lecture 26: PUFA

Question 1

arachidonic acid (ARA)

Answer 1

most prominent n6 from a functional standpoint
primary substrate for eicosanoid synthesis > pro-inflammatory
signal transduction role from release of phospholipase A2

Question 2

PUFA (Polyunsaturated Fatty Acids)

Answer 2

hydrocarbon chains with 2 or more double bonds

Question 2

PUFA classes in food and body

Answer 2

n-6 and n-3 classes, methyl carbon is the 1 carbon, n designates double bond location

Question 3

linoleic acid

Answer 3

n-6 class, abundant in diet

Question 4

𝛂-Linolenic acid

Answer 4

n-3, structuraly similar to linoleic acid

Question 5

EPA, DHA

Answer 5

fish oil fatty acids
anti-inflammatory (n-3)

Question 6

synthesis of 20 and 22C PUFAs by humans

Answer 6

elongation (from 18C), desaturation, B-oxidation

n-3 and n-6 cannot be interconverted

Question 7

FA elongation (where does it occur, what happens)

Answer 7

occurs in the ER
elongase enzymes utilize n-6 and n-3 substrates and add carbons to CARBOXYL end
position of double bonds relative to methyl end remain the same
adds 2C at a time

Question 8

desaturation of FAs

Answer 8

occurs in ER, delta 5 and 6 desaturases use n-3 and n-6

Question 9

function of PUFA

Answer 9

1) lipid biomediators: regulators of inflammation, gene expression
2) membrane phospholipids: membrane functions

Question 10

function of n-6 PUFA

Answer 10

ligands for PPARs > gene expression
linoleic acid and ARA have membrane structural effects

Question 11

eicosanoids

Answer 11

synthesized from ARA, regulate many cellular functions
pro-or anti inflammatory signaling molecules
ratio based on n3/n6

Question 12

process of eicosanoid synthesis

Answer 12

binding of a hormone/cytokine (TNFa) to a membrane bound receptor > phospholipase A2 cleaves ARA from membrane phospholipid
epoxygenase, COX or LOX pathway converts ARA to eicosanoid

Question 13

prostaglandins

Answer 13

class of eicosanoids, produced by COX 1 or 2
pain, redness, swelling
induced by pro-inflammatory stimuli
COX enzymes are NSAID targets, active competitive inhibition

Question 14

prostaglandin E2 (PGE2)

Answer 14

involved in pain, redness, swelling

Question 15

EPA (eicosapentaenoic acid)

Answer 15

anti-inflammatory through competitive inhibition of ARA
compete for incorporation into plasma membrane > reduces ARA released by phospholipase A2

competes with ARA for metabolism > eicosanoids and resolvins

Question 16

resolvins

Answer 16

derived from EPA
reduce pro-inflammatory cytokines

Question 17

DHA

Answer 17

undergoes all three (elongation, desat, B-ox)
visual and cognitive functions

Question 18

process in which DNA enhances visual function

Answer 18

1) rhodopsin undergoes CC upon light
2) surrounding phospholipids including DHA facilitate CC
3) DHA increases rate of coupling to transducin

DHA increases phosphodiesterase activity

Question 19

3 transcription factors that bind lipids

Answer 19

PPARs, LXRs, SRBPs
PPAR and LXR can form heterodimers with RXR

Question 20

Why can’t humans produce n-3 PUFA from an n-6 substrate?

Answer 20

position of the double bonds relative to the methyl remain the same
we don’t have desaturase enzymes (introduce double bond) beyond delta 9 carbon

Question 21

in the process of converting linoleic acid (18:2) into arachidonic acid (20:4), two new double bonds have been introduced into the fatty acid. How is it that FADS1 and FADS2 can introduce double bonds at the ∆5 and ∆6 carbons, but the double bonds are not adjacent to each other?

Answer 21

carbons labelled relative to the carboxyl group
Elongase acts in between FADS1 and FADS2, two carbons are added to the carboxyl side which shifts the carbons’ numbered positions

elongation allows for saturated carbon in between, always adding 2

Question 22

Which group of compounds play an important role in the pain-signaling pathway? Which PUFA is a substrate for this pathway? How do aspirin and ibuprofen work to decrease pain?

Answer 22

Prostaglandins are produced from arachidonic acid and COX enzymes, mediate pain and inflammation

NSAIDS are competitive inhibitors to COX enzymes, inhibiting prostaglandin synthesis > reduce pain, inflammation

Question 23

Why is it important to maintain a healthy balance of omega-3 and omega-6 fatty acids? How is this balance reflected in eicosanoid production?

Answer 23

Omega-6: pro-inflammatory
eicosanoids (ARA)
Omega-3: produce anti-inflammatory compounds (EPA)

Competitive integration into membrane → both substrates to produce eicosanoids by COX enzymes, EPA also produces resolvins

Produce more of the inflammatory or anti-inflammatory eicosanoids based on n3/n6 ratio