oxidized for energy (muscle)

Question 31

Steatorrhea

Answer 31

Increase in lipids (especially FSVs and essential FAs) in the feces Caused by disturbance of lipid digestion and/or absorption E.g. cystic fibrosis can cause thickness in SI secretions and disrupts digestion Increasing short and medium FAs in the diet —> increase absorption rate of fat soluble vitamins and essential FAs

Question 32

Steps of synthesis of TGs

Answer 32

1. Glycerol-3P (G3P) formed 2. FA chain activated by Coenzyme A 3. First FA chain attached to C1 position of G3P by an ACYL TRANSFERASE 4. Process repeated to add a second carbon —> phosphatidic acid (PA) 5. Phosphate removed from by PA phosphatase —> 1,2-diacylglycerol (DAG) 6. Step 3 repeated to add third FA —> TGs

Question 33

Phosphatidic acid

Answer 33

Intermediate in TG synthesis (after second FA is added) Can also be used in phospholipid synthesis

Question 34

Liver Formation of G3P

Answer 34

1. Reduction of DHAP — by G3P dehydrogenase (needs NADH) —intermediate from glycolysis 2. Phosphorylating glycerol —by glycerol kinase (needs ATP)

Question 35

Adipose tissue Forming G3P

Answer 35

Only express G3P dehydrogenase...so can only do that pathway to make G3P to start TG synthesis Consequences for fasting state: Hydrolyze TG —> fFAs and glycerol —> which cannot be used later in the well-fed state Makes senses functionally because: 1. Fasting state —> inhibit reverse reaction of glycerol —> G3P...therefore FAs must leave the cell to be used elsewhere in the body for energy ... since TG synthesis has no backbone to add FAs to... 2. G3P will be generated when there is sufficient DHAP (well-fed) —> when TG storage is desirable

Question 36

Glucagon/Epinephrine cascade to mobilize adipose TGs

Answer 36

1. GPCR stimulated 2. Elicit a cAMP-dependent 2nd messenger 3. Stimulate PKA pathway 4. Phosphorylates hormone sensitive lipase and perilipin (to allow lipase to access the TGs in the fat droplets)

Question 37

Albumin

Answer 37

Protein that binds to fFAs to transport them in blood After they are released into blood from adipose after they are mobilized under glucagon/epi pathway

Question 38

Fate of fFAs that are not utilized by peripheral tissue after mobilized

Answer 38

Go to the liver —> repackaged into TGs Exported to the perpheral cells or stored back in the adipocytes

Question 39

Fate of glycerol when TGs are broken down in adipose tissue

Answer 39

Go to liver Fasting —> converted to glucose (gluconeogenesis) Well fed —> G3P by glycerol kinase for TG syn

Question 40

Hormonal regulation during well fed state

Answer 40

High insulin Stimulates synthesis and secretion of lipoprotein lipase —> hydrolyzes circulating TGs in CMs —> allows peripheral access to fFAs Liver —> fFAs —> TGs —> exported to peripheral Adipose —> fFAs —> TGs Inhibits hydrolysis of preexisting TGs in adipose

Question 41

Lipoprotein lipase Difference in response to insulin vs. glucagon/epinephrine Skeletal Muscle and cardiac

Answer 41

More stimulated via glucagoon/epinephrine than by insulin Makes sense because... In a well fed state —> muscles can derive their energy from glucose and store than energy as glycogen...hydrolysis and utilization of fFAs for energy is less needed for skeletal muscles cells Cardiac muscle —> gets most of energy from TGs and will use both glucose and fFAs as energy sources for muscle contraction

Question 42

Hormonal regulation in fasting state

Answer 42

Low insulin/high glucagon Muscle cells —> induce lipoprotein lipase to gain alternate fuel Adipose —> stimulated to hydrolyzes TGs, Liver —> produce glucose via gluconeo, use fFAs for energy, and also takes up fFAs in circulation —> TGs (to avoid too much fFAs in blood)